1 00:00:05,560 --> 00:00:08,320 >>I'M NINA SCHOR, THE ACTING 2 00:00:08,320 --> 00:00:10,520 DEPUTY DIRECTOR FOR INTRAMURAL 3 00:00:10,520 --> 00:00:13,040 RESEARCH, AND IT TRULY IS MY 4 00:00:13,040 --> 00:00:15,880 PLEASURE TO LAUNCH THIS ACADEMIC 5 00:00:15,880 --> 00:00:18,360 YEAR'S NIH DIRECTOR'S SEMINAR 6 00:00:18,360 --> 00:00:19,240 SERIES. 7 00:00:19,240 --> 00:00:24,840 OUR SPEAKER THIS AFTERNOON IS 8 00:00:24,840 --> 00:00:27,560 DR. ANDREA APOLO FROM NCI. 9 00:00:27,560 --> 00:00:31,240 AS YOU KNOW, THE NIH DIRECTOR 10 00:00:31,240 --> 00:00:32,480 SEMINAR SERIES PRESENTS 11 00:00:32,480 --> 00:00:34,960 INVESTIGATORS WHO ARE NEWLY 12 00:00:34,960 --> 00:00:36,600 TENURED, AND WE ARE IN FOR A 13 00:00:36,600 --> 00:00:40,880 REAL TREAT THIS AFTERNOON. 14 00:00:40,880 --> 00:00:46,360 DR. APOLLO I APOLO IS AN INTERNATIONALLY 15 00:00:46,360 --> 00:00:48,440 RECOGNIZED RESEARCHER IN BLADDER 16 00:00:48,440 --> 00:00:49,400 CANCER RESEARCH. 17 00:00:49,400 --> 00:00:53,040 SHE GOT HER UNDERGRADUATE DEGREE 18 00:00:53,040 --> 00:00:57,600 SUMMA CUM LAUDE FROM LEHMAN 19 00:00:57,600 --> 00:00:58,800 COLLEGE, CITY UNIVERSITY IN 20 00:00:58,800 --> 00:01:00,400 NEW YORK, WITH A BACHELOR OF 21 00:01:00,400 --> 00:01:01,760 SCIENCE IN CHEMISTRY AND 22 00:01:01,760 --> 00:01:03,280 BIOCHEMISTRY. 23 00:01:03,280 --> 00:01:09,320 SHE THEN GOT HER MEDICAL DEGREE 24 00:01:09,320 --> 00:01:11,880 AT ALBERT EINSTEIN COLLEGE OF 25 00:01:11,880 --> 00:01:13,240 MEDICINE AND COMPLETED RESIDENCY 26 00:01:13,240 --> 00:01:15,720 TRAINING IN INTERNAL MEDICINE AT 27 00:01:15,720 --> 00:01:18,960 NEW YORK PRESBYTERIAN 28 00:01:18,960 --> 00:01:19,640 HOSPITAL/WEILL CORNEL MEDICAL 29 00:01:19,640 --> 00:01:21,360 CENTER IN NEW YORK CITY. 30 00:01:21,360 --> 00:01:24,280 SHE THEN WENT ON TO A MEDICAL 31 00:01:24,280 --> 00:01:27,400 ONCOLOGY FELLOWSHIP AT MEMORIAL 32 00:01:27,400 --> 00:01:28,360 SLOANE-KETTERING CANCER CENTER 33 00:01:28,360 --> 00:01:32,400 AND IN 2010 WAS RECRUITED TO THE 34 00:01:32,400 --> 00:01:33,160 NATIONAL CANCER INSTITUTE AND 35 00:01:33,160 --> 00:01:34,960 ITS PHYSICIAN-SCIENTIST EARLY 36 00:01:34,960 --> 00:01:36,480 INVESTIGATOR PROGRAM, 37 00:01:36,480 --> 00:01:38,440 SPECIFICALLY TO BUILD A 38 00:01:38,440 --> 00:01:39,200 TRANSLATIONAL BLADDER CANCER 39 00:01:39,200 --> 00:01:43,760 PROGRAM. 40 00:01:43,760 --> 00:01:47,880 DR. APOLO SERVES HERE AT NIH AS 41 00:01:47,880 --> 00:01:49,960 THE HEAD OF THE BLADDER CANCER 42 00:01:49,960 --> 00:01:56,160 SECTION OF THE GENITOURINARY 43 00:01:56,160 --> 00:01:57,400 MALIGNANCIES BRANCH AND THE 44 00:01:57,400 --> 00:02:02,800 DIRECTOR OF THE BLADDER CANCER 45 00:02:02,800 --> 00:02:05,200 JU TUMORS MULTIDISCIPLINARY 46 00:02:05,200 --> 00:02:05,440 CLINIC. 47 00:02:05,440 --> 00:02:07,360 SHE REALLY HAS BEEN INSTRUMENTAL 48 00:02:07,360 --> 00:02:08,440 IN BUILDING CLINICAL TRIALS THAT 49 00:02:08,440 --> 00:02:11,400 GO ALL THE WAY FROM FIRST IN 50 00:02:11,400 --> 00:02:15,800 HUMAN STUDIES THROUGH PHASE III 51 00:02:15,800 --> 00:02:16,480 CLINICAL TRIALS. 52 00:02:16,480 --> 00:02:18,760 SHE'S A PROLIFIC SPEAKER, 53 00:02:18,760 --> 00:02:21,760 MENTOR, AUTHOR. 54 00:02:21,760 --> 00:02:26,520 SHE HAS WON MANY, MANY AWARDS, 55 00:02:26,520 --> 00:02:31,200 BOTH HERE AT NIH AND NATIONALLY, 56 00:02:31,200 --> 00:02:32,200 INCLUDING THE 2020 ARTHUR S. 57 00:02:32,200 --> 00:02:34,600 FLEMMING AWARD FOR LEADERS WHO 58 00:02:34,600 --> 00:02:37,360 MAKE AN IMPACT IN PUBLIC 59 00:02:37,360 --> 00:02:37,560 SERVICE. 60 00:02:37,560 --> 00:02:43,160 SHE RECEIVED TENURE FROM NIH IN 61 00:02:43,160 --> 00:02:44,440 2021, AND IT'S WITH GREAT 62 00:02:44,440 --> 00:02:47,600 PLEASURE THAT I INTRODUCE 63 00:02:47,600 --> 00:02:56,120 DR. APOLO'S TALK ENTITLED: 64 00:02:56,120 --> 00:02:56,680 DEVELOPMENT OF TARGETED AND 65 00:02:56,680 --> 00:02:57,200 IMMUNE-BASED THEARPIES FOR 66 00:02:57,200 --> 00:02:57,800 UROTHELIAL CARCINOMAS AND RARE 67 00:02:57,800 --> 00:03:01,160 GENITOURINARY TUMORS. 68 00:03:01,160 --> 00:03:02,360 DR. APOLO, WELCOME. 69 00:03:02,360 --> 00:03:05,840 >> THANK YOU, DR. SCHOR, FOR 70 00:03:05,840 --> 00:03:07,360 THAT WONDERFUL INTRODUCTION. 71 00:03:07,360 --> 00:03:10,320 AND I'M ALSO VERY HONORED TO 72 00:03:10,320 --> 00:03:11,120 HAVE DR. GOTTESMAN ON THE LINE, 73 00:03:11,120 --> 00:03:12,840 WHO CAME ON A LITTLE EARLIER TOO 74 00:03:12,840 --> 00:03:13,960 TO SAY HELLO. 75 00:03:13,960 --> 00:03:16,960 SO THIS IS A TRUE HONOR TO BE 76 00:03:16,960 --> 00:03:19,640 HERE TODAY. 77 00:03:19,640 --> 00:03:22,040 I WANT TO TALK TODAY ABOUT DRUG 78 00:03:22,040 --> 00:03:23,040 DEVELOPMENT AND RESEARCH WITHIN 79 00:03:23,040 --> 00:03:25,360 OUR BLADDER CANCER PROGRAM AND 80 00:03:25,360 --> 00:03:27,960 OUR RARE G.U. TUMORS PROGRAM 81 00:03:27,960 --> 00:03:28,680 HERE AT THE NCI. 82 00:03:28,680 --> 00:03:32,520 BUT I WANTED TO START OFF BY 83 00:03:32,520 --> 00:03:33,840 ACKNOWLEDGING A PROGRAM THAT IS 84 00:03:33,840 --> 00:03:34,640 DEAR TO MY HEART. 85 00:03:34,640 --> 00:03:36,360 THIS IS THE NIH UNDERGRADUATE 86 00:03:36,360 --> 00:03:40,440 SCO LASCHOLARSHIP PROGRAM. 87 00:03:40,440 --> 00:03:41,680 I WOULDN'T BE WHERE I AM TODAY 88 00:03:41,680 --> 00:03:42,520 WITHOUT THIS PROGRAM. 89 00:03:42,520 --> 00:03:43,960 THIS PROGRAM WAS DEVELOPED FOR 90 00:03:43,960 --> 00:03:45,440 MINORITIES OF DISADVANTAGED 91 00:03:45,440 --> 00:03:46,200 BACKGROUNDS, AND THIS PROGRAM 92 00:03:46,200 --> 00:03:49,320 PROVIDED ME A SCHOLARSHIP DURING 93 00:03:49,320 --> 00:03:50,360 COLLEGE AND THE OPPORTUNITY TO 94 00:03:50,360 --> 00:03:51,320 WORK AT THE NIH. 95 00:03:51,320 --> 00:03:53,520 I WORKED HERE FOR THREE SUMMERS 96 00:03:53,520 --> 00:03:54,680 DURING COLLEGE THROUGH THIS 97 00:03:54,680 --> 00:03:56,120 PROGRAM, AND I WAS FIRST 98 00:03:56,120 --> 00:03:57,880 INTRODUCED TO BIOMEDICAL 99 00:03:57,880 --> 00:03:59,320 RESEARCH, AND MY LIFELONG 100 00:03:59,320 --> 00:04:00,480 COMMITMENT TO RESEARCH FIRST 101 00:04:00,480 --> 00:04:01,840 STARTED THROUGH THIS PROGRAM. 102 00:04:01,840 --> 00:04:03,240 SO I JUST WANTED TO START OFF 103 00:04:03,240 --> 00:04:06,200 WITH THAT ACKNOWLEDGMENT. 104 00:04:06,200 --> 00:04:07,920 AND NOW I'LL GO AHEAD AND START 105 00:04:07,920 --> 00:04:09,440 TALKING ABOUT BLADDER CANCER, 106 00:04:09,440 --> 00:04:11,120 AND I WANTED TO GIVE YOU A 107 00:04:11,120 --> 00:04:12,360 BACKGROUND ABOUT BLADDER CANCER 108 00:04:12,360 --> 00:04:14,840 JUST TO KIND OF PUT OUR RESEARCH 109 00:04:14,840 --> 00:04:17,000 INTO CONTEXT AND KIND OF WHERE 110 00:04:17,000 --> 00:04:20,000 IT FALLS INTO THE PARADIGM AND 111 00:04:20,000 --> 00:04:21,240 TREATMENTS OF BLADDER CANCER. 112 00:04:21,240 --> 00:04:23,080 BLADDER CANCER IS ACTUALLY A 113 00:04:23,080 --> 00:04:24,000 VERY COMMON CANCER IN THE UNITED 114 00:04:24,000 --> 00:04:28,520 STATES WITH AN ESTIMATED 81,000 115 00:04:28,520 --> 00:04:30,320 PATIENTS DIAGNOSED WITH BLADDER 116 00:04:30,320 --> 00:04:32,160 CANCER IN THE UNITED STATES THIS 117 00:04:32,160 --> 00:04:34,640 YEAR AND 17,000 PATIENTS WILL 118 00:04:34,640 --> 00:04:36,720 DIE WITH THIS DISEASE. 119 00:04:36,720 --> 00:04:38,160 THE MAJORITY OF THE TUMORS ARE 120 00:04:38,160 --> 00:04:41,760 LOCALIZED TO THE BLADDER AND 121 00:04:41,760 --> 00:04:43,200 MANAGED BY THE UROLOGIST, AND 122 00:04:43,200 --> 00:04:46,880 THERE IS A PREDOMINENCE O -- A 123 00:04:46,880 --> 00:04:50,040 MALE TO FEMALE PREDOMINENCE TO 124 00:04:50,040 --> 00:04:51,040 THE DEVELOPMENT OF BLADDER 125 00:04:51,040 --> 00:04:51,640 CANCER. 126 00:04:51,640 --> 00:04:53,360 FOR METASTATIC DISEASE, THE 127 00:04:53,360 --> 00:04:55,920 TREATMENT INCLUDES CHEMOTHERAPY, 128 00:04:55,920 --> 00:05:00,800 IMMUNOTHERAPY WITH CHECKPOINT 129 00:05:00,800 --> 00:05:04,400 INHIBITORS, ANTIBODY DRUG 130 00:05:04,400 --> 00:05:07,240 CONJUGATES, TYROSINE KIE NICE 131 00:05:07,240 --> 00:05:10,280 INHIBITOR TARGETING FGFR, BUT 132 00:05:10,280 --> 00:05:12,040 THE AVERAGE SURVIVAL IS 14 TO 20 133 00:05:12,040 --> 00:05:13,400 MONTHS, SO WE DEFINITELY HAVE A 134 00:05:13,400 --> 00:05:14,600 LOT OF ROOM FOR IMPROVEMENT IN 135 00:05:14,600 --> 00:05:16,520 TERMS OF THE TREATMENTS THAT WE 136 00:05:16,520 --> 00:05:17,920 OFFER OUR PATIENTS. 137 00:05:17,920 --> 00:05:19,520 THE RISK FACTORS FOR BLADDER 138 00:05:19,520 --> 00:05:20,960 CANCER ARE MANY. 139 00:05:20,960 --> 00:05:24,240 THE MAJORITY -- THE BIGGEST RISK 140 00:05:24,240 --> 00:05:27,200 FACTOR IS SMOKING. 141 00:05:27,200 --> 00:05:32,000 ANOTHER RISK FACTOR IS AROMATIC 142 00:05:32,000 --> 00:05:35,840 AMINES THAT ARE ASSOCIATED WITH 143 00:05:35,840 --> 00:05:37,360 CERTAIN OCCUPATIONS, LEATHER, 144 00:05:37,360 --> 00:05:42,840 RUBBER, PAINTING WITH ANALINE 145 00:05:42,840 --> 00:05:46,960 DYES, ALSO PRIOR PELVIC 146 00:05:46,960 --> 00:05:51,360 IRRADIATION, SCHISTOSOMIASIS, 147 00:05:51,360 --> 00:05:53,720 INDEMIC IN AFRICA, CAN LEAD TO 148 00:05:53,720 --> 00:05:56,040 SQUAMOUS SELL OR UROTHELIAL CELL 149 00:05:56,040 --> 00:05:57,640 CARCINOMA OF THE BLADDER. 150 00:05:57,640 --> 00:05:59,960 CHRONIC CYSTITIS, CHRONIC 151 00:05:59,960 --> 00:06:00,640 INFLAMMATION OF THE BLADDER IN 152 00:06:00,640 --> 00:06:02,920 PATIENTS THAT HAVE, FOR EXAMPLE, 153 00:06:02,920 --> 00:06:04,320 INDWELLING CATHETERS, PATIENTS 154 00:06:04,320 --> 00:06:06,720 THAT ARE PARAPLEGIC. 155 00:06:06,720 --> 00:06:09,880 IT CAN ALSO BE ASSOCIATED WITH 156 00:06:09,880 --> 00:06:12,960 LYNCH SYNDROME OR HNPCC, AND 157 00:06:12,960 --> 00:06:16,040 THIS IS GENERALLY UPPER TRACT 158 00:06:16,040 --> 00:06:16,960 TUMORS. 159 00:06:16,960 --> 00:06:19,600 SO PATIENTS OFTEN PRESENT WITH 160 00:06:19,600 --> 00:06:20,440 PAINLESS HEMATURIA OR BLOOD IN 161 00:06:20,440 --> 00:06:23,440 THE URINE, AND THEY UNDERGO A 162 00:06:23,440 --> 00:06:25,160 CYSTOSCOPIC EVALUATION BY THE 163 00:06:25,160 --> 00:06:25,440 UROLOGIST. 164 00:06:25,440 --> 00:06:27,520 AND THIS IS A LITTLE CAMERA TO 165 00:06:27,520 --> 00:06:29,640 TAKE A LOOK AT THE BLADDER, AND 166 00:06:29,640 --> 00:06:31,640 THERE COULD BE -- FROM THERE, 167 00:06:31,640 --> 00:06:34,160 THERE SHOULD BE A TRANS URETHRAL 168 00:06:34,160 --> 00:06:35,000 RESECTION OF THE BLADDER TUMOR 169 00:06:35,000 --> 00:06:36,960 THAT CAN BE DONE WHICH IS BOTH 170 00:06:36,960 --> 00:06:37,960 DIAGNOSTIC AND CAN BE 171 00:06:37,960 --> 00:06:39,920 THERAPEUTIC TOO. 172 00:06:39,920 --> 00:06:42,640 AND THEN WE STAGE -- ONCE WE GET 173 00:06:42,640 --> 00:06:45,160 THE TUMORS REMOVED, WE LOOK AT 174 00:06:45,160 --> 00:06:47,440 THEM UNDER THE MICROSCOPE AND WE 175 00:06:47,440 --> 00:06:49,200 STAGE THE GRADE OF THE TUMOR AND 176 00:06:49,200 --> 00:06:51,240 THE DEPTH OF INNOVATION. 177 00:06:51,240 --> 00:06:52,400 NON-MUSCLE INVASIVE BLADDER 178 00:06:52,400 --> 00:06:55,520 CANCER INCLUDES TA, T1 AND 179 00:06:55,520 --> 00:07:00,320 CARCINOMA IN SIGH TUT SITU, GENERALLY 180 00:07:00,320 --> 00:07:02,520 SCRAPING OR RESECTION. 181 00:07:02,520 --> 00:07:04,280 MUSCLE INVASIVE TUMORS, THESE 182 00:07:04,280 --> 00:07:07,640 INCLUDE T2, T3, T4 TUMORS, ARE 183 00:07:07,640 --> 00:07:09,480 REALLY MANAGED AS A 184 00:07:09,480 --> 00:07:10,800 MULTIDISCIPLINARY APPROACH WITH 185 00:07:10,800 --> 00:07:12,440 THE UROLOGIST, THE MEDICAL 186 00:07:12,440 --> 00:07:15,880 ONCOLOGIST, AND EVEN THE 187 00:07:15,880 --> 00:07:34,960 RADIATION BLADDER, 188 00:07:34,960 --> 00:07:37,240 THE URETER, THE RENAL PELVIS AND 189 00:07:37,240 --> 00:07:39,520 THE URETHRA. 190 00:07:39,520 --> 00:07:41,160 SO THIS SCHEMA HERE SUMMARIZES 191 00:07:41,160 --> 00:07:45,640 THE MANAGEMENT OF BLADDER CANCER 192 00:07:45,640 --> 00:07:46,760 PATIENTS BASED ON THEIR STAGE, 193 00:07:46,760 --> 00:07:49,680 AND IT DIVIDES IT BY NON-MUSCLE 194 00:07:49,680 --> 00:07:51,240 INVASIVE, MUSCLE INVASIVE AND 195 00:07:51,240 --> 00:07:51,640 METASTATIC DISEASE. 196 00:07:51,640 --> 00:07:56,440 SO LIKE I WAS MENTIONING BEFORE, 197 00:07:56,440 --> 00:07:57,640 NON-MUSCLE INVASIVE BLADDER 198 00:07:57,640 --> 00:07:59,240 CANCER IS PREDOMINANTLY MANAGED 199 00:07:59,240 --> 00:08:01,040 BY THE UROLOGIST WITH THE 200 00:08:01,040 --> 00:08:03,440 SCRAPINGS, THE TURBTs, AND 201 00:08:03,440 --> 00:08:06,080 THEN INTRAVESICAL THERAPY. 202 00:08:06,080 --> 00:08:07,840 THE INTRAVEST CAL THERAPY THAT 203 00:08:07,840 --> 00:08:09,920 IS MOST COMMONLY USED IS BCG, 204 00:08:09,920 --> 00:08:11,000 BUT OTHER CHEMOTHERAPIES ARE 205 00:08:11,000 --> 00:08:19,440 ALSO USED, AND THERE'S A LOT OF 206 00:08:19,440 --> 00:08:20,160 CLINICAL TRIALS CURRENTLY BEING 207 00:08:20,160 --> 00:08:21,120 DEVELOPED IN ORDER TO FIND 208 00:08:21,120 --> 00:08:22,080 BETTER TREATMENTS FOR PATIENTS 209 00:08:22,080 --> 00:08:24,920 THAT ARE BCG REFRACTORY TO 210 00:08:24,920 --> 00:08:25,920 PREVENT RECURRENCE AND 211 00:08:25,920 --> 00:08:29,000 PROGRESSIVE DISEASE. 212 00:08:29,000 --> 00:08:33,200 HERE AT THE NCI, WE HAVE TWO 213 00:08:33,200 --> 00:08:34,240 UROLOGICAL ONCOLOGISTS 214 00:08:34,240 --> 00:08:35,240 SPECIALIZING IN BLADDER CANCER 215 00:08:35,240 --> 00:08:36,280 WHO ARE ALSO WORKING ON 216 00:08:36,280 --> 00:08:37,720 DEVELOPING NEW THERAPIES FOR 217 00:08:37,720 --> 00:08:41,240 LOCALIZED DISEASE. 218 00:08:41,240 --> 00:08:43,080 SO NEXT I WANTED TO TALK ABOUT 219 00:08:43,080 --> 00:08:46,880 MUSCLE INVASIVE BLADDER CANCER, 220 00:08:46,880 --> 00:08:48,280 WHICH IS VERY AGGRESSIVE. 221 00:08:48,280 --> 00:08:49,160 THE PRIMARY TREATMENT IS YOU 222 00:08:49,160 --> 00:08:51,720 TAKE THE BLADDER OUT WITH A 223 00:08:51,720 --> 00:08:58,360 RADICAL SI STEC CYST STECT ME, ABOUT 224 00:08:58,360 --> 00:09:00,880 HALF OF THE TUMORS COME BACK 225 00:09:00,880 --> 00:09:01,200 METASTATIC. 226 00:09:01,200 --> 00:09:02,280 IN ORDER TO IMPROVE UPON THAT, 227 00:09:02,280 --> 00:09:04,920 WE HAVE INCORPORATED NEOADJUVANT 228 00:09:04,920 --> 00:09:06,840 TREATMENT AND EVEN ADJUVANT 229 00:09:06,840 --> 00:09:11,240 TREATMENT, SONN AND THIS IS WHY IT'S 230 00:09:11,240 --> 00:09:13,240 A MULTIDISCIPLINARY TUMOR AND WE 231 00:09:13,240 --> 00:09:18,480 OFTEN DISCUSS THESE PATIENTS 232 00:09:18,480 --> 00:09:20,320 WITH OUR UROLOGIC ONCOLOGY 233 00:09:20,320 --> 00:09:22,600 COLLEAGUES AND SOMETIMES 234 00:09:22,600 --> 00:09:23,960 RADIATION ONCOLOGY COLLEAGUES. 235 00:09:23,960 --> 00:09:26,200 SO PRIMARY TREATMENT IS A 236 00:09:26,200 --> 00:09:27,880 RADICAL CYSTECTOMY, NOT ONLY 237 00:09:27,880 --> 00:09:32,080 REMOVAL OF THE BLATTER BLADDER, IT ALSO 238 00:09:32,080 --> 00:09:35,080 INVOLVES REMOVING THE 239 00:09:35,080 --> 00:09:36,400 REGIONAL -- THE SEMINAL VESICLES 240 00:09:36,400 --> 00:09:37,840 AND THE PROXIMAL URETHRA. 241 00:09:37,840 --> 00:09:40,000 IN WOMEN, YOU REMOVE THE 242 00:09:40,000 --> 00:09:42,520 URETHRA, THE UTERUS, THE 243 00:09:42,520 --> 00:09:44,160 FALLOPIAN TUBES AND ANTERIOR 244 00:09:44,160 --> 00:09:45,440 VAGINAL WALL SO IT'S A VERY BIG 245 00:09:45,440 --> 00:09:45,920 SURGERY. 246 00:09:45,920 --> 00:09:46,800 THEN YOU RECONSTRUCT THE 247 00:09:46,800 --> 00:09:47,240 BLADDER. 248 00:09:47,240 --> 00:09:50,720 THERE'S A LOT OF DIRN WAY DIFFERENT WAYS 249 00:09:50,720 --> 00:09:52,360 OF DOING THAT, URINARY 250 00:09:52,360 --> 00:09:53,840 DIVERSIONS WE CALL THEM. 251 00:09:53,840 --> 00:09:59,360 THE MOST COMMON IS THE ILEAL 252 00:09:59,360 --> 00:10:04,680 CONDUIT, THE ILEAL CONDUIT, A 253 00:10:04,680 --> 00:10:06,320 PIECE OF THE BOWEL IS RESECTED, 254 00:10:06,320 --> 00:10:07,520 IS CUT OUT OF THE BOWEL AND THEN 255 00:10:07,520 --> 00:10:10,160 THE BOWEL IS REANASTOMOSED, AND 256 00:10:10,160 --> 00:10:11,920 THEN THE URETERS ARE ATTACHED TO 257 00:10:11,920 --> 00:10:14,640 THIS PIECE OF BOWEL AND THEN IT 258 00:10:14,640 --> 00:10:20,200 GETS ATTACHED TO THE ABDOMINAL 259 00:10:20,200 --> 00:10:21,920 CAVITY, THEN A STOMA IS FORMED 260 00:10:21,920 --> 00:10:23,120 AND AN OPENING RIGHT IN THE 261 00:10:23,120 --> 00:10:24,120 ABDOMINAL AREA AND THEN A BLAG 262 00:10:24,120 --> 00:10:28,680 IS PLACE -- ABAG IS PLACED THERE AND YOU H AVE 263 00:10:28,680 --> 00:10:29,400 CONTINUOUS FLOW OF URINE COMING 264 00:10:29,400 --> 00:10:35,920 FROM THE KIDNEYS INTO THE BAG. 265 00:10:35,920 --> 00:10:39,400 A CUTANEOUS CONTINENT RESERVOIR, 266 00:10:39,400 --> 00:10:40,520 SOMETIMES WE CALL THESE AN 267 00:10:40,520 --> 00:10:41,400 INDIANA POUCH. 268 00:10:41,400 --> 00:10:43,400 THESE ARE RESERVOIRS MADE FROM 269 00:10:43,400 --> 00:10:45,080 BOWEL AND THE PATIENT CAN 270 00:10:45,080 --> 00:10:46,120 CATHETERIZE THEMSELVES IN ORDER 271 00:10:46,120 --> 00:10:47,520 TO GET THE URINE OUT. 272 00:10:47,520 --> 00:10:53,640 AND THEN THERE'S A NEO BLADDER, 273 00:10:53,640 --> 00:10:56,440 USUALLY THE MOST HIGHLY SOUGHT 274 00:10:56,440 --> 00:10:58,000 BUT VERY HIGH MAINTENANCE IN 275 00:10:58,000 --> 00:11:01,360 THAT THE BOWEL, THE BOWEL POUCH 276 00:11:01,360 --> 00:11:03,560 IS ATTACHED TO THE NATIVE 277 00:11:03,560 --> 00:11:04,880 URETHRA. 278 00:11:04,880 --> 00:11:05,760 THIS CAN ONLY BE DONE IN 279 00:11:05,760 --> 00:11:07,160 PATIENTS WHERE WE KNOW THERE 280 00:11:07,160 --> 00:11:08,840 ISN'T ANY TUMOR IN THE URETHRA, 281 00:11:08,840 --> 00:11:10,360 SO THERE HAS TO BE A FROZEN 282 00:11:10,360 --> 00:11:11,840 SECTION DONE BY THE UROLOGIST 283 00:11:11,840 --> 00:11:14,360 DURING THE SURGERY, AND THEN THE 284 00:11:14,360 --> 00:11:15,840 BOWEL IS ATTACHED TO THE 285 00:11:15,840 --> 00:11:17,880 URETHRA, AND THE PATIENT 286 00:11:17,880 --> 00:11:20,120 URINATES AS IF THEY HAD A NATIVE 287 00:11:20,120 --> 00:11:24,280 BLADDER THROUGH THEIR URETHRA. 288 00:11:24,280 --> 00:11:25,400 SO WITH THAT BACKGROUND, I 289 00:11:25,400 --> 00:11:27,120 WANTED TO MOVE ON TO TALK ABOUT 290 00:11:27,120 --> 00:11:28,480 OUR NCI BLADDER CANCER PROGRAM, 291 00:11:28,480 --> 00:11:32,920 AND WE HAVE A LOT OF STUDIES OF 292 00:11:32,920 --> 00:11:38,600 BOTH PRE-CLINICAL, AND CLINICAL 293 00:11:38,600 --> 00:11:40,240 AND I BROKE IT DOWN INTO THREE 294 00:11:40,240 --> 00:11:43,440 RESEARCH AIMS JUST TO KIND OF 295 00:11:43,440 --> 00:11:45,400 ORGANIZE IT AND FOCUS ON THE 296 00:11:45,400 --> 00:11:46,800 PROGRAM THIS WAY. 297 00:11:46,800 --> 00:11:48,880 SO THE FIRST AIM IS TO DEVELOP 298 00:11:48,880 --> 00:11:50,640 TARGETED AND IMMUNE-BASED 299 00:11:50,640 --> 00:11:51,640 THERAPIES AGAINST MUSCLE 300 00:11:51,640 --> 00:11:54,880 INVASIVE AND METASTATIC 301 00:11:54,880 --> 00:11:56,200 UROTHELIAL CARCINOMA WITH A 302 00:11:56,200 --> 00:11:58,040 FOCUS ON TYROSINE KINASE 303 00:11:58,040 --> 00:11:59,440 INHIBITORS AND COMBINATION 304 00:11:59,440 --> 00:11:59,720 STRATEGIES. 305 00:11:59,720 --> 00:12:02,520 THE SECOND AIM IS TO DEVELOP 306 00:12:02,520 --> 00:12:07,880 PROGRESS MOSGNOSTIC BIOMARKERS RECEIVING 307 00:12:07,880 --> 00:12:09,440 THESE THERAPIES, BOTH TARGETED 308 00:12:09,440 --> 00:12:10,640 AND IMMUNE BASED THERAPIES. 309 00:12:10,640 --> 00:12:13,040 AND THE THIRD IS TO IDENTIFY 310 00:12:13,040 --> 00:12:15,760 EFFECTIVE THERAPIES FOR ADVANCED 311 00:12:15,760 --> 00:12:19,200 METASTATIC RARE BLADDER TUMORS, 312 00:12:19,200 --> 00:12:33,280 SUCH AS URACHAL/ADENOCARCINOMA 313 00:12:33,280 --> 00:12:35,240 AND OTHER RARE G.U. TUMORS. 314 00:12:35,240 --> 00:12:38,000 AND THE OVERARCHING HIGH 315 00:12:38,000 --> 00:12:39,000 POTASSIUM THESE WITH THESE AIMS 316 00:12:39,000 --> 00:12:40,880 IS THE DETAILED UNDERSTANDING OF 317 00:12:40,880 --> 00:12:42,240 THE MAJOR DISEASE DRIVERS AND 318 00:12:42,240 --> 00:12:44,320 IMMUNE MODULATION BY ACTIVE 319 00:12:44,320 --> 00:12:47,080 THERAPEUTIC AGENTS WILL RESULT 320 00:12:47,080 --> 00:12:48,480 IN THE IDENTIFICATION OF 321 00:12:48,480 --> 00:12:51,640 EFFECTIVE TREATMENTS AND 322 00:12:51,640 --> 00:12:53,440 BIOMARKER STRATEGIES FOR THESE 323 00:12:53,440 --> 00:12:53,720 TUMORS. 324 00:12:53,720 --> 00:12:57,320 SO WHEN I WAS A FELLOW AT 325 00:12:57,320 --> 00:12:58,760 SLOANE-KETTERING, I DID A COUPLE 326 00:12:58,760 --> 00:13:02,600 TRIALS WITH AGENTS AND WE WERE 327 00:13:02,600 --> 00:13:03,960 SEEING SOME VERY NICE EFFICACY, 328 00:13:03,960 --> 00:13:06,680 SO WHEN I CAME UP TO THE NIH 329 00:13:06,680 --> 00:13:10,560 ABOUT 12, ALMOST 13 YEARS AGO, I 330 00:13:10,560 --> 00:13:13,960 COLLABORATED WITH DR. DON 331 00:13:13,960 --> 00:13:17,880 BOTTARO, WHO ALSO HAD AN 332 00:13:17,880 --> 00:13:19,160 INTEREST IN SMALL MOLECULE 333 00:13:19,160 --> 00:13:20,880 INHIBITORS OF MULTIPLE TYROSINE 334 00:13:20,880 --> 00:13:24,760 KINASES, AND WE STUDIED MULTIPLE 335 00:13:24,760 --> 00:13:27,920 DIFFERENT AGENT AND STARTED 336 00:13:27,920 --> 00:13:32,920 STUDYING CABOZANTINIB WAS ONE OF 337 00:13:32,920 --> 00:13:40,840 THEM. 338 00:13:40,840 --> 00:13:43,440 LIKE I SAID I DID WORK WITH 339 00:13:43,440 --> 00:13:44,800 OTHER TARGETED VEGF AGENTS AND 340 00:13:44,800 --> 00:13:47,280 WE SAW SOME NICE ACTIVITY, 341 00:13:47,280 --> 00:13:50,560 PRE-CLINICAL ACTIVITY AND WERE 342 00:13:50,560 --> 00:13:55,600 WONDERING WHICH TARGET IS THE 343 00:13:55,600 --> 00:13:59,440 MOST IMPORTANT AND DR. BOTTARO 344 00:13:59,440 --> 00:14:03,360 HAS STRONG INTEREST IN MET, THAT 345 00:14:03,360 --> 00:14:06,640 LEADS TO MULTIPLE CYTOKINE 346 00:14:06,640 --> 00:14:10,800 ACTIVATIONS INVOLVE IN 347 00:14:10,800 --> 00:14:11,120 TUMORIGENESIS. 348 00:14:11,120 --> 00:14:13,320 SO IN COLLABORATION WITH 349 00:14:13,320 --> 00:14:14,640 DR. BOTTARO, WE WORKED ON 350 00:14:14,640 --> 00:14:15,920 SEVERAL PRE-CLINICAL STUDIES AND 351 00:14:15,920 --> 00:14:19,400 FOUND WITHIN OUR BLADDER CANCER 352 00:14:19,400 --> 00:14:22,840 CELL PROTEINS THAT MET PROTEIN 353 00:14:22,840 --> 00:14:24,200 WAS HIGHER THAN THOSE DERIVED 354 00:14:24,200 --> 00:14:26,760 FROM HIGHER STAGE AND CELL LINES 355 00:14:26,760 --> 00:14:28,600 RESPONDED TO HGT FIM STIMULATION 356 00:14:28,600 --> 00:14:30,200 WITH INCREASED ACTIVATION OF 357 00:14:30,200 --> 00:14:33,160 DOWNSTREAM SIGNALING PATHWAYS, 358 00:14:33,160 --> 00:14:35,960 PI3K AND MAPK AND THAT 359 00:14:35,960 --> 00:14:38,720 CABOZANTINIB REVERSES 360 00:14:38,720 --> 00:14:39,600 HGF/MET-MEDIATED ACTIVATION. 361 00:14:39,600 --> 00:14:42,040 WE CONFIRMED THESE EXPERIMENTS 362 00:14:42,040 --> 00:14:44,840 USING SPECIAL HGF KNOCK-IN SCID 363 00:14:44,840 --> 00:14:48,320 MICE AND FOUND THAT CABOZANTINIB 364 00:14:48,320 --> 00:14:49,440 DECREASED TUMOR GROWTH OF THE 365 00:14:49,440 --> 00:14:50,200 BLADDER CANCER. 366 00:14:50,200 --> 00:14:51,440 SO THIS WAS VERY EXCITING AND 367 00:14:51,440 --> 00:14:53,040 THIS WAS OUR RATIONALE FOR 368 00:14:53,040 --> 00:14:55,640 INITIATING A CLINICAL TRIAL FOR 369 00:14:55,640 --> 00:14:57,160 PATIENTS WITH ADVANCED BLADDER 370 00:14:57,160 --> 00:14:57,400 CANCER. 371 00:14:57,400 --> 00:15:00,360 THIS WAS FOR PATIENTS THAT WERE 372 00:15:00,360 --> 00:15:03,440 REFRACTORY TO CHEMOTHERAPY, I 373 00:15:03,440 --> 00:15:07,440 INITIATED A PHASE 2 STUDY OF 374 00:15:07,440 --> 00:15:08,320 MODEL THERAPY CABOZANTINIB IN 375 00:15:08,320 --> 00:15:08,920 THESE PATIENTS. 376 00:15:08,920 --> 00:15:10,040 I INCLUDED PATIENTS NOT ONLY 377 00:15:10,040 --> 00:15:12,280 WITH METASTATIC BLADDER CANCER 378 00:15:12,280 --> 00:15:15,320 THAT ALREADY RECEIVED 379 00:15:15,320 --> 00:15:18,640 CHEMOTHERAPY, BUT ALSO PATIENTS 380 00:15:18,640 --> 00:15:20,280 WITH BONE -- DISEASE. 381 00:15:20,280 --> 00:15:21,640 YOU CAN'T MEASURE THEIR TUMORS, 382 00:15:21,640 --> 00:15:24,120 WE DON'T HAVE GOOD IMAGING 383 00:15:24,120 --> 00:15:25,560 MODALITY TO MEASURE THE QUANTITY 384 00:15:25,560 --> 00:15:28,840 AND THE RESPONSE OF THE TUMORS 385 00:15:28,840 --> 00:15:29,240 IN THE BONE. 386 00:15:29,240 --> 00:15:32,640 SO I INCLUDED AN EXPLORATORY 387 00:15:32,640 --> 00:15:34,280 COHORT OF BONE-ONLY DISEASE AND 388 00:15:34,280 --> 00:15:36,240 ALSO AN EXPLORATORY COHORT OF 389 00:15:36,240 --> 00:15:39,080 PATIENTS WITH RARE BLADDER 390 00:15:39,080 --> 00:15:40,280 HISTOLOGIES BECAUSE WE HAVE A 391 00:15:40,280 --> 00:15:43,800 HIGH REFERRAL PATTERN HERE AT 392 00:15:43,800 --> 00:15:45,000 THE NIH AND WE WANTED TO LEARN 393 00:15:45,000 --> 00:15:46,640 MORE ABOUT THESE THERAPIES IN 394 00:15:46,640 --> 00:15:48,720 THESE RARE TUMORS. 395 00:15:48,720 --> 00:15:50,880 IMOWN SO WE REPORTED THE RESULTS 396 00:15:50,880 --> 00:15:53,680 OF THIS PHASE TWO STUDY OF 397 00:15:53,680 --> 00:15:56,360 MONOTHERAPY CABOZANTINIB AND WE 398 00:15:56,360 --> 00:15:58,240 FOUND AN OVERALL RESPONSE RATE 399 00:15:58,240 --> 00:15:59,640 OF 19%, WHICH WAS PRETTY 400 00:15:59,640 --> 00:16:01,720 EXCITING IN PATIENTS THAT WERE 401 00:16:01,720 --> 00:16:04,040 REFRACTORY TO CHEMOTHERAPY. 402 00:16:04,040 --> 00:16:06,440 AND WE ALSO SAW RESPONSES IN THE 403 00:16:06,440 --> 00:16:08,240 BONE, AND THAT WAS VERY 404 00:16:08,240 --> 00:16:08,720 EXCITING. 405 00:16:08,720 --> 00:16:13,200 THESE ARE SODIUM CHLORIDE, 406 00:16:13,200 --> 00:16:14,160 PATIENTS WITH BONE DISEASE AND 407 00:16:14,160 --> 00:16:15,920 THE SPOTS THERE ARE TUMORS THAT 408 00:16:15,920 --> 00:16:17,640 YOU SEE IN THE PATIENTS AND THEN 409 00:16:17,640 --> 00:16:19,480 THERE'S THE PRE AND THE POST AND 410 00:16:19,480 --> 00:16:22,640 THESE ARE THREE DIFFERENT 411 00:16:22,640 --> 00:16:24,080 PATIENTS PRE-TREATMENT AND THEN 412 00:16:24,080 --> 00:16:24,960 POST TREATMENT WITH 413 00:16:24,960 --> 00:16:26,160 CABOZANTINIB, WE SEE IMPROVEMENT 414 00:16:26,160 --> 00:16:27,960 IN THE SODIUM FLUORIDE IN THESE 415 00:16:27,960 --> 00:16:28,240 PATIENTS. 416 00:16:28,240 --> 00:16:31,120 AND WE DID THIS IN COLLABORATION 417 00:16:31,120 --> 00:16:33,240 WITH THE MOLECULAR IMAGING 418 00:16:33,240 --> 00:16:44,200 BRANCH, FOR THE PET SCAN STUDY. 419 00:16:44,200 --> 00:16:46,480 IN CORRELATIVE STUDIES, I HAVE A 420 00:16:46,480 --> 00:16:49,440 TERRIFIC COLLABORATION WITH JANE 421 00:16:49,440 --> 00:16:50,960 TREPELL'S LAB, WE FOUND THAT 422 00:16:50,960 --> 00:16:53,560 CABOZANTINIB MODULATED PRIF LAL 423 00:16:53,560 --> 00:16:54,600 BLOOD-IMMUNE SUBSETS INCLUDING 424 00:16:54,600 --> 00:16:56,320 DECREASING CLASSICAL MONOCYTES 425 00:16:56,320 --> 00:16:59,920 WHICH ARE PRO TEUM ROWGENIC, 426 00:16:59,920 --> 00:17:01,440 INCLUDES THOSE THAT HAVE 427 00:17:01,440 --> 00:17:02,640 ANTITUMOR ACTIVITY WHILE 428 00:17:02,640 --> 00:17:06,800 MAINTAINING THE RATIO OF 429 00:17:06,800 --> 00:17:07,600 CT8 CELLS TO T REGS. 430 00:17:07,600 --> 00:17:09,760 IN GENERAL, WE SAW CABOZANTINIB 431 00:17:09,760 --> 00:17:11,800 HAS IMMUNOMODULATORY PROPERTIES 432 00:17:11,800 --> 00:17:14,320 OF BOTH IMMUNOSTIMULATORY CELLS 433 00:17:14,320 --> 00:17:17,840 AND IMMUNOSUPPRESSIVE CELLS. 434 00:17:17,840 --> 00:17:20,280 AND THESE PROPERTY MAY, WE 435 00:17:20,280 --> 00:17:22,080 HYPOTHESIZE, MAY INTERACT TUMOR 436 00:17:22,080 --> 00:17:24,440 SUPPRESSION AND IT PROVIDED US A 437 00:17:24,440 --> 00:17:25,800 RATIONALE FOR COMBINING 438 00:17:25,800 --> 00:17:27,440 CABOZANTINIB WITH AN 439 00:17:27,440 --> 00:17:28,520 IMMUNOTHERAPY SUCH AS A 440 00:17:28,520 --> 00:17:29,320 CHECKPOINT INHIBITOR. 441 00:17:29,320 --> 00:17:33,960 AT THE SAME TIME, I WAS RUNNING 442 00:17:33,960 --> 00:17:35,400 PHASE ONE TRIALS WITH CHECKPOINT 443 00:17:35,400 --> 00:17:36,920 INHIBITORS AND SAW REMARKABLE 444 00:17:36,920 --> 00:17:38,360 ACTIVITY WITH CHECKPOINT 445 00:17:38,360 --> 00:17:39,280 INHIBITORS AND IT JUST MADE 446 00:17:39,280 --> 00:17:40,960 SENSE TO COMBINE THESE TWO 447 00:17:40,960 --> 00:17:42,840 AGENTS AS THEY WERE BOTH ACTIVE. 448 00:17:42,840 --> 00:17:47,640 SO I INITIATED A PHASE ONE TRIAL 449 00:17:47,640 --> 00:17:57,800 OF CABOZANTINIB DOUBLET PLUS 450 00:17:57,800 --> 00:18:01,440 NIVOLUMAB AND IPILIMUMAB SO WE 451 00:18:01,440 --> 00:18:03,800 WERE LOOKING FOR A SAFE DOSE FOR 452 00:18:03,800 --> 00:18:09,480 THE DUB LE DOUBLET AND THE TRIP LET. 453 00:18:09,480 --> 00:18:10,880 WE LOOKED AT EIGHT DIFFERENT 454 00:18:10,880 --> 00:18:11,920 ESCALATING DOSES AND WE 455 00:18:11,920 --> 00:18:16,920 PUBLISHED THIS IN JCO AND THIS 456 00:18:16,920 --> 00:18:19,920 WAS A VERY HETEROGENEOUS GROUP 457 00:18:19,920 --> 00:18:20,240 OF PATIENTS. 458 00:18:20,240 --> 00:18:21,960 IT INCLUDED PATIENTS WITH 459 00:18:21,960 --> 00:18:24,000 BLADDER CANCER, KIDNEY CANCER, 460 00:18:24,000 --> 00:18:26,600 PROSTATE CANCER, GERM CELL 461 00:18:26,600 --> 00:18:28,520 TUMORS, AND RARE G.U. TUMORS, 462 00:18:28,520 --> 00:18:30,520 AND PATIENTS WITH VERY ADVANCED 463 00:18:30,520 --> 00:18:34,040 DISEASE, 80% OF THEM HAD 464 00:18:34,040 --> 00:18:36,880 VISCERAL METASTASES INCLUDING 465 00:18:36,880 --> 00:18:38,280 BONE, LIVER OR LUNG DISEASE. 466 00:18:38,280 --> 00:18:40,480 THESE ARE THE RESULTS. 467 00:18:40,480 --> 00:18:42,240 WE SAW SOME VERY NICE RESPONSES 468 00:18:42,240 --> 00:18:45,720 WITH THE DOUBLET AND TRIPLET 469 00:18:45,720 --> 00:18:46,160 THERAPY. 470 00:18:46,160 --> 00:18:49,200 THIS IS THE WATERFALL PLOT, WE 471 00:18:49,200 --> 00:18:51,480 SAW AN OVERALL RESPONSE RATE OF 472 00:18:51,480 --> 00:18:52,920 31% IN THIS HETEROGENEOUS GROUP 473 00:18:52,920 --> 00:18:53,360 OF PATIENTS. 474 00:18:53,360 --> 00:18:54,840 SO THAT WAS VERY EXCITING, AND 475 00:18:54,840 --> 00:18:56,760 ONE OF THE THINGS ABOUT IT IS 476 00:18:56,760 --> 00:18:59,400 THESE RESPONSES WERE DURABLE. 477 00:18:59,400 --> 00:19:03,440 THIS STUDY WAS INITIATED IN 478 00:19:03,440 --> 00:19:04,960 EARLY 2015, AND I HAD PATIENTS 479 00:19:04,960 --> 00:19:07,520 THAT ARE STILL COMING BACK TO 480 00:19:07,520 --> 00:19:08,880 CLINIC NOW, SEVEN YEARS LATER, 481 00:19:08,880 --> 00:19:09,760 IN FOLLOW-UP. 482 00:19:09,760 --> 00:19:12,400 SO PATIENTS THAT RESPOND 483 00:19:12,400 --> 00:19:14,240 ACTUALLY RESPOND REALLY WELL AND 484 00:19:14,240 --> 00:19:17,520 THE RESPONSES ARE DURABLE FNLT 485 00:19:17,520 --> 00:19:19,480 SO THIS WAS VERY EXCITING TO US. 486 00:19:19,480 --> 00:19:21,040 AND WE EXPANDED THE PHASE ONE 487 00:19:21,040 --> 00:19:22,360 BECAUSE WE SAW THE ACTIVITY IN 488 00:19:22,360 --> 00:19:24,840 THE FIRST 54 PATIENTS, WE 489 00:19:24,840 --> 00:19:26,840 EXPANDED IT INTO MULTIPLE 490 00:19:26,840 --> 00:19:28,800 DIFFERENT COHORTS IN BLADDER 491 00:19:28,800 --> 00:19:31,040 CANCER AND KIDNEY CAN SE WE 492 00:19:31,040 --> 00:19:34,800 LOOKED AT ADENOCARCINOMA, 493 00:19:34,800 --> 00:19:36,800 URECHAL, SQUAMOUS CARCINOMA OF 494 00:19:36,800 --> 00:19:40,240 THE BLADDER, WE LOOKED AT PENILE 495 00:19:40,240 --> 00:19:42,080 CANCER, AND WE ALSO HAD A SMALL 496 00:19:42,080 --> 00:19:42,760 COHORT, ABOUT 30 PATIENTS THAT I 497 00:19:42,760 --> 00:19:46,240 WANT TO HIGHLIGHT, THAT 498 00:19:46,240 --> 00:19:47,680 PREVIOUSLY HAD CHECKPOINT 499 00:19:47,680 --> 00:19:50,640 INHIBITOR AND HAD PROGRESSED. 500 00:19:50,640 --> 00:19:53,200 AND WE SAW IN -- THIS IS 30 501 00:19:53,200 --> 00:19:54,800 PATIENTS, WE SAW A RESPONSE RATE 502 00:19:54,800 --> 00:19:56,440 IN FOUR OF THESE PATIENTS THAT 503 00:19:56,440 --> 00:19:57,840 WERE PRETTY REMARKABLE. 504 00:19:57,840 --> 00:19:59,680 SO THESE PATIENTS, AGAIN, HAD 505 00:19:59,680 --> 00:20:02,920 ALREADY HAD CHECKPOINT AND THEY 506 00:20:02,920 --> 00:20:03,840 RESPONDED, AND WE PUBLISHED 507 00:20:03,840 --> 00:20:07,880 THIS, THIS IS MY FELLOW, 508 00:20:07,880 --> 00:20:09,480 DR. GIRARDI, WHO PUBLISHED AS 509 00:20:09,480 --> 00:20:11,480 FIRST AUTHOR THIS MANUSCRIPT, 510 00:20:11,480 --> 00:20:12,760 AND THESE RESPONSES WERE VERY 511 00:20:12,760 --> 00:20:13,000 DURABLE. 512 00:20:13,000 --> 00:20:16,240 I MEAN, THEY LASTED FOR A VERY 513 00:20:16,240 --> 00:20:18,240 LONG TIME. 514 00:20:18,240 --> 00:20:21,280 HERE I HAVE A CAT SCAN OF A 515 00:20:21,280 --> 00:20:23,880 PATIENT AT BAS BASELINE, YOU CAN SEE 516 00:20:23,880 --> 00:20:26,160 THESE TUMORS THAT THE ARROW IS 517 00:20:26,160 --> 00:20:28,400 POINTING AT, THOSE ARE LARGE 5, 518 00:20:28,400 --> 00:20:29,840 6 CENTIMETER TUMORS IN THE LUNG, 519 00:20:29,840 --> 00:20:37,200 THE PATIENT HAD TO HAVE NINE 520 00:20:37,200 --> 00:20:39,720 MONTHS OF -- WE PUT HER ON THE 521 00:20:39,720 --> 00:20:41,560 CABO AP NIVO COMBINATION AND SHE 522 00:20:41,560 --> 00:20:43,600 JUST HAD A REMARKABLE RESPONSE, 523 00:20:43,600 --> 00:20:45,000 VERY DURABLE FOR SEVERAL YEARS, 524 00:20:45,000 --> 00:20:47,200 THE CANCER NEVER CAME BACK IN 525 00:20:47,200 --> 00:20:50,240 THE LUNGS, ACTUALLY WHEN IT DID 526 00:20:50,240 --> 00:20:51,800 COME BACK, IT CAME BACK -- 527 00:20:51,800 --> 00:20:54,280 RECENTLY IT CAME BACK IN THE 528 00:20:54,280 --> 00:20:55,400 BRAIN. 529 00:20:55,400 --> 00:20:56,400 WHICH IS A SANCTUARY SITE. 530 00:20:56,400 --> 00:20:58,120 SO THE PATIENT DID PASS AWAY 531 00:20:58,120 --> 00:20:59,560 RECENTLY WITH BRAIN METASTASES. 532 00:20:59,560 --> 00:21:00,960 BUT THE CANCER NEVER CAME BACK 533 00:21:00,960 --> 00:21:02,160 IN THE LUNG, WHICH WAS VERY 534 00:21:02,160 --> 00:21:07,520 INTERESTING. 535 00:21:07,520 --> 00:21:10,680 I WANTED TO HIGHLIGHT 536 00:21:10,680 --> 00:21:12,000 DR. BERNADETTE RETT, SHE'S IN 537 00:21:12,000 --> 00:21:13,240 THE CLINICAL CENTER IN THE 538 00:21:13,240 --> 00:21:14,640 RADIOLOGY DEPARTMENT, AND SHE 539 00:21:14,640 --> 00:21:15,600 HELPS US MEASURE THESE LESIONS 540 00:21:15,600 --> 00:21:17,680 ON A WEEKLY BASIS ON PATIENTS 541 00:21:17,680 --> 00:21:20,240 THAT ARE UNDERGOING TREATMENT 542 00:21:20,240 --> 00:21:21,440 WITHIN THESE CLINICAL TRIALS AND 543 00:21:21,440 --> 00:21:23,440 WE'RE VERY GRATEFUL TO HER AND 544 00:21:23,440 --> 00:21:31,960 ALL HER HELP, AND ALSO OTHERS 545 00:21:31,960 --> 00:21:33,400 WHO COME TO OUR 546 00:21:33,400 --> 00:21:34,600 MULTIDISCIPLINARY CLINIC THAT IS 547 00:21:34,600 --> 00:21:36,240 RUN WEEKLY, WHERE WE REVIEW 548 00:21:36,240 --> 00:21:38,200 THESE SCANS, WE REVIEW PATHOLOGY 549 00:21:38,200 --> 00:21:41,320 AND WE DISCUSS COMPLICATED 550 00:21:41,320 --> 00:21:42,840 PATIENTS WITH IN THE 551 00:21:42,840 --> 00:21:43,760 MULTIDISCIPLINARY APPROACH WITH 552 00:21:43,760 --> 00:21:47,640 UROLOGISTS AND RADIATION 553 00:21:47,640 --> 00:21:47,960 ONCOLOGISTS. 554 00:21:47,960 --> 00:21:49,760 SO I'M VERY GRATEFUL TO THEM FOR 555 00:21:49,760 --> 00:21:53,480 ALL THEIR HELP. 556 00:21:53,480 --> 00:21:55,200 SO WE HAD MULTIPLE EXPANSION 557 00:21:55,200 --> 00:21:55,480 COHORTS. 558 00:21:55,480 --> 00:21:59,720 WE ENROLLED 150 PATIENTS TO THE 559 00:21:59,720 --> 00:22:00,800 STUDY, AND I PRESENTED THE 560 00:22:00,800 --> 00:22:02,320 RESULTS, SO WE ALREADY PUBLISHED 561 00:22:02,320 --> 00:22:03,320 THE 30 PATIENTS THAT WERE 562 00:22:03,320 --> 00:22:05,640 PREVIOUSLY TREATED. 563 00:22:05,640 --> 00:22:07,400 I PRESENTED THE RESULTS OF THE 564 00:22:07,400 --> 00:22:14,240 120 PATIENTS THAT WERE 565 00:22:14,240 --> 00:22:15,040 IMMUNOTHERAPY-NAIVE AS AN ORAL 566 00:22:15,040 --> 00:22:15,920 PRESENTATION AND THE RESPONSES 567 00:22:15,920 --> 00:22:17,520 WERE JUST REMARKABLE. 568 00:22:17,520 --> 00:22:19,640 WE SAW AN OVERALL RESPONSE RATE 569 00:22:19,640 --> 00:22:21,400 OF 38% WITH 11% COMPLETE 570 00:22:21,400 --> 00:22:23,160 RESPONSE IN THIS, AGAIN, VERY 571 00:22:23,160 --> 00:22:25,000 HETEROGENEOUS GROUP OF PATIENTS 572 00:22:25,000 --> 00:22:25,640 WITH G.U. TUMORS. 573 00:22:25,640 --> 00:22:28,440 SO BLADDER, KIDNEY, PROSTATE, 574 00:22:28,440 --> 00:22:32,040 GERM CELL, AND RARE GENE TUMORS. 575 00:22:32,040 --> 00:22:33,640 AND WE BROKE IT DOWN BY TUMOR 576 00:22:33,640 --> 00:22:33,840 TYPE. 577 00:22:33,840 --> 00:22:35,600 SO WHEN WE LOOKED AT THE KIDNEY 578 00:22:35,600 --> 00:22:37,800 TUMORS, WE SAW A RESPONSE RATE 579 00:22:37,800 --> 00:22:41,440 OF 63%, WHICH WAS REALLY, REALLY 580 00:22:41,440 --> 00:22:42,040 HIGH. 581 00:22:42,040 --> 00:22:44,880 AND BASED ON THE KIDNEY CANCER 582 00:22:44,880 --> 00:22:48,640 DATA, WE WENT ON TO A PHASE 3, 583 00:22:48,640 --> 00:22:50,360 SO EXCITED BY THIS DATA THEY 584 00:22:50,360 --> 00:22:51,920 LAUNCHED A PHASE III STUDY IN 585 00:22:51,920 --> 00:22:53,200 KIDNEY CANCER BASED ON OUR PHASE 586 00:22:53,200 --> 00:22:54,920 ONE STUDY, AND IN BLADDER 587 00:22:54,920 --> 00:22:56,040 CANCER, WE SAW AN OVERALL 588 00:22:56,040 --> 00:22:58,040 RESPONSE RATE OF 42% WITH HALF 589 00:22:58,040 --> 00:23:00,840 OF THOSE PATIENTS, 21%, HAVING A 590 00:23:00,840 --> 00:23:01,280 COMPLETE RESPONSE. 591 00:23:01,280 --> 00:23:02,720 SO VERY, VERY IMPRESSIVE. 592 00:23:02,720 --> 00:23:04,440 THE RESPONSE IN PROSTATE CANCER 593 00:23:04,440 --> 00:23:06,320 WAS NOT AS HIGH, BUT IT WAS A 594 00:23:06,320 --> 00:23:09,640 SMALL COHORT, AND WE ALSO SAW 595 00:23:09,640 --> 00:23:11,120 RESPONSES IN RARE TUMORS, WHICH 596 00:23:11,120 --> 00:23:12,120 IS REALLY IMPORTANT BECAUSE 597 00:23:12,120 --> 00:23:14,840 THERE'S NO STANDARD OF CARE FOR 598 00:23:14,840 --> 00:23:16,240 PATIENTS WITH RARE G.U. TUMORS, 599 00:23:16,240 --> 00:23:19,400 AND THIS INCLUDED PATIENTS WITH 600 00:23:19,400 --> 00:23:21,040 ADENOCARCINOMA, URECHAL, 601 00:23:21,040 --> 00:23:23,440 PATIENTS WITH SQUAMOUS CELL 602 00:23:23,440 --> 00:23:24,640 CARCINOMA OF THE BLADDER, 603 00:23:24,640 --> 00:23:26,040 PATIENTS WITH SPLAWL CELL 604 00:23:26,040 --> 00:23:27,640 CARCINOMA OF THE BLADDER, 605 00:23:27,640 --> 00:23:29,120 PATIENTS WITH PENILE CANCER, WE 606 00:23:29,120 --> 00:23:31,000 SAW SOME VERY NICE RESPONSES. 607 00:23:31,000 --> 00:23:32,640 AND WE ALSO TREATED PATIENTS 608 00:23:32,640 --> 00:23:34,800 WITH GERM CELL BUT DIDN'T SEE 609 00:23:34,800 --> 00:23:36,760 MUCH RESPONSE IN GERM CELL 610 00:23:36,760 --> 00:23:37,160 TUMORS. 611 00:23:37,160 --> 00:23:38,280 HERE'S A PICTURE OF A PATIENT 612 00:23:38,280 --> 00:23:39,040 WITH PENILE CANCER. 613 00:23:39,040 --> 00:23:42,120 HE HAD A FUNGATING MASS AT THE 614 00:23:42,120 --> 00:23:43,520 BEGINNING, AND THEN AFTER FOUR 615 00:23:43,520 --> 00:23:47,240 CYCLES OF TREATMENT, THAT MASS 616 00:23:47,240 --> 00:23:48,320 REGRESSED WITH A VERY NICE 617 00:23:48,320 --> 00:23:55,800 RESPONSE TO THE DOUBLELET -- TO 618 00:23:55,800 --> 00:23:59,240 THE TRIPLET. 619 00:23:59,240 --> 00:24:00,800 WE ALSO HAD SMALL NUMBERS BUT WE 620 00:24:00,800 --> 00:24:05,480 LOOKED AT ALSO PATIENTS WITH 621 00:24:05,480 --> 00:24:07,120 RENO MEDULLARY CARCINOMA AND DID 622 00:24:07,120 --> 00:24:08,120 SEE SOME RESPONSES. 623 00:24:08,120 --> 00:24:11,280 AND BASED ON THIS DATA, I 624 00:24:11,280 --> 00:24:14,240 INITIATED THE ICONIC SPH STUDY, A 625 00:24:14,240 --> 00:24:15,800 COOPERATIVE GROUP STUDY, A LARGE 626 00:24:15,800 --> 00:24:16,840 NATIONAL TRIAL THROUGH THE 627 00:24:16,840 --> 00:24:18,400 COOPERATIVE GROUPS FOR RARE 628 00:24:18,400 --> 00:24:19,680 TUMORS, AND THIS STUDY IS 629 00:24:19,680 --> 00:24:23,920 ONGOING RIGHT NOW, AND IT HAS 630 00:24:23,920 --> 00:24:25,440 MULTIPLE DIFFERENT COHORTS. 631 00:24:25,440 --> 00:24:26,920 IT HAS SQUAMOUS CELL CARCINOMA 632 00:24:26,920 --> 00:24:28,840 OF THE BLADDER, SMALL CELL 633 00:24:28,840 --> 00:24:30,480 CARCINOMA OF THE BLADDER, 634 00:24:30,480 --> 00:24:38,440 ADENOCARCARCINOMA, KIDNEY CANCER 635 00:24:38,440 --> 00:24:40,320 SUBSETS, COLLECTING DUCT RENAL 636 00:24:40,320 --> 00:24:42,840 CELL CARCINOMA, RENAL MEDULLARY 637 00:24:42,840 --> 00:24:46,400 AND OF COURSE I HAVE A GROUP FOR 638 00:24:46,400 --> 00:24:47,200 MISCELLANEOUS TUMORS, FOR THE 639 00:24:47,200 --> 00:24:49,600 RARE, RARE, RARE TUMORS AND ALSO 640 00:24:49,600 --> 00:24:50,240 BONE-ONLY DISEASE, BECAUSE 641 00:24:50,240 --> 00:24:52,040 AGAIN, BONE-ONLY DISEASE IS NOT 642 00:24:52,040 --> 00:24:56,240 ELIGIBLE FOR A TRIAL THAT US A USES 643 00:24:56,240 --> 00:24:59,840 OVERALL RESPONSE RATE. 644 00:24:59,840 --> 00:25:01,840 SO I WANTED TO TALK ABOUT THE 645 00:25:01,840 --> 00:25:04,040 CHECKMATE 90R STUDY BECAUSE I 646 00:25:04,040 --> 00:25:06,960 WAS INVOLVED IN THE DEVELOPMENT 647 00:25:06,960 --> 00:25:09,560 OF THIS PHASE 3 TRIAL AGAIN BASE 648 00:25:09,560 --> 00:25:14,640 OND OUON OUR PHASE 1 DATA THAT WE SAW 649 00:25:14,640 --> 00:25:17,640 WITH THE DOUBLE CABOZANTINIB AND 650 00:25:17,640 --> 00:25:23,200 NIVOLUMAB, SO THIS TRIAL 651 00:25:23,200 --> 00:25:26,880 ENROLLED PATIENTS RANDOMIZED TO 652 00:25:26,880 --> 00:25:31,400 NIVOLUMAB OR CABOZANTINIB 653 00:25:31,400 --> 00:25:32,480 VERSUS -- FOR PATIENTS WITH 654 00:25:32,480 --> 00:25:33,480 METASTATIC KIDNEY CANCER. 655 00:25:33,480 --> 00:25:41,040 THE OUTCOMES OF THIS STUDY WERE 656 00:25:41,040 --> 00:25:45,720 PRESENTED AS ESMOL 2020 AND IT 657 00:25:45,720 --> 00:25:47,200 DOUBLED THE PROGRESSION-FREE 658 00:25:47,200 --> 00:25:48,560 SURVIVAL FOR THE PATIENTS WITH A 659 00:25:48,560 --> 00:25:51,600 HAZARD RATIO OF .51, SO 660 00:25:51,600 --> 00:25:54,000 EXCELLENT RESULTS, IT ALSO 661 00:25:54,000 --> 00:25:55,920 IMPROVED OVERALL SURVIVAL IN 662 00:25:55,920 --> 00:25:57,720 PATIENTS RECEIVING THE DOUBLET 663 00:25:57,720 --> 00:26:00,240 WITH A HAZARD RATIO OF .6, AND 664 00:26:00,240 --> 00:26:02,440 THE OVERALL RESPONSE RATE FOR 665 00:26:02,440 --> 00:26:05,640 KIDNEY CANCER PATIENTS WAS 56%. 666 00:26:05,640 --> 00:26:08,880 SO VERY EXCITING RESULTS VERSUS 667 00:26:08,880 --> 00:26:15,800 27% SEEN WITH STANDARD -- SO THE 668 00:26:15,800 --> 00:26:17,200 FDA GRANTED APPROVAL FOR THE 669 00:26:17,200 --> 00:26:19,080 COMBINATION OF CABOZANTINIB AND 670 00:26:19,080 --> 00:26:20,160 NIVOLUMAB FOR THE FIRST LINE 671 00:26:20,160 --> 00:26:23,040 TREATMENT OF PATIENTS WITH 672 00:26:23,040 --> 00:26:24,160 METASTATIC RENAL CELL CARCINOMA. 673 00:26:24,160 --> 00:26:26,880 I WANTED TO MENTION THE COSMIC 674 00:26:26,880 --> 00:26:27,520 313 STUDY THAT WAS JUST 675 00:26:27,520 --> 00:26:33,720 PRESENTED A MONTH AGO AT ESMO IN 676 00:26:33,720 --> 00:26:37,040 PARIS AT THE ANNUAL MEETING AS A 677 00:26:37,040 --> 00:26:41,080 PLENARY SESSION, SO THIS IS THE 678 00:26:41,080 --> 00:26:42,840 TRIPLE COMBINATION OF 679 00:26:42,840 --> 00:26:46,000 CABOZANTINIB, NIVOLUMAB, AND 680 00:26:46,000 --> 00:26:47,520 IPIMIBULAB, AGAIN BASED ON OUR 681 00:26:47,520 --> 00:26:48,960 PHASE ONE DATA THAT WAS COMPARED 682 00:26:48,960 --> 00:26:50,360 TO -- THIS HAD A DIFFERENT 683 00:26:50,360 --> 00:26:53,440 COMPARATOR, IT WAS COMPARED TO 684 00:26:53,440 --> 00:26:59,440 IMMUNOTHERAPY NIVOLUMAB AND -- 685 00:26:59,440 --> 00:27:01,960 IT WAS A PLACEBO CONTROLLED 686 00:27:01,960 --> 00:27:03,920 STUDY FOR THE CABOZANTINIB AND 687 00:27:03,920 --> 00:27:06,240 THE OUTCOMES SHOWED THIS IS THE 688 00:27:06,240 --> 00:27:08,400 PRELIMINARY OUTCOMES OF THE 689 00:27:08,400 --> 00:27:09,160 PROGRESSION-FREE SURVIVAL SHOW 690 00:27:09,160 --> 00:27:10,800 THAT THE TRIPLE THERAPY HAD A 691 00:27:10,800 --> 00:27:14,840 BENEFIT TO IMMUNOTHERAPY BY 692 00:27:14,840 --> 00:27:15,280 ITSELF. 693 00:27:15,280 --> 00:27:16,480 SO THESE ARE VERY EXCITING 694 00:27:16,480 --> 00:27:17,120 RESULTS. 695 00:27:17,120 --> 00:27:21,200 ALSO BASED ON OUR PHASE ONE 696 00:27:21,200 --> 00:27:24,080 DATA, MANY OTHER STUDIES HAVE 697 00:27:24,080 --> 00:27:25,640 STEMMED OUT, INCLUDING THE 698 00:27:25,640 --> 00:27:27,040 PEDIGREE STUDY, WHICH IS A STUDY 699 00:27:27,040 --> 00:27:28,280 INSTEAD OF ASKING THE QUESTION 700 00:27:28,280 --> 00:27:29,640 OF THE COMBINATION, WHAT ABOUT 701 00:27:29,640 --> 00:27:31,840 THE SEQUENCE, WHAT IF WE GIVE 702 00:27:31,840 --> 00:27:33,240 THE IMMUNOTHERAPY FIRST AND IF 703 00:27:33,240 --> 00:27:35,000 YOU RESPOND, YOU STAY ON THE 704 00:27:35,000 --> 00:27:35,800 IMMUNOTHERAPY BUT IF YOU DON'T 705 00:27:35,800 --> 00:27:39,480 RESPOND U ADD THE CABOZANTINIB 706 00:27:39,480 --> 00:27:43,320 AND ADD CABONIVO, SEQUENTIAL 707 00:27:43,320 --> 00:27:44,280 THERAPY, THIS IS THROUGH THE 708 00:27:44,280 --> 00:27:45,400 ALLIANCE COOPERATIVE GROUP. 709 00:27:45,400 --> 00:27:47,320 AND THEN MANY PHASE TWO STUDIES 710 00:27:47,320 --> 00:27:49,560 IN OTHER TUMORS SUCH AT BREAST 711 00:27:49,560 --> 00:27:53,040 CANCER, CARCINOID HEPATOCELLULAR 712 00:27:53,040 --> 00:27:54,440 CARCINOMA, ENDOMETRIAL AND 713 00:27:54,440 --> 00:27:57,960 UTERINE CANCER. 714 00:27:57,960 --> 00:27:59,200 SO I WANTED TO NEXT TALK ABOUT 715 00:27:59,200 --> 00:28:01,560 MY RESEARCH AIM TWO, WHICH 716 00:28:01,560 --> 00:28:03,240 HIGHLIGHTS SOME OF THE BIOMARKER 717 00:28:03,240 --> 00:28:06,360 WORK THAT I DID WITHIN THESE 718 00:28:06,360 --> 00:28:07,000 TRIALS OF MONOTHERAPY 719 00:28:07,000 --> 00:28:09,080 CABOZANTINIB AND MONOTHERAPY -- 720 00:28:09,080 --> 00:28:10,640 AND COMBINATION CABOZANTINIB 721 00:28:10,640 --> 00:28:12,840 PLUS NIVOLUMAB WITH OR WITHOUT 722 00:28:12,840 --> 00:28:14,360 IPIMIBULAB, AND WE CAN START OUT 723 00:28:14,360 --> 00:28:16,040 WITH CABOZANTINIB MODEL THERAPY, 724 00:28:16,040 --> 00:28:18,920 AND YOU KNOW, I PRE VAST THIS BY 725 00:28:18,920 --> 00:28:20,080 SAYING I KNOW CABOZANTINIB HAS A 726 00:28:20,080 --> 00:28:21,200 LOT OF DIFFERENT TARGETS. 727 00:28:21,200 --> 00:28:24,360 I MEAN, THIS IS THE KINOME OF 728 00:28:24,360 --> 00:28:27,000 CABOZANTINIB AND THE IC50 VALUES 729 00:28:27,000 --> 00:28:28,280 ON THE RIGHT, AND YOU CAN SEE 730 00:28:28,280 --> 00:28:31,440 THAT THERE ARE MULTIPLE RECEPTOR 731 00:28:31,440 --> 00:28:34,200 KINASES THAT ARE TARGETED BY 732 00:28:34,200 --> 00:28:34,520 CABOZANTINIB. 733 00:28:34,520 --> 00:28:36,080 BUT YOU KNOW, WE WERE TRYING TO 734 00:28:36,080 --> 00:28:38,080 FIGURE OUT WHICH IS THE MOST 735 00:28:38,080 --> 00:28:38,360 IMPORTANT. 736 00:28:38,360 --> 00:28:40,520 IS IT THE VEGF PATHWAY, IS IT 737 00:28:40,520 --> 00:28:43,960 THE MET PATHWAY, SO WE STAINED 738 00:28:43,960 --> 00:28:45,040 TUMORS IN PATIENTS THAT ENROLLED 739 00:28:45,040 --> 00:28:48,640 IN OUR CABOZANTINIB STUDY FOR 740 00:28:48,640 --> 00:28:50,160 MET THROUGH 741 00:28:50,160 --> 00:28:50,640 IMMUNOHISTOCHEMISTRY. 742 00:28:50,640 --> 00:28:51,920 THIS WAS A TREMENDOUS EFFORT. 743 00:28:51,920 --> 00:28:55,040 WE HAD 67 SPECIMENS AND 46 744 00:28:55,040 --> 00:28:56,360 PATIENTS WITH BLADDER CANCER, 745 00:28:56,360 --> 00:28:58,520 WITH SMALL CELL BLADDER CANCER, 746 00:28:58,520 --> 00:29:00,440 SQUAMOUS CELL CANCER OF THE 747 00:29:00,440 --> 00:29:01,600 BLADDER, SARCOMATOID AND 748 00:29:01,600 --> 00:29:02,560 ADENOCARCINOMA, AND WE LOOKED AT 749 00:29:02,560 --> 00:29:04,240 THE STAINING BOTH IN THE PRIMARY 750 00:29:04,240 --> 00:29:06,320 TUMOR AND IN THE METASTASES, AND 751 00:29:06,320 --> 00:29:09,240 THIS WAS A TREMENDOUS EFFORT RUN 752 00:29:09,240 --> 00:29:12,760 BY DR. MARIA MARIE KNOW AND 753 00:29:12,760 --> 00:29:19,840 DR. MARK RAFELT AND 754 00:29:19,840 --> 00:29:22,480 UNFORTUNATELY WE DID NOT FIND A 755 00:29:22,480 --> 00:29:24,880 CORRELATION WITH THE IHC 756 00:29:24,880 --> 00:29:26,600 STAINING AND THE OUTCOMES OF HOW 757 00:29:26,600 --> 00:29:27,960 THE PATIENT DID. 758 00:29:27,960 --> 00:29:30,240 ACTUALLY THERE WAS ACTUALLY 759 00:29:30,240 --> 00:29:31,040 INTRAPATIENT HETEROGENEITY, SO 760 00:29:31,040 --> 00:29:33,280 IF I HAD TWO OR THREE SPECIMENS 761 00:29:33,280 --> 00:29:34,400 FROM THE SAME PATIENT IN 762 00:29:34,400 --> 00:29:35,920 DIFFERENT SITES, YOU CAN HAVE 763 00:29:35,920 --> 00:29:37,880 DIFFERENT STAINING OF THE MET 764 00:29:37,880 --> 00:29:38,360 PATHWAY. 765 00:29:38,360 --> 00:29:43,160 SO IT JUST SHOWS THAT THE MET MET 766 00:29:43,160 --> 00:29:44,440 PROTEIN EXPRESSION IS VERY 767 00:29:44,440 --> 00:29:45,560 HETEROGENEOUS AND THERE'S MORE 768 00:29:45,560 --> 00:29:46,840 TO IN TERMS OF THE ACTIVITY OF 769 00:29:46,840 --> 00:29:47,520 CABOZANTINIB. 770 00:29:47,520 --> 00:29:49,480 BUT YOU KNOW, WE LOOKED AT 771 00:29:49,480 --> 00:29:52,560 MULTIPLE DIFFERENT MARKERS, WE 772 00:29:52,560 --> 00:29:54,360 LOOKED AT OTHER TUMOR MARKERS, 773 00:29:54,360 --> 00:29:58,640 WE LOOKED AT SEQUENCING, WE 774 00:29:58,640 --> 00:30:01,520 LOOKED AT MET AND HGF IN PLASMA, 775 00:30:01,520 --> 00:30:04,120 WE LOOKED AT MET AND HGF IN 776 00:30:04,120 --> 00:30:04,800 URINE. 777 00:30:04,800 --> 00:30:07,400 WE LOOKED AT CTCs, WE LOOKED 778 00:30:07,400 --> 00:30:09,360 AT A LOT OF DIFFERENT BIOMARKERS 779 00:30:09,360 --> 00:30:11,120 IN TERMS OF TRYING TO FIND A 780 00:30:11,120 --> 00:30:15,400 CORRELATION AND WE DID NOT FIND 781 00:30:15,400 --> 00:30:16,440 CORRELATION WITH OUTCOMES WITHIN 782 00:30:16,440 --> 00:30:17,560 THESE BIOMARKERS. 783 00:30:17,560 --> 00:30:20,560 BUT WE LOOKED, AND I THINK IT'S 784 00:30:20,560 --> 00:30:21,560 IMPORTANT THAT WE REPORTED THIS 785 00:30:21,560 --> 00:30:24,280 AND WE PUBLISHED THIS. 786 00:30:24,280 --> 00:30:26,040 WE DID FIND PATIENTS WITH HIGH 787 00:30:26,040 --> 00:30:29,000 LEVELS OF PLASMA IL-6 HAD WORSE 788 00:30:29,000 --> 00:30:30,440 PROGRESSION-FREE AND OVERALL 789 00:30:30,440 --> 00:30:33,040 SURVIVAL AND WE KNOW IL-6 IS PRO 790 00:30:33,040 --> 00:30:34,640 INFLAMMATORY CYTOKINE THAT CAN 791 00:30:34,640 --> 00:30:36,320 DIRECTLY STIMULATE TUMOR GROWTH 792 00:30:36,320 --> 00:30:38,560 AND METASTASES AND TARGETING 793 00:30:38,560 --> 00:30:39,920 IL-6 HAS BEEN LIMITED RIGHT NOW 794 00:30:39,920 --> 00:30:41,800 TO REUM TOE LOGIC DISORDERS AND 795 00:30:41,800 --> 00:30:43,840 OTHER CONDITIONS SUCH AS COVID. 796 00:30:43,840 --> 00:30:48,240 SO MOVING ON TO BIOMARKERS, 797 00:30:48,240 --> 00:30:51,840 CABOZANTINIB AND NIVOLUMAB, AND 798 00:30:51,840 --> 00:30:54,320 BIOMARKERS IN THE DOUBLE AND THE 799 00:30:54,320 --> 00:30:54,840 TRIP LET. 800 00:30:54,840 --> 00:30:57,960 I WANTED TO HIGHLIGHT ONE 801 00:30:57,960 --> 00:30:59,600 BIOMARKER LOOKING AT THE CTC 802 00:30:59,600 --> 00:31:06,360 BURDEN IN PATIENTS TREATED WITH 803 00:31:06,360 --> 00:31:12,160 CABONIVO AND CABO NIVOIPI. 804 00:31:12,160 --> 00:31:14,600 SHE'S A UROLOGIST, SHE WAS A 805 00:31:14,600 --> 00:31:16,000 FELLOW WITH THE UROLOGIC 806 00:31:16,000 --> 00:31:17,440 ONCOLOGY BRANCH THAT WORKED WITH 807 00:31:17,440 --> 00:31:20,640 ME AND REALLY HAD A LOT OF -- A 808 00:31:20,640 --> 00:31:22,040 STRONG INTEREST IN LIQUID 809 00:31:22,040 --> 00:31:23,160 BIOPSIES FOR PATIENTS WITH 810 00:31:23,160 --> 00:31:26,120 BLADDER CANCER, AND WE USED THE 811 00:31:26,120 --> 00:31:28,280 IP EMPLATFORM AND WE FOUND 812 00:31:28,280 --> 00:31:32,120 CTCs PRESENT IN 75% OF OUR 813 00:31:32,120 --> 00:31:34,840 CASES, AND THE CTC BURDEN WAS 814 00:31:34,840 --> 00:31:36,400 ASSESSED AT THREE DIFFERENT TIME 815 00:31:36,400 --> 00:31:39,440 POINTS AT BASELINE, CYCLE TWO, 816 00:31:39,440 --> 00:31:40,640 CYCLE THREE, AND WE SAW A 817 00:31:40,640 --> 00:31:43,560 DECLINE OF THE CTCs WITH 818 00:31:43,560 --> 00:31:44,920 THERAPY. 819 00:31:44,920 --> 00:31:46,440 SO AS WE WOULD HOPE TO SEE, AND 820 00:31:46,440 --> 00:31:48,440 THAT THE CTC BURDEN AT BASELINE, 821 00:31:48,440 --> 00:31:53,040 WE USE FOUR CTCs, MORE THAN 822 00:31:53,040 --> 00:31:56,280 FOUR OR LESS THAN FOUR IF THE 823 00:31:56,280 --> 00:31:57,480 PATIENTS HAD MORE THAN FOUR, 824 00:31:57,480 --> 00:31:59,120 THOSE PATIENTS WERE ASSOCIATED 825 00:31:59,120 --> 00:32:01,560 WITH WORSE OUT COME IN TERMS OF 826 00:32:01,560 --> 00:32:03,200 PFS AND OS. 827 00:32:03,200 --> 00:32:06,240 AND WE ACTUALLY ALSO LOOKED AT 828 00:32:06,240 --> 00:32:10,640 THE CTCs THAT WERE 829 00:32:10,640 --> 00:32:11,240 PDL1 POSITIVE, ALSO ASSOCIATED 830 00:32:11,240 --> 00:32:12,560 WITH A POORER PROGNOSIS. 831 00:32:12,560 --> 00:32:14,320 AND THIS IS WHAT WE SEE ALSO IN 832 00:32:14,320 --> 00:32:16,440 TUMORS. 833 00:32:16,440 --> 00:32:20,120 AND YOU KNOW, USING THE EPIC 834 00:32:20,120 --> 00:32:22,640 PLATFORM, WE LOOKED AT 835 00:32:22,640 --> 00:32:25,240 IMMUNOFLUORESCENT MICROSCOPY AND 836 00:32:25,240 --> 00:32:26,560 COMPUTER VISION ALGORITHMS TO 837 00:32:26,560 --> 00:32:29,640 ASSESS THE MORPHOLOGY. 838 00:32:29,640 --> 00:32:31,360 WHAT DOES THE CDC ACTUALLY LOOK 839 00:32:31,360 --> 00:32:31,600 LIKE? 840 00:32:31,600 --> 00:32:39,920 WE LOOKED AT IT IN TERMS OF THE 841 00:32:39,920 --> 00:32:41,680 NUCLEUS -- WAS THE CELL 842 00:32:41,680 --> 00:32:43,280 ELONGATED, AND WE IDENTIFIED 843 00:32:43,280 --> 00:32:48,080 FIVE MORPHOLOGIC SUBTYPES WITHIN 844 00:32:48,080 --> 00:32:50,480 OUR CTCs, WE CATEGORIZED THEM 845 00:32:50,480 --> 00:32:55,840 A, B, C, D AND E, AND WE FOUND 846 00:32:55,840 --> 00:32:57,480 THAT WITHIN SUBTYPE B AND D, 847 00:32:57,480 --> 00:32:59,680 THESE PATIENTS THAT HAD THESE 848 00:32:59,680 --> 00:33:01,760 CTCs, EVEN HAVING ONE OF THESE 849 00:33:01,760 --> 00:33:02,640 CTCs, THESE PATIENTS DID 850 00:33:02,640 --> 00:33:04,040 WORSE. 851 00:33:04,040 --> 00:33:07,880 AT BASELINE AND AT CYCLE 2. 852 00:33:07,880 --> 00:33:11,680 NOW WE'RE ALSO TESTING THIS IN 853 00:33:11,680 --> 00:33:13,040 PATIENTS THAT HAVE MUSCLE 854 00:33:13,040 --> 00:33:14,120 INVASIVE BLADDER CANCER AND 855 00:33:14,120 --> 00:33:16,520 WHETHER THEY HAVE ANY CTCs AND 856 00:33:16,520 --> 00:33:21,280 HOW THE MORPHOLOGIES ARE 857 00:33:21,280 --> 00:33:23,040 DETECTED, HOW DOES THAT 858 00:33:23,040 --> 00:33:24,840 CORRELATE WITH OUTCOME. 859 00:33:24,840 --> 00:33:30,720 SO WE APPLIED THIS EPIC SIGH INS SCIENCE 860 00:33:30,720 --> 00:33:32,400 DETECTION PLATFORM TO ALSO 861 00:33:32,400 --> 00:33:33,560 QUANTIFYING T-CELL POPULATIONS 862 00:33:33,560 --> 00:33:35,120 AND FOUND THAT PATIENTS WITH LOW 863 00:33:35,120 --> 00:33:36,760 BASELINE CD4 T-CELL POPULATIONS 864 00:33:36,760 --> 00:33:39,920 HAD A WORSE PFS AND A WORSE 865 00:33:39,920 --> 00:33:40,720 OVERALL SURVIVAL. 866 00:33:40,720 --> 00:33:43,440 AND WE ALSO FOUND THAT PATIENTS 867 00:33:43,440 --> 00:33:45,840 WITH LOW CD8 T-CELL POPULATIONS 868 00:33:45,840 --> 00:33:48,120 ALSO HAD WORSE PFS AND WORSE 869 00:33:48,120 --> 00:33:49,240 OVERALL SURVIVAL. 870 00:33:49,240 --> 00:33:51,760 AND THEN WE LOOKED AT THE 871 00:33:51,760 --> 00:33:53,600 CD4 AND THE CD8 BASED ON THE 872 00:33:53,600 --> 00:33:55,680 RESPONSE RATE, SO YOU CAN SEE 873 00:33:55,680 --> 00:33:58,520 THE LEFT IS COMPLETE RESPONSE, 874 00:33:58,520 --> 00:33:59,800 PRESSURE RESPONSE, STABLE 875 00:33:59,800 --> 00:34:01,360 DISEASE AND PROGRESSIVE DISEASE, 876 00:34:01,360 --> 00:34:03,640 AND THE PATIENT THAT HAD THE 877 00:34:03,640 --> 00:34:06,640 HIGHER CD4 AND CD8 LEVELS HAD 878 00:34:06,640 --> 00:34:08,680 HIGHER RATES OF CR AND PR RATE. 879 00:34:08,680 --> 00:34:13,200 SO WE SAW THAT CABOZANTINIB HAS 880 00:34:13,200 --> 00:34:16,880 IMMUNOMODULATORY PROPERTIES OF 881 00:34:16,880 --> 00:34:19,600 BOTH IMMUNOSTIMULATORY CELLS AND 882 00:34:19,600 --> 00:34:20,360 IMMUNOSUPPRESSIVE CELLS BUT WHAT 883 00:34:20,360 --> 00:34:27,560 ABOUT WHEN WE COMBINE CABONIVO 884 00:34:27,560 --> 00:34:31,960 AND -- WE LOOKED AT SUPPRESSOR 885 00:34:31,960 --> 00:34:33,920 CELLS, TREATED, AND WHEN YOU 886 00:34:33,920 --> 00:34:36,560 TREATED THEM WITH THE TRIPLET 887 00:34:36,560 --> 00:34:39,640 AND THE DOUBLET, SUPPRESSOR 888 00:34:39,640 --> 00:34:41,560 CELLS DECREASE AND A LOWER 889 00:34:41,560 --> 00:34:43,800 NUMBER WAS ASSOCIATED WITH 890 00:34:43,800 --> 00:34:47,640 BETTER OUT COME FOR SURVIVAL. 891 00:34:47,640 --> 00:34:48,160 MONOCYTES SIGNIFICANTLY 892 00:34:48,160 --> 00:34:51,320 DECREASED BY TREATMENT OF BOTH 893 00:34:51,320 --> 00:34:55,480 THE TRIPLET AND DOUBLET AND -- 894 00:34:55,480 --> 00:34:57,560 HIGHLY INCREASED AFTER TREATMENT 895 00:34:57,560 --> 00:35:02,440 IN CYCLE 2 AND CYCLE 3 WITH THE 896 00:35:02,440 --> 00:35:04,880 TRIPLET BUT ONLILY MILDLY 897 00:35:04,880 --> 00:35:08,040 INCREASED WITH THE DOUBLET. 898 00:35:08,040 --> 00:35:09,440 -- CORRELATED WITH SURVIVAL IN 899 00:35:09,440 --> 00:35:12,640 THE DOUBLET BUT NOT IN THE 900 00:35:12,640 --> 00:35:12,880 TRIPLET. 901 00:35:12,880 --> 00:35:19,280 SO WE HAVE SOME HYPOTHESES ABOUT 902 00:35:19,280 --> 00:35:21,160 THIS, PATIENTS TREATED WITH THE 903 00:35:21,160 --> 00:35:23,440 DOUBLET VERSUS THE TRIPLET MAY 904 00:35:23,440 --> 00:35:27,520 BE ADAPTING RESISTANCE TO 905 00:35:27,520 --> 00:35:28,360 PROLONGED -- WE'RE ACTUALLY 906 00:35:28,360 --> 00:35:30,200 DOING ADDITIONAL STUDIES TOO IN 907 00:35:30,200 --> 00:35:33,160 TUMOR, USING MULTIPLEX IHC 908 00:35:33,160 --> 00:35:34,560 ANALYSIS TO ASSESS THE QUANTITY 909 00:35:34,560 --> 00:35:36,320 AND LOCATION OF THE IMMUNE 910 00:35:36,320 --> 00:35:40,840 SUBSETS WITHIN THESE TUMORS. 911 00:35:40,840 --> 00:35:43,320 SO ALONG WITH TUMOR AND 912 00:35:43,320 --> 00:35:44,520 PERIPHERAL BLOOD BIOMARKERS, I 913 00:35:44,520 --> 00:35:46,440 ALSO INCLUDE SEVERAL IMAGING 914 00:35:46,440 --> 00:35:47,920 AIMS IN THE PHASE ONE STUDY, AND 915 00:35:47,920 --> 00:35:50,560 WE CURRENTLY HAVE A DATABASE OF 916 00:35:50,560 --> 00:35:52,120 OVER 400 PET SCANS DONE WITHIN 917 00:35:52,120 --> 00:35:56,680 THESE STUDIES, BOTH FDG AND 918 00:35:56,680 --> 00:35:58,240 SODIUM FLUORIDE OR COMBINED, AND 919 00:35:58,240 --> 00:35:59,640 WE'RE ANALYZING THESE IN 920 00:35:59,640 --> 00:36:02,040 COLLABORATION WITH 921 00:36:02,040 --> 00:36:03,880 DR. LINDENBERG AND DR. AMENA NAT 922 00:36:03,880 --> 00:36:05,880 ONLY WITH THE OUTCOMES BUT ALSO 923 00:36:05,880 --> 00:36:11,920 WITH BIOMARKERS SUCH AS CTCs 924 00:36:11,920 --> 00:36:14,000 AND CTBNA. 925 00:36:14,000 --> 00:36:15,080 IT'S A VERY IMPORTANT STUDY, 926 00:36:15,080 --> 00:36:17,120 THIS IS THE PHASE III TRIAL THAT 927 00:36:17,120 --> 00:36:19,080 I RUN THROUGH THE COOPERATIVE 928 00:36:19,080 --> 00:36:21,960 GROUP AND IT HAS COMPLETED 929 00:36:21,960 --> 00:36:25,560 ACCRUAL OF 700 PATIENTS, AND 930 00:36:25,560 --> 00:36:27,720 THIS IS FOR PATIENTS THAT HAVE 931 00:36:27,720 --> 00:36:29,640 MUSCLE INVASIVE BLADDER CANCER. 932 00:36:29,640 --> 00:36:32,680 THEY'RE RANDOMIZED TO RECEIVE 933 00:36:32,680 --> 00:36:34,760 PEMBROLIZUMAB VERSUS 934 00:36:34,760 --> 00:36:36,080 OBSERVATION, AND WITH THE 935 00:36:36,080 --> 00:36:38,400 PRIMARY OUTCOME OF OVERALL 936 00:36:38,400 --> 00:36:40,360 SURVIVAL AND DISEASE-FREE 937 00:36:40,360 --> 00:36:40,960 SURVIVAL. 938 00:36:40,960 --> 00:36:44,720 SO WITH THIS TRIAL COMES A LOT 939 00:36:44,720 --> 00:36:46,320 OF CORRELATIVES AND THAT'S ONE 940 00:36:46,320 --> 00:36:49,880 OF THE WONDERFUL THINGS ABOUT 941 00:36:49,880 --> 00:36:52,040 DOING THESE LARGE PHASE 942 00:36:52,040 --> 00:36:53,480 3 TRIALS, IS THE OPPORTUNITIES 943 00:36:53,480 --> 00:36:57,360 TO COLLABORATE WITH MULTIPLE 944 00:36:57,360 --> 00:36:59,480 NATIONAL INVESTIGATORS AT 945 00:36:59,480 --> 00:37:00,320 MULTIPLE DIFFERENT INSTITUTES 946 00:37:00,320 --> 00:37:04,840 AND WITHIN THE NCI, SO WE'RE 947 00:37:04,840 --> 00:37:07,240 DOING IMMUNE GENE SIGNATURE, RNA 948 00:37:07,240 --> 00:37:11,000 SUBTYPING, TUMOR TCR CLONALITY, 949 00:37:11,000 --> 00:37:15,920 IMMUNE PROFILING PBMCs, 950 00:37:15,920 --> 00:37:16,480 IMMUNOMODULATORY CYTOKINES, 951 00:37:16,480 --> 00:37:19,160 DIRECT HLA SEQUENCING AND 952 00:37:19,160 --> 00:37:20,040 NEOANTIGEN PREDICTION. 953 00:37:20,040 --> 00:37:23,320 ONE CORRELATIVE I WANTED TO 954 00:37:23,320 --> 00:37:25,640 HIGHLIGHT IS A CT DNA ASSAY 955 00:37:25,640 --> 00:37:28,360 WE'RE ACTUALLY DOING BOTH WITH 956 00:37:28,360 --> 00:37:30,760 NATERRA AND FOUNDATION MEDICINE. 957 00:37:30,760 --> 00:37:33,480 WHY THIS IS IMPORTANT IS 958 00:37:33,480 --> 00:37:36,640 BECAUSE -- SO THE PATIENT 959 00:37:36,640 --> 00:37:38,440 UNDERGOES A RADICAL SURGERY, AND 960 00:37:38,440 --> 00:37:40,400 THEY'RE SUPPOSEDLY NAD, THERE'S 961 00:37:40,400 --> 00:37:42,680 NO CANCER THAT'S DETECTED ON 962 00:37:42,680 --> 00:37:44,560 IMAGING, BUT LIKE I TOLD YOU 963 00:37:44,560 --> 00:37:45,840 EARLIER, ABOUT MORE THAN HALF OF 964 00:37:45,840 --> 00:37:46,960 THOSE PATIENTS WILL HAVE THEIR 965 00:37:46,960 --> 00:37:48,520 CANCER COME BACK, AND IT USUALLY 966 00:37:48,520 --> 00:37:49,920 COMES BACK METASTATIC, SO IT 967 00:37:49,920 --> 00:37:51,560 MEANS THAT THERE'S CIRCULATING 968 00:37:51,560 --> 00:37:53,120 TUMORS GOING ON IN THE BODY THAT 969 00:37:53,120 --> 00:37:54,640 WE JUST CAN'T DETECT, WE JUST 970 00:37:54,640 --> 00:37:56,400 CAN'T SEE ANYTHING ON IMAGING, 971 00:37:56,400 --> 00:37:59,360 BUT THERE'S -- OBVIOUSLY THESE 972 00:37:59,360 --> 00:38:01,520 PATIENTS HAVE ALREADY MICRO 973 00:38:01,520 --> 00:38:03,440 METASTATIC DISEASE, SO THAT'S 974 00:38:03,440 --> 00:38:04,640 WHAT THIS MARKER IS GOING TO 975 00:38:04,640 --> 00:38:05,160 LOOK AT. 976 00:38:05,160 --> 00:38:07,160 AND THIS IS A PERSONALIZED ASSAY 977 00:38:07,160 --> 00:38:09,240 WHERE WE TAKE THE TUMOR, THE 978 00:38:09,240 --> 00:38:11,000 TUMOR TISSUE AND THE GERMLINE 979 00:38:11,000 --> 00:38:11,760 MATERIAL FROM THE PATIENTS AND 980 00:38:11,760 --> 00:38:13,760 WE DO WHOLE EXOME SEQUENCING, 981 00:38:13,760 --> 00:38:16,080 AND LOOK AT THE MUTATIONS, UP TO 982 00:38:16,080 --> 00:38:20,200 16 MUTATIONS ARE SELECTED FOR 983 00:38:20,200 --> 00:38:23,320 PCR, CTDNA ASSAY FOR EACH OF 984 00:38:23,320 --> 00:38:24,760 THESE PATIENTS AND THEN WE TAKE 985 00:38:24,760 --> 00:38:26,080 THE PLASMA SAMPLES, WE SEQUENCE 986 00:38:26,080 --> 00:38:27,600 THAT, AND IF WE FIND AT LEAST 987 00:38:27,600 --> 00:38:28,920 TWO OF THE MUTATIONS THAT WE 988 00:38:28,920 --> 00:38:31,040 FOUND IN THE TUMOR IN THE 989 00:38:31,040 --> 00:38:33,520 PLASMA, THEN WE CONSIDER THOSE 990 00:38:33,520 --> 00:38:34,280 PATIENTS CT DNA POSITIVE. 991 00:38:34,280 --> 00:38:35,720 AND THERE'S A LOT OF DIFFERENT 992 00:38:35,720 --> 00:38:37,680 AIMS THAT WE'RE LOOKING AT WITH 993 00:38:37,680 --> 00:38:39,680 THE CT DNA ASSAY. 994 00:38:39,680 --> 00:38:43,280 NUMBER ONE IS, PROGNOSTICLY. 995 00:38:43,280 --> 00:38:48,080 THE PATIENTS THAT ARE CTDNA 996 00:38:48,080 --> 00:38:49,640 POSITIVE, HOW DO THEY COMPARE TO 997 00:38:49,640 --> 00:38:51,240 PATIENTS THAT ARE CT DNA 998 00:38:51,240 --> 00:38:51,680 NEGATIVE. 999 00:38:51,680 --> 00:38:54,880 ALSO, CAN WE CORRELATE THE CT 1000 00:38:54,880 --> 00:38:56,080 DNA WITH THE RESPONSE WE SEE IN 1001 00:38:56,080 --> 00:38:57,960 THE PATIENTS THAT DO GET 1002 00:38:57,960 --> 00:39:00,080 TREATMENT WITH PEMBROLIZUMAB, 1003 00:39:00,080 --> 00:39:01,880 WITH THE CHECKPOINT INHIBITOR. 1004 00:39:01,880 --> 00:39:04,960 AND ALSO WHAT IS THE LEAD TIME 1005 00:39:04,960 --> 00:39:06,960 OF CT DNA POSITIVITY VERSUS WHAT 1006 00:39:06,960 --> 00:39:08,240 WE SEE ON IMAGING? 1007 00:39:08,240 --> 00:39:09,880 SO THERE'S A LOT OF DIFFERENT 1008 00:39:09,880 --> 00:39:11,320 AIMS, OTHER QUESTIONS THAT WE 1009 00:39:11,320 --> 00:39:13,200 HAVE IS WHEN THE PATIENTS GET 1010 00:39:13,200 --> 00:39:15,680 PEMBROLIZUMAB, DO THEY CLEAR IT. 1011 00:39:15,680 --> 00:39:18,760 DO THEY CLEAR THEIR CT DNA, AND 1012 00:39:18,760 --> 00:39:22,040 WHAT ABOUT IF WE COMBINE CT DNA 1013 00:39:22,040 --> 00:39:25,000 AND TUMOR MUTATION OF BURDEN OR 1014 00:39:25,000 --> 00:39:28,280 PDL1 STATUS AND USE IT AS A 1015 00:39:28,280 --> 00:39:30,800 MULTIMODAL BIOMARKER TO ASSESS 1016 00:39:30,800 --> 00:39:31,800 OUTCOMES IN THESE PATIENTS. 1017 00:39:31,800 --> 00:39:33,560 SO THERE'S A LOT OF QUESTIONS, 1018 00:39:33,560 --> 00:39:35,440 AND I'M VERY EXCITED ABOUT THIS 1019 00:39:35,440 --> 00:39:36,920 CORRELATIVE THAT WE'RE DOING. 1020 00:39:36,920 --> 00:39:41,320 ANOTHER STUDY THAT I WANTED TO 1021 00:39:41,320 --> 00:39:51,680 MENTION IS A STUDY WITH 1022 00:39:51,680 --> 00:39:52,360 AVELUMAB. 1023 00:39:52,360 --> 00:39:55,520 I WAS VERY FORTUNATE TO BE ASKED 1024 00:39:55,520 --> 00:39:57,640 TO RUN THE BLADDER CANCER 1025 00:39:57,640 --> 00:39:59,240 COHORT, AND WE DID THAT AND WE 1026 00:39:59,240 --> 00:40:02,880 SAW SOME VERY NICE RESPONSES, 1027 00:40:02,880 --> 00:40:04,840 18% RESPONSE, AND THESE ARE 1028 00:40:04,840 --> 00:40:06,760 THE -- THIS IS THE PHASE ONE 1029 00:40:06,760 --> 00:40:08,440 STUDY I WAS TELLING YOU ABOUT. 1030 00:40:08,440 --> 00:40:09,680 I WAS RUNNING THE CABOZANTINIB 1031 00:40:09,680 --> 00:40:10,320 AT THE SAME TIME AND I WAS 1032 00:40:10,320 --> 00:40:11,720 RUNNING THIS ONE, AND WE SAW 1033 00:40:11,720 --> 00:40:14,240 SOME VERY NICE RESPONSES IN 1034 00:40:14,240 --> 00:40:16,560 PATIENTS THAT WERE DURABLE. 1035 00:40:16,560 --> 00:40:18,320 SO 18% RESPONSE WITH DURABLE 1036 00:40:18,320 --> 00:40:19,160 RESPONSES. 1037 00:40:19,160 --> 00:40:22,320 AND BASED ON THIS FINDING, WE 1038 00:40:22,320 --> 00:40:24,200 EXPANDED THE BLADDER CANCER 1039 00:40:24,200 --> 00:40:28,440 COHORT TO 250 PATIENTS, AND 1040 00:40:28,440 --> 00:40:29,760 AGAIN CONSISTENTLY SAW 18% 1041 00:40:29,760 --> 00:40:30,920 RESPONSE RATE IN THESE PATIENTS 1042 00:40:30,920 --> 00:40:35,040 AND BASED ON THIS DATA IN 2017, 1043 00:40:35,040 --> 00:40:39,440 THE FDA GRANTED ACCELERATED 1044 00:40:39,440 --> 00:40:42,480 APPROVAL FOR AVELUMAB FOR THE 1045 00:40:42,480 --> 00:40:51,320 SECOND LINE TREATMENT OF 1046 00:40:51,320 --> 00:40:51,600 PATIENTS. 1047 00:40:51,600 --> 00:40:57,680 THIS WAS PRESENTED AT THE 1048 00:40:57,680 --> 00:41:01,560 PLENARY SESSION IN 2020. 1049 00:41:01,560 --> 00:41:02,760 AFTER CHEMOTHERAPY, USUALLY WE 1050 00:41:02,760 --> 00:41:04,640 DO NOTHING, BUT WHAT ABOUT 1051 00:41:04,640 --> 00:41:05,920 GIVING AVELUMAB AT THAT POINT 1052 00:41:05,920 --> 00:41:07,520 VERSUS GIVING NOTHING, AND 700 1053 00:41:07,520 --> 00:41:08,760 PATIENTS WERE RANDOMIZED WITH 1054 00:41:08,760 --> 00:41:11,080 THE PRIMARY OUTCOME OF OVERALL 1055 00:41:11,080 --> 00:41:12,280 SURVIVAL, AND THERE WAS A 1056 00:41:12,280 --> 00:41:13,160 SURVIVAL BENEFIT FOR PATIENTS 1057 00:41:13,160 --> 00:41:15,600 THAT RECEIVED AVELUMAB VERSUS 1058 00:41:15,600 --> 00:41:18,320 THE PATIENTS THAT RECEIVED BEST 1059 00:41:18,320 --> 00:41:19,600 SUPPORTIVE CARE. 1060 00:41:19,600 --> 00:41:21,560 BASED ON THIS DATA, AVELUMAB NOW 1061 00:41:21,560 --> 00:41:24,280 RECEIVED A SECOND APPROVAL IN 1062 00:41:24,280 --> 00:41:25,480 JUNE 2020, SO NOW IT HAS THE 1063 00:41:25,480 --> 00:41:26,920 APPROVAL FOR THE SECOND LINE 1064 00:41:26,920 --> 00:41:28,240 STUDY AND THAT ALSO HAS APPROVAL 1065 00:41:28,240 --> 00:41:29,560 FOR THE MAINTENANCE STUDY. 1066 00:41:29,560 --> 00:41:32,840 SO VERY PROUD OF THE DEVELOPMENT 1067 00:41:32,840 --> 00:41:46,520 AFTER MAN ALSO THROUGDEVELOPMENTAFTERDEVEL OPMENTOF DEVELOPMENT 1068 00:41:46,520 --> 00:41:54,640 OF AVELUMAB. 1069 00:41:54,640 --> 00:41:58,800 THIS STUDY, THIS MOLECULE 1070 00:41:58,800 --> 00:42:01,560 POTENTIALLY CAN OVER -- 1071 00:42:01,560 --> 00:42:03,440 POTENTIALLY CAN OVERCOME 1072 00:42:03,440 --> 00:42:04,360 RESISTANCE IN PATIENTS RESISTANT 1073 00:42:04,360 --> 00:42:06,120 TO CHECKPOINT INHIBITORS. 1074 00:42:06,120 --> 00:42:09,840 WE HAVE A PHASE ONE TRIAL IN 1075 00:42:09,840 --> 00:42:13,360 COMBINATION WITH IL12 AND IN 1076 00:42:13,360 --> 00:42:15,320 COMBINATION WITH RADIATION AT 1077 00:42:15,320 --> 00:42:16,520 MULTIPLE DIFFERENT DOSES, SEEING 1078 00:42:16,520 --> 00:42:17,840 IF WE CAN ENHANCE THE EFFECT 1079 00:42:17,840 --> 00:42:23,920 THAT WE SAW ALREADY WITH 1080 00:42:23,920 --> 00:42:25,040 MONOTHERAPY AVELUMAB WITH THESE 1081 00:42:25,040 --> 00:42:25,840 COMBINATIONS. 1082 00:42:25,840 --> 00:42:27,360 I DON'T HAVE A LOT OF TIME BUT I 1083 00:42:27,360 --> 00:42:31,640 DID WANT TO MENTION MY THIRD 1084 00:42:31,640 --> 00:42:36,760 AIM, WHICH IS TO DEVELOP 1085 00:42:36,760 --> 00:42:37,840 EFFECTIVE THERAPIES FOR PATIENTS 1086 00:42:37,840 --> 00:42:38,760 WITH RARE TUMORS. 1087 00:42:38,760 --> 00:42:43,880 AND WE ALREADY TALKED ABOUT THE 1088 00:42:43,880 --> 00:42:48,000 CABONI. 1089 00:42:48,000 --> 00:42:50,360 NIVO IPI STUDY. 1090 00:42:50,360 --> 00:42:53,840 THIS IS FOR RARE TUMORS. 1091 00:42:53,840 --> 00:42:56,720 THE STUDY HAS ALREADY ACCRUED 1092 00:42:56,720 --> 00:42:57,920 163 PATIENTS, AND WE HAVE SEEN 1093 00:42:57,920 --> 00:42:59,840 SOME VERY NICE ACTIVITY AND ARE 1094 00:42:59,840 --> 00:43:01,240 PLANNING ON EXPANDING THESE 1095 00:43:01,240 --> 00:43:02,440 COHORTS. 1096 00:43:02,440 --> 00:43:04,920 AND BECAUSE WE SEE THESE RARE 1097 00:43:04,920 --> 00:43:06,800 TUMORS AT THE NCI, I HAVE A 1098 00:43:06,800 --> 00:43:09,880 NATURAL HISTORY STUDY THAT I 1099 00:43:09,880 --> 00:43:11,880 OPENED, SO WE CAN BETTER LEARN 1100 00:43:11,880 --> 00:43:13,160 ABOUT THE NATURAL HISTORY OF A 1101 00:43:13,160 --> 00:43:16,880 LOT OF THESE RARE TUMORS FROM 1102 00:43:16,880 --> 00:43:18,320 DIAGNOSIS TO DEFINITIVE THERAPY 1103 00:43:18,320 --> 00:43:21,240 TO SYSTEMIC THERAPY TO DEATH. 1104 00:43:21,240 --> 00:43:24,280 ALL OF THE STAGES IN BETWEEN 1105 00:43:24,280 --> 00:43:28,840 WHERE WE COLLECT TUMOR, PLASMA, 1106 00:43:28,840 --> 00:43:32,520 SALIVA, URINE, AND DO IMAGING TO 1107 00:43:32,520 --> 00:43:36,240 REALLY UNDERSTAND THE NATURAL 1108 00:43:36,240 --> 00:43:41,040 HISTORY OF THESE RARE G.U. 1109 00:43:41,040 --> 00:43:42,160 TUMORS. 1110 00:43:42,160 --> 00:43:43,600 WE HAD AN AUTOPSY PROGRAM HERE 1111 00:43:43,600 --> 00:43:45,760 AT THE NCI. 1112 00:43:45,760 --> 00:43:48,040 WE HAVE A RAPID AUTOPSY PROTOCOL 1113 00:43:48,040 --> 00:43:49,960 WE'RE A PART OF BUT MOST OF OUR 1114 00:43:49,960 --> 00:43:51,440 AUTOPSIES, WE'VE DONE ABOUT 35 1115 00:43:51,440 --> 00:43:53,240 AUTOPSIES ON OUR PATIENTS, MOST 1116 00:43:53,240 --> 00:43:55,640 OF THEM ARE NOT RAPID, AND I 1117 00:43:55,640 --> 00:43:58,800 REALLY WANT TO THANK DR. KLEINER 1118 00:43:58,800 --> 00:44:02,040 AND DR. THAN HUITT FOR REALLY HELPING 1119 00:44:02,040 --> 00:44:07,040 US WITH DOING THESE AUTOPSIES 1120 00:44:07,040 --> 00:44:08,640 AND THE EDUCATIONAL COMPONENT TO 1121 00:44:08,640 --> 00:44:12,640 OUR STUDENTS. 1122 00:44:12,640 --> 00:44:14,040 I WANT TO ALSO HIGHLIGHT TWO 1123 00:44:14,040 --> 00:44:18,640 OTHER STUDIES WITH ANTIBODY 1124 00:44:18,640 --> 00:44:18,920 CONJUGATES. 1125 00:44:18,920 --> 00:44:22,160 ONE IS AN ANTIBODY DRUG 1126 00:44:22,160 --> 00:44:28,040 CONJUGATE THAT TARGETS NECTIN-4. 1127 00:44:28,040 --> 00:44:31,360 THE LINGER RELEASES THE 1128 00:44:31,360 --> 00:44:33,240 CYTOTOXIC AGENT WHEN IT GETS TO 1129 00:44:33,240 --> 00:44:34,960 THE TARGET, HIGHLY EXPRESSED IN 1130 00:44:34,960 --> 00:44:40,760 BLADDER TUMORS AND NOW WE HAVE 1131 00:44:40,760 --> 00:44:43,400 150 SPECIMENS FOR RARE TUMORS 1132 00:44:43,400 --> 00:44:46,480 THAT WE'RE TESTING NECTIN-4 TO 1133 00:44:46,480 --> 00:44:48,800 SEE IF WE CAN POTENTIALLY USE 1134 00:44:48,800 --> 00:44:50,320 FOR THESE RARE TUMORS, AND 1135 00:44:50,320 --> 00:44:51,240 THERE'S ALREADY LITERATURE 1136 00:44:51,240 --> 00:44:53,960 SHOWING THAT NECTIN-4 IS 1137 00:44:53,960 --> 00:44:55,320 EXPRESSED IN SOME OF THESE RARE 1138 00:44:55,320 --> 00:44:56,960 TUMORS SO WE HAVE INITIATED A 1139 00:44:56,960 --> 00:44:59,040 PHASE 2 TRIAL WHERE WE TEST EV 1140 00:44:59,040 --> 00:45:01,920 IN PATIENTS AND THIS IS MY 1141 00:45:01,920 --> 00:45:05,280 FELLOW RIGHT NOW THAT'S HELPING 1142 00:45:05,280 --> 00:45:07,160 ME DEVELOP THIS, WHERE WE TEST 1143 00:45:07,160 --> 00:45:09,040 EV WITH OR WITHOUT IMMUNOTHERAPY 1144 00:45:09,040 --> 00:45:18,120 IN THESE RARE TUMORS. 1145 00:45:18,120 --> 00:45:20,600 ANOTHER ANTIBODY DRUG CONJUGATE 1146 00:45:20,600 --> 00:45:25,760 DIRECTED TOWARD TROP 2 WITH 1147 00:45:25,760 --> 00:45:31,560 SN-38, THE PARENT COMPOUND -- 1148 00:45:31,560 --> 00:45:33,200 WE'VE SEEN ACTIVITY IN BLADDER 1149 00:45:33,200 --> 00:45:34,680 CANCER, SO I'M ALSO GOING TO 1150 00:45:34,680 --> 00:45:40,560 CONDUCT A TRIAL AND THIS WAS DR. KIDD, ONE OF MY FELLOWS 1151 00:45:40,560 --> 00:45:42,240 HELPED ME DEVELOP THIS CLINICAL 1152 00:45:42,240 --> 00:45:49,440 TRIAL TO TEST IN PATIENTS WITH 1153 00:45:49,440 --> 00:45:50,280 RARE TUMORS. 1154 00:45:50,280 --> 00:45:51,480 THIS IS IN DEVELOPMENT. 1155 00:45:51,480 --> 00:45:55,440 WE ALSO HAVE ANOTHER TRIAL IN 1156 00:45:55,440 --> 00:45:59,840 SMALL WEL CELL PATIENTS THAT OUR 1157 00:45:59,840 --> 00:46:01,200 FELLOW NOW ATTENDING DR. SIMON 1158 00:46:01,200 --> 00:46:02,800 HAS HELPED US DEVELOP IN 1159 00:46:02,800 --> 00:46:03,680 PATIENTS WITH SPLAWL CELL 1160 00:46:03,680 --> 00:46:04,440 BLADDER CANCERS. 1161 00:46:04,440 --> 00:46:06,400 THIS STUDY IS ALSO IN 1162 00:46:06,400 --> 00:46:06,680 DEVELOPMENT. 1163 00:46:06,680 --> 00:46:11,000 SO WHEN I JOINED THE NCI ALMOST 1164 00:46:11,000 --> 00:46:12,400 13 YEARS AGO, THERE WAS NO 1165 00:46:12,400 --> 00:46:13,600 BLADDER CANCER PROGRAM AND HI A 1166 00:46:13,600 --> 00:46:15,360 VISION OF INITIATING A 1167 00:46:15,360 --> 00:46:17,960 TRANSLATIONAL BLADDER CANCER 1168 00:46:17,960 --> 00:46:19,480 PROGRAM FOCUSING ON 1169 00:46:19,480 --> 00:46:20,120 SCIENCE-DRIVEN CLINICAL TRIALS 1170 00:46:20,120 --> 00:46:21,600 AT MULTIPLE STAGES OF DISEASE, 1171 00:46:21,600 --> 00:46:23,560 INCLUDING METASTATIC, FIRST 1172 00:46:23,560 --> 00:46:25,640 LINE, SECOND LINE AND BEYOND, 1173 00:46:25,640 --> 00:46:27,640 MUSCLE INVASIVE AND NON-MUSCLE 1174 00:46:27,640 --> 00:46:29,640 INVASIVE, AND WE HAVE CREATED A 1175 00:46:29,640 --> 00:46:31,440 LARGE BLADDER CANCER PROGRAM 1176 00:46:31,440 --> 00:46:33,440 WITH A LOT OF CLINICAL TRIAL 1177 00:46:33,440 --> 00:46:34,880 OPTIONS FOR OUR PATIENTS AT 1178 00:46:34,880 --> 00:46:37,840 MULTIPLE DIFFERENT STAGES. 1179 00:46:37,840 --> 00:46:39,840 SO THE PINK ARE TRIALS THAT HAVE 1180 00:46:39,840 --> 00:46:40,200 BEEN COMPLETED. 1181 00:46:40,200 --> 00:46:41,360 THE GREEN ARE TRIALS THAT ARE 1182 00:46:41,360 --> 00:46:43,560 OPEN AND ACCRUING RIGHT NOW, AND 1183 00:46:43,560 --> 00:46:45,840 THE PURPLE ARE TRIALS JUST ABOUT 1184 00:46:45,840 --> 00:46:47,640 TO OPEN THAT ARE IN DEVELOPMENT. 1185 00:46:47,640 --> 00:46:50,760 AND IT HAS BEEN REALLY THROUGH 1186 00:46:50,760 --> 00:46:53,440 HELP WITH OUR CLINICAL 1187 00:46:53,440 --> 00:46:55,440 COLLABORATORS TO HELP US RUN 1188 00:46:55,440 --> 00:46:57,600 THESE TRIALS IN THE UROLOGIC 1189 00:46:57,600 --> 00:46:59,600 ONCOLOGY BRANCH, WITH OUR 1190 00:46:59,600 --> 00:47:01,560 UROLOGISTS, OUR RADIATION 1191 00:47:01,560 --> 00:47:05,720 ONCOLOGISTS, OUR PATHOLOGISTS, 1192 00:47:05,720 --> 00:47:07,360 AND OUR INTERVENTIONAL 1193 00:47:07,360 --> 00:47:07,640 RADIOLOGIST. 1194 00:47:07,640 --> 00:47:08,680 BUT EVEN DOING THESE TRIALS, IT 1195 00:47:08,680 --> 00:47:10,240 IS REALLY THROUGH COLLABORATION 1196 00:47:10,240 --> 00:47:12,440 WITH OUR SCIENTIFIC 1197 00:47:12,440 --> 00:47:16,440 COLLABORATORS, OUR COLLEAGUES, 1198 00:47:16,440 --> 00:47:19,320 IMMUNOLOGISTS, MICRO BIOLOGISTS, 1199 00:47:19,320 --> 00:47:20,360 GENOMICS AND A PHARMACOLOGIST, 1200 00:47:20,360 --> 00:47:26,440 THAT WE CAN SPA UNDERSTAND THE 1201 00:47:26,440 --> 00:47:27,960 MECHANISMS OF THESE DRUGS, WHY 1202 00:47:27,960 --> 00:47:29,120 THEY WORK IN CERTAIN PATIENTS 1203 00:47:29,120 --> 00:47:30,520 AND NOT IN OTHERS THAT I HAVE 1204 00:47:30,520 --> 00:47:31,840 REALLY BEEN ABLE TO BUILD THIS 1205 00:47:31,840 --> 00:47:32,360 TRANSLATIONAL PROGRAM. 1206 00:47:32,360 --> 00:47:33,720 SO WITH THAT, I THANK YOU SO 1207 00:47:33,720 --> 00:47:36,240 MUCH FOR YOUR ATTENTION, AND I 1208 00:47:36,240 --> 00:47:39,280 WANT TO GIVE A SPECIAL THANK YOU 1209 00:47:39,280 --> 00:47:40,640 TO MY MENTORSHIP COMMITTEE. 1210 00:47:40,640 --> 00:47:42,640 I KNOW I'M TENURED, I BECAME 1211 00:47:42,640 --> 00:47:43,840 TENURED IN NOVEMBER, BUT THEY 1212 00:47:43,840 --> 00:47:46,000 HAVE HELPED ME OVER THE LAST 10 1213 00:47:46,000 --> 00:47:56,320 YEARS GET HERE. 1214 00:47:56,320 --> 00:48:01,640 MY WONDERFUL BLADDER CANCER 1215 00:48:01,640 --> 00:48:03,360 TEAM. 1216 00:48:03,360 --> 00:48:09,400 MILMY WONDERFUL RESEARCH NURSES. 1217 00:48:09,400 --> 00:48:11,360 OUR PATIENT CARE COORDINATOR, 1218 00:48:11,360 --> 00:48:15,640 OUR FANTASTIC PHARMACIST, AND 1219 00:48:15,640 --> 00:48:16,720 OUR VOLUNTEER WHO ALWAYS COMES 1220 00:48:16,720 --> 00:48:17,920 TO CLINIC. 1221 00:48:17,920 --> 00:48:19,720 OUR LAB COLLABORATORS, AND WE 1222 00:48:19,720 --> 00:48:21,760 HAVE A NEW LAB PERSON, A NEW 1223 00:48:21,760 --> 00:48:25,640 STAFF SCIENTIST THAT IS JUST 1224 00:48:25,640 --> 00:48:27,600 JOINING US, ALSO STARTING THE 1225 00:48:27,600 --> 00:48:29,320 GENOMICS STUDIES IN BLADDER 1226 00:48:29,320 --> 00:48:30,760 CANCER, SO VERY EXCITED TO HAVE 1227 00:48:30,760 --> 00:48:34,840 HIM, AND OUR LONG TERM 1228 00:48:34,840 --> 00:48:35,680 COLLABORATIONS, AND THANK YOU SO 1229 00:48:35,680 --> 00:48:37,120 MUCH, EVERYBODY, FOR YOUR 1230 00:48:37,120 --> 00:48:37,440 ATTENTION. 1231 00:48:37,440 --> 00:48:41,400 I REALLY APPRECIATE YOUR TIME. 1232 00:48:41,400 --> 00:48:43,600 >> WELL, THANK YOU SO MUCH FOR 1233 00:48:43,600 --> 00:48:44,400 THAT, ANDREA. 1234 00:48:44,400 --> 00:48:48,280 THAT WAS A TRULY ELEGANT 1235 00:48:48,280 --> 00:48:48,840 PRESENTATION. 1236 00:48:48,840 --> 00:48:49,640 WE CERTAINLY HAVE TIME FOR 1237 00:48:49,640 --> 00:48:50,760 QUESTIONS IF YOU WOULD PLEASE 1238 00:48:50,760 --> 00:48:54,800 SEND IN YOUR QUESTIONS. 1239 00:48:54,800 --> 00:48:56,160 I DO HAVE A COUPLE OF QUESTIONS 1240 00:48:56,160 --> 00:48:57,120 WHILE PEOPLE ARE WAITING TO SEND 1241 00:48:57,120 --> 00:49:00,840 IN THEIRS. 1242 00:49:00,840 --> 00:49:02,240 SO YOU STARTED OFF TALKING ABOUT 1243 00:49:02,240 --> 00:49:03,800 STANDARD OF CARE TREATMENT FOR 1244 00:49:03,800 --> 00:49:05,440 PATIENTS WITH BLADDER CANCER AND 1245 00:49:05,440 --> 00:49:08,920 THE SURGERIES INVOLVED FOR 1246 00:49:08,920 --> 00:49:10,680 MUSCLE INVASIVE BLADDER CANCER 1247 00:49:10,680 --> 00:49:13,360 WITH CYSTECTOMY AND THE 1248 00:49:13,360 --> 00:49:15,520 NEOBLADDER FORMATION AND THE 1249 00:49:15,520 --> 00:49:16,280 SIGNIFICANT MORBIDITY, REALLY, 1250 00:49:16,280 --> 00:49:20,400 THAT THAT DOES AFFORD PATIENTS. 1251 00:49:20,400 --> 00:49:23,800 I'M WONDERING, NOW THAT WE SAW 1252 00:49:23,800 --> 00:49:26,960 IN JUNE THE BEAUTIFUL PAPER, 1253 00:49:26,960 --> 00:49:29,800 JUST 12 PATIENTS EARLY ON WITH 1254 00:49:29,800 --> 00:49:33,640 MSI HIGH RECTAL CANCER SHOWING 1255 00:49:33,640 --> 00:49:35,440 THAT MAYBE WE DON'T NEED TO 1256 00:49:35,440 --> 00:49:36,320 IMMEDIATELY TREAT THESE PATIENTS 1257 00:49:36,320 --> 00:49:38,200 AND MAYBE WITH IMMUNOTHERAPY 1258 00:49:38,200 --> 00:49:42,120 APPROACHES BY THEMSELVES, WE CAN 1259 00:49:42,120 --> 00:49:44,440 SEE TUMORS THAT GO AWAY AND STAY 1260 00:49:44,440 --> 00:49:45,000 AWAY. 1261 00:49:45,000 --> 00:49:47,640 WHAT ARE THE OPPORTUNITIES HERE 1262 00:49:47,640 --> 00:49:52,080 IN BLADDER CANCER, AND HOW IS 1263 00:49:52,080 --> 00:49:53,440 THE FIELD CAPITALIZING ON SOME 1264 00:49:53,440 --> 00:49:54,160 OF THIS RESEARCH? 1265 00:49:54,160 --> 00:49:54,720 >> THANK YOU. 1266 00:49:54,720 --> 00:49:56,400 THANK YOU FOR ASKING ME THIS. 1267 00:49:56,400 --> 00:49:59,160 THIS IS SOMETHING THAT I HAVE 1268 00:49:59,160 --> 00:50:02,880 BEEN WORKING ON IN DEVELOPING 1269 00:50:02,880 --> 00:50:04,960 THROUGH THE COOPERATIVE GROUP. 1270 00:50:04,960 --> 00:50:07,560 AND WE HAVE A PROTOCOL IN 1271 00:50:07,560 --> 00:50:10,080 DEVELOPMENT RIGHT NOW TO SPARE 1272 00:50:10,080 --> 00:50:12,000 PATIENTS FROM UNDERGOING THESE 1273 00:50:12,000 --> 00:50:13,840 RADICAL SURGERIES, BUT ONLY FOR 1274 00:50:13,840 --> 00:50:17,040 PATIENTS THAT ARE MSI HIGH, OR 1275 00:50:17,040 --> 00:50:20,200 HAVE MISMATCHED REPAIR 1276 00:50:20,200 --> 00:50:21,040 DEFICIENCY, WHICH FOR BLADDER 1277 00:50:21,040 --> 00:50:23,440 CAN SE IT'S A SMALL PERCENTAGE, 1278 00:50:23,440 --> 00:50:25,680 IT'S 1 TO 2%, BUT FOR UPPER 1279 00:50:25,680 --> 00:50:27,840 TRACT TUMORS, IT'S ACTUALLY 8 TO 1280 00:50:27,840 --> 00:50:28,200 9%. 1281 00:50:28,200 --> 00:50:31,200 SO THE STUDY RIGHT NOW AS WE 1282 00:50:31,200 --> 00:50:33,840 HAVE IT PLANNED IS GOING TO 1283 00:50:33,840 --> 00:50:37,280 ENROLL ABOUT 800 TO 1,000 1284 00:50:37,280 --> 00:50:39,400 PATIENTS TO TREAT 50. 1285 00:50:39,400 --> 00:50:41,840 SO IT'S A BIG SCREENING EFFORT 1286 00:50:41,840 --> 00:50:44,360 IN ORDER TO FIND THOSE PATIENTS 1287 00:50:44,360 --> 00:50:47,960 THAT MAY BENEFIT FROM 1288 00:50:47,960 --> 00:50:49,040 IMMUNOTHERAPY WITHOUT UNDERGOING 1289 00:50:49,040 --> 00:50:50,200 THESE RADICAL SURGERIES. 1290 00:50:50,200 --> 00:50:51,720 SO THIS IS AN EFFORT THAT'S 1291 00:50:51,720 --> 00:50:52,920 ONGOING RIGHT NOW. 1292 00:50:52,920 --> 00:50:55,560 WE HAVE THE CONCEPT OF 1293 00:50:55,560 --> 00:50:57,040 PUT-THROUGH. 1294 00:50:57,040 --> 00:50:59,080 IT'S BEEN PRELIMINARILY APPROVED 1295 00:50:59,080 --> 00:51:01,400 BY THE COMPANY, AND WE HAVE A 1296 00:51:01,400 --> 00:51:03,040 MEETING NEXT WEEK WITH THE 1297 00:51:03,040 --> 00:51:04,040 ALLIANCE TO DISCUSS IT SOME 1298 00:51:04,040 --> 00:51:05,440 MORE. 1299 00:51:05,440 --> 00:51:06,960 BUT THAT'S FOR A REALLY SMALL 1300 00:51:06,960 --> 00:51:07,720 GROUP OF PATIENTS. 1301 00:51:07,720 --> 00:51:11,160 THAT'S FOR PATIENTS THAT HAVE 1302 00:51:11,160 --> 00:51:12,560 MISMATCH REPAIR DEFICIENCY, 1303 00:51:12,560 --> 00:51:14,880 WHICH IS A REALLY SPECIAL 1304 00:51:14,880 --> 00:51:15,640 PATIENT POPULATION. 1305 00:51:15,640 --> 00:51:18,600 THERE HAVE BEEN SO MANY EFFORTS 1306 00:51:18,600 --> 00:51:21,200 RIGHT NOW THAT ARE IN PLACE AND 1307 00:51:21,200 --> 00:51:23,400 ARE ONGOING LOOKING INTO ALL 1308 00:51:23,400 --> 00:51:24,440 BLADDER CANCERS. 1309 00:51:24,440 --> 00:51:27,280 WELL, WHAT ABOUT IF WE DO 1310 00:51:27,280 --> 00:51:28,840 RADIATION, WHAT ABOUT IF WE DO 1311 00:51:28,840 --> 00:51:32,160 CHEMO RADIATION, AND THEN NOT 1312 00:51:32,160 --> 00:51:35,560 TAKE THE BLADDER OUT AND HOW DO 1313 00:51:35,560 --> 00:51:39,720 THOSE PATIENTS DO, WE HAVE 1314 00:51:39,720 --> 00:51:40,920 SEVERAL TRIALS WITH TRI-MODALITY 1315 00:51:40,920 --> 00:51:42,920 THERAPY, WE CALL IT TRI-MODALITY 1316 00:51:42,920 --> 00:51:46,240 THERAPY, THAT HAVE SHOWN THAT 1317 00:51:46,240 --> 00:51:48,640 PATIENTS CAN HAVE A GOOD LIFE 1318 00:51:48,640 --> 00:51:50,920 WITH A RADIATED BLADDER, AND 1319 00:51:50,920 --> 00:51:52,680 HAVE GOOD FUNCTION AND KEEP 1320 00:51:52,680 --> 00:51:54,040 THEIR BLADDERS. 1321 00:51:54,040 --> 00:51:56,560 SO THERE'S A LOT OF INTEREST IN 1322 00:51:56,560 --> 00:51:58,080 IDENTIFYING WHO ARE THE BEST 1323 00:51:58,080 --> 00:51:59,040 PATIENTS, BECAUSE THERE'S THIS 1324 00:51:59,040 --> 00:52:00,440 RISK, RIGHT, THAT THEY'RE GOING 1325 00:52:00,440 --> 00:52:02,320 TO DEVELOP METASTATIC DISEASE, 1326 00:52:02,320 --> 00:52:03,960 SO WE HAVE THIS FEAR, CAN WE 1327 00:52:03,960 --> 00:52:06,040 SELECT THESE PATIENTS USING 1328 00:52:06,040 --> 00:52:07,560 BIOMARKERS, SO THERE'S A LOT OF 1329 00:52:07,560 --> 00:52:08,560 EFFORT IN THAT FIELD, AND THIS 1330 00:52:08,560 --> 00:52:11,560 IS SOMETHING THAT OUR UROLOGIC 1331 00:52:11,560 --> 00:52:12,760 ONCOLOGY COLLEAGUES AND OUR 1332 00:52:12,760 --> 00:52:14,640 RADIATION ONCOLOGY COLLEAGUES 1333 00:52:14,640 --> 00:52:17,640 ARE ALSO DISCUSSING ABOUT 1334 00:52:17,640 --> 00:52:23,600 DEVELOP AGO TRIAL HERE AING A TRIAL HERE A T THE 1335 00:52:23,600 --> 00:52:26,440 NCI TO A CYSTECTOMY-FREE STUDY 1336 00:52:26,440 --> 00:52:27,760 IN ORDER TO -- PATIENTS CAN KEEP 1337 00:52:27,760 --> 00:52:29,440 THEIR BLADDERS, WHICH IS REALLY 1338 00:52:29,440 --> 00:52:30,200 WHAT THEY WANT. 1339 00:52:30,200 --> 00:52:34,040 PATIENTS WANT TO KEAP THEIR KEEP THEIR 1340 00:52:34,040 --> 00:52:34,520 BLADDERS. 1341 00:52:34,520 --> 00:52:36,840 SO THERE ARE A LOT OF EFFORTS 1342 00:52:36,840 --> 00:52:38,040 ONGOING RIGHT NOW EVEN FOR 1343 00:52:38,040 --> 00:52:39,840 PATIENTS THAT DON'T HAVE DNA 1344 00:52:39,840 --> 00:52:42,440 REPAIR GENES, THAT DO NOT HAVE 1345 00:52:42,440 --> 00:52:44,960 MISMATCH REPAIR AND ARE NOT 1346 00:52:44,960 --> 00:52:45,240 MSI-HIGH. 1347 00:52:45,240 --> 00:52:46,520 >> RIGHT, AND I THINK THESE 1348 00:52:46,520 --> 00:52:47,400 EFFORTS WILL CONTINUE. 1349 00:52:47,400 --> 00:52:48,840 JUST ALSO FOR THE AUDIENCE WHO 1350 00:52:48,840 --> 00:52:50,640 MAY NOT BE AS FAMILIAR, JUST 1351 00:52:50,640 --> 00:52:52,680 GIVE US A LITTLE BIT ABOUT THE 1352 00:52:52,680 --> 00:52:56,360 UPPER TRACT DISEASE AND HOW THAT 1353 00:52:56,360 --> 00:52:59,440 TYPICALLY FAIRS COMPARED WITH 1354 00:52:59,440 --> 00:53:01,160 LOWER TRACT DISEASE. 1355 00:53:01,160 --> 00:53:03,920 >> THANK YOU FOR ASKING. 1356 00:53:03,920 --> 00:53:07,920 UPTRACT DISEASE, THERE WAS A -- 1357 00:53:07,920 --> 00:53:09,240 IT WAS FOR A LONG TIME THOUGHT 1358 00:53:09,240 --> 00:53:11,880 IT WAS MORE AGGRESSIVE THAN 1359 00:53:11,880 --> 00:53:13,840 BLADDER TUMORS, BUT THEN THERE'S 1360 00:53:13,840 --> 00:53:19,680 ALSO THISH YO THE ISSUE OF DIAGNOSING 1361 00:53:19,680 --> 00:53:20,160 UPPER TRACT DISEASE. 1362 00:53:20,160 --> 00:53:21,440 IT CAN BE VERY DIFFICULT TO 1363 00:53:21,440 --> 00:53:22,520 DIAGNOSE THESE, BECAUSE YOU KNOW 1364 00:53:22,520 --> 00:53:24,520 HOW I SHOWED YOU THE UROLOGIST 1365 00:53:24,520 --> 00:53:26,480 GOES IN AND TAKES A LOOK AT THE 1366 00:53:26,480 --> 00:53:28,560 BLADDER, GOING UP THE URETER IS 1367 00:53:28,560 --> 00:53:30,360 SO NARROW AND THEN LOOKING AT 1368 00:53:30,360 --> 00:53:32,760 THE RENAL PELVIS, IT'S SO EASY 1369 00:53:32,760 --> 00:53:35,920 TO MISS A TUMOR THAT IS IN THE 1370 00:53:35,920 --> 00:53:37,840 UPPER TRACT, SO A LOT OF TIMES 1371 00:53:37,840 --> 00:53:38,920 YOU'LL HAVE SOMETHING LIKE A 1372 00:53:38,920 --> 00:53:40,040 POSITIVE CYTOLOGY, WHICH IS A 1373 00:53:40,040 --> 00:53:42,160 URINE TEST THAT LOOKS AT CELLS, 1374 00:53:42,160 --> 00:53:43,640 BUT YOU DON'T SEE ANYTHING. 1375 00:53:43,640 --> 00:53:44,800 SO WHAT ARE YOU SUPPOSED TO DO? 1376 00:53:44,800 --> 00:53:47,520 SO IT'S VERY FRUSTRATING, AND 1377 00:53:47,520 --> 00:53:48,560 SCARY BECAUSE YOU FOLLOW THESE 1378 00:53:48,560 --> 00:53:51,920 PATIENTS WITH IMAGING AND WE 1379 00:53:51,920 --> 00:53:53,200 HAVE A TERRIFIC IMAGING PROGRAM 1380 00:53:53,200 --> 00:53:54,920 HERE WITH A LOT OF RADIOLOGISTS 1381 00:53:54,920 --> 00:53:56,160 INTERESTED IN BLADDER CANCER, SO 1382 00:53:56,160 --> 00:53:57,440 WE'RE VERY LUCKY, AND WE'RE 1383 00:53:57,440 --> 00:54:01,360 TRYING TO DEVELOP PROTOCOLS IN 1384 00:54:01,360 --> 00:54:03,000 ORDER TO DO SPECIFIC IMAGING 1385 00:54:03,000 --> 00:54:04,840 TECHNIQUES TO FOLLOW THESE 1386 00:54:04,840 --> 00:54:06,160 PATIENTS, AND LOOKING AT THE 1387 00:54:06,160 --> 00:54:07,960 UPPER TRACK WITH DELAYED 1388 00:54:07,960 --> 00:54:08,920 CONTRAST IMAGING TO SEE IF WE 1389 00:54:08,920 --> 00:54:12,520 CAN SEE MASSES, BUT WE REALLY 1390 00:54:12,520 --> 00:54:16,800 STRUGGLING IN THE INITIAL 1391 00:54:16,800 --> 00:54:17,560 DIAGNOSIS AND EVEN IN THE 1392 00:54:17,560 --> 00:54:17,960 BIOPSY. 1393 00:54:17,960 --> 00:54:23,560 I TOLD YOU WHEN WE BIOPSIED 1394 00:54:23,560 --> 00:54:24,240 PATIENTS UNDERGOING -- WE LOOK 1395 00:54:24,240 --> 00:54:25,040 AT DEPTH OF INNOVATION. 1396 00:54:25,040 --> 00:54:26,400 YOU CAN'T REALLY DO THAT IN THE 1397 00:54:26,400 --> 00:54:28,040 URETER AND RENAL PELVIS. 1398 00:54:28,040 --> 00:54:30,080 GETTING MUSCLE IS, YOU KNOW, 1399 00:54:30,080 --> 00:54:31,160 SOMETIMES IMPOSSIBLE AND 1400 00:54:31,160 --> 00:54:32,880 SOMETIMES DANGEROUS. 1401 00:54:32,880 --> 00:54:35,000 SO YOU'RE GOING TO GET SOMETHING 1402 00:54:35,000 --> 00:54:36,600 LIKE HYDRATE BUT YOU DON'T 1403 00:54:36,600 --> 00:54:37,640 KNOW -- WHAT DO YOU DO WITH 1404 00:54:37,640 --> 00:54:38,440 THESE PATIENTS? 1405 00:54:38,440 --> 00:54:44,480 SO FOR MUSCLE INVASIVE T2, T3, 1406 00:54:44,480 --> 00:54:46,240 FOR MUSCLE INVASIVE UPPER TRACT 1407 00:54:46,240 --> 00:54:48,280 TUMORS, WE REALLY STRUGGLED WITH 1408 00:54:48,280 --> 00:54:51,440 HOW TO MANAGE THESE PATIENTS IN 1409 00:54:51,440 --> 00:54:53,600 TERMS OF DO WE GIVE THEM CHEMO, 1410 00:54:53,600 --> 00:55:00,360 DO WE GIVE JUST T # PATIENT1 PATIENTS 1411 00:55:00,360 --> 00:55:01,040 CHEMO. 1412 00:55:01,040 --> 00:55:03,080 I WROTE A TRIAL FOR UPPER TRACT 1413 00:55:03,080 --> 00:55:05,000 TUMORS AND IT JUST GOT PUBLISHED 1414 00:55:05,000 --> 00:55:05,640 IN JCO. 1415 00:55:05,640 --> 00:55:07,600 IT TOOK A LONG TIME TO ACCRUE 1416 00:55:07,600 --> 00:55:08,680 BECAUSE IT'S LESS COMMON, SO IT 1417 00:55:08,680 --> 00:55:11,880 ONLY OCCURS IN ABOUT 10%, UPPER 1418 00:55:11,880 --> 00:55:13,640 TRACT TUMORS VERSUS REGULAR 1419 00:55:13,640 --> 00:55:15,080 BLADDER CANCER, SO ACCRUING TO 1420 00:55:15,080 --> 00:55:16,160 THESE TRIALS ARE VERY DIFFICULT 1421 00:55:16,160 --> 00:55:19,840 AND ALSO THE ELIGIBILITY IS VERY 1422 00:55:19,840 --> 00:55:21,240 DIFFICULT, ARE YOU OVERTREATING 1423 00:55:21,240 --> 00:55:22,480 SOME PATIENTS, NOT CORRECTLY 1424 00:55:22,480 --> 00:55:23,160 DIAGNOSING OTHERS. 1425 00:55:23,160 --> 00:55:26,840 BUT WE DO SEE THAT GETTING 1426 00:55:26,840 --> 00:55:27,640 CHEMOTHERAPY AT THE STAGE WHEN 1427 00:55:27,640 --> 00:55:29,200 YOU INITIALLY DIAGNOSED THEM 1428 00:55:29,200 --> 00:55:30,720 WITH A HIGH GRADE TUMOR IS GOOD 1429 00:55:30,720 --> 00:55:39,760 TO DO BEFORE YOU DO THE NE FRECT 1430 00:55:39,760 --> 00:55:40,840 NEPHRECTOMY, THEN THEY ONLY HAVE 1431 00:55:40,840 --> 00:55:42,640 ONE KIDNEY, WE'RE GIVING THEM 1432 00:55:42,640 --> 00:55:43,880 SOMETHING VERY TOXIC TO THE 1433 00:55:43,880 --> 00:55:45,280 KIDNEY SO CAN WE DO IT BEFORE. 1434 00:55:45,280 --> 00:55:46,160 SO THIS ANSWERED THIS QUESTION, 1435 00:55:46,160 --> 00:55:47,040 CAN WE DO IT BEFORE. 1436 00:55:47,040 --> 00:55:48,840 BUT WHEN IT COMES TO METASTATIC 1437 00:55:48,840 --> 00:55:50,800 DISEASE, UPPER TRACT TUMORS HAVE 1438 00:55:50,800 --> 00:55:55,640 VERY SIMILAR OUTCOMES THAN 1439 00:55:55,640 --> 00:55:57,040 BLADDER PRIMARIES WHEN IT'S 1440 00:55:57,040 --> 00:55:59,880 METASTATIC, WHEN IT'S OUTSIDE IN 1441 00:55:59,880 --> 00:56:01,000 THE VISCERAL ORGANS. 1442 00:56:01,000 --> 00:56:02,320 AND WE TREAT IT THE SAME IN 1443 00:56:02,320 --> 00:56:03,640 TERMS OF THE SYSTEMIC THERAPIES 1444 00:56:03,640 --> 00:56:04,800 THAT WE HAVE AVAILABLE FOR THE 1445 00:56:04,800 --> 00:56:06,600 PATIENTS. 1446 00:56:06,600 --> 00:56:07,520 >> RIGHT. 1447 00:56:07,520 --> 00:56:10,240 JUST HIGHER LIKELIHOOD OF BEING 1448 00:56:10,240 --> 00:56:11,480 MSI-YOU HI. 1449 00:56:11,480 --> 00:56:11,800 LOOKS GOOD. 1450 00:56:11,800 --> 00:56:15,640 >-HIGH. 1451 00:56:15,640 --> 00:56:15,840 >> YES. 1452 00:56:15,840 --> 00:56:19,040 >> IT IS RARE WHEN A TENURE 1453 00:56:19,040 --> 00:56:21,160 TRACT DOES A FIRST IN HUMAN 1454 00:56:21,160 --> 00:56:23,760 STUDY THAT LEADS TO A PHASE III 1455 00:56:23,760 --> 00:56:25,440 STUDY THAT LEADS TO APPROVAL, 1456 00:56:25,440 --> 00:56:29,000 AND IT'S EVEN MORE RARE WHEN YOU 1457 00:56:29,000 --> 00:56:30,960 HAVE TWO DRUGS THAT YOU'VE BEEN 1458 00:56:30,960 --> 00:56:33,040 ASSOCIATED WITH, COMBINATIONS 1459 00:56:33,040 --> 00:56:34,800 YOU'VE BEEN ASSOCIATED WITH, 1460 00:56:34,800 --> 00:56:37,480 FIRST IN HUMAN COMBINATION OR 1461 00:56:37,480 --> 00:56:41,040 FIRST IN HUMAN -- LED TO FDA 1462 00:56:41,040 --> 00:56:42,600 APPROVAL, WHICH IS FANTASTIC. 1463 00:56:42,600 --> 00:56:43,720 I WANT TO ASK YOU A LITTLE BIT 1464 00:56:43,720 --> 00:56:45,640 ABOUT THE DATA THAT YOU HAD WITH 1465 00:56:45,640 --> 00:56:54,520 THE CABO-NS-NIBO. 1466 00:56:54,520 --> 00:56:56,040 YOU SAW ACTIVITY ACROSS A 1467 00:56:56,040 --> 00:56:58,640 SPECTRUM OF G.U. CANCERS, BUT 1468 00:56:58,640 --> 00:57:01,240 YOU SAW ACTIVITY IN RENAL AND IN 1469 00:57:01,240 --> 00:57:02,720 BLADDER, BUT NOT SO MUCH IN 1470 00:57:02,720 --> 00:57:03,360 PROSTATE. 1471 00:57:03,360 --> 00:57:05,840 AND I KNOW THERE'S FEW PATIENTS 1472 00:57:05,840 --> 00:57:07,320 THERE, BUT WHAT ARE YOUR 1473 00:57:07,320 --> 00:57:08,120 THOUGHTS THERE? 1474 00:57:08,120 --> 00:57:09,760 WERE THESE JUST SICKER PATIENTS 1475 00:57:09,760 --> 00:57:12,320 OR WAS IT A TUMOR MUTATION 1476 00:57:12,320 --> 00:57:13,960 BURDEN OR IS THERE SOMETHING 1477 00:57:13,960 --> 00:57:15,520 INTRINSIC IN PROSTATE CANCER 1478 00:57:15,520 --> 00:57:18,600 THAT DOESN'T LEND ITSELF TO THIS 1479 00:57:18,600 --> 00:57:21,520 APPROACH WHERE WE KNOW WITH 1480 00:57:21,520 --> 00:57:24,040 KIDNEY CANCER, FOR INSTANCE, WE 1481 00:57:24,040 --> 00:57:30,280 DO HAVE PEMBROLIZUMAB AND 1482 00:57:30,280 --> 00:57:31,760 AVELUMAB AND -- APPROVED FOR 1483 00:57:31,760 --> 00:57:35,360 KIDNEY CANCER, SO IT MAKES SENSE 1484 00:57:35,360 --> 00:57:38,200 THAT AN ANTIANGIOGENESIS AGENT 1485 00:57:38,200 --> 00:57:40,400 WITH IMMUNE CHECKPOINT INHIBITOR 1486 00:57:40,400 --> 00:57:41,440 MAY ALSO WORK WITH KIDNEY 1487 00:57:41,440 --> 00:57:42,520 CANCER, BUT WHAT ABOUT THESE 1488 00:57:42,520 --> 00:57:43,240 OTHER CANCERS? 1489 00:57:43,240 --> 00:57:45,080 >> I THINK THAT'S A GREAT 1490 00:57:45,080 --> 00:57:45,960 QUESTION, AND THE TRUTH IS, I 1491 00:57:45,960 --> 00:57:47,440 DON'T KNOW. 1492 00:57:47,440 --> 00:57:50,360 YOU KNOW, I THINK THAT THIS HAS 1493 00:57:50,360 --> 00:57:52,680 BEEN AN INTEREST OF MANY OF MY 1494 00:57:52,680 --> 00:57:56,640 COLLEAGUES, INCLUDING YOU AND 1495 00:57:56,640 --> 00:57:58,040 OTHER COLLEAGUES AT THE NCI 1496 00:57:58,040 --> 00:58:00,120 TRYING TO UNDERSTAND THE 1497 00:58:00,120 --> 00:58:01,400 MICROENVIRONMENT IN PROSTATE 1498 00:58:01,400 --> 00:58:06,320 CANCER TUMORS, AND HOW CAN WE 1499 00:58:06,320 --> 00:58:07,640 SIMULATE IT SO CHECKPOINT 1500 00:58:07,640 --> 00:58:08,840 INHIBITORS WORK, BECAUSE WHEN 1501 00:58:08,840 --> 00:58:12,960 THEY DO WORK, THEY WORK SO WELL. 1502 00:58:12,960 --> 00:58:17,200 ONE OTHER FACTOR, TOO, IN ALL 1503 00:58:17,200 --> 00:58:19,160 FAIRNESS IS PROSTATE TUMORS ARE 1504 00:58:19,160 --> 00:58:20,720 HARD TO MEASURE. 1505 00:58:20,720 --> 00:58:22,120 AND THE PATIENTS THAT I HAD 1506 00:58:22,120 --> 00:58:24,200 THERE IN THE WATERFALL PLOT HAD 1507 00:58:24,200 --> 00:58:26,240 LYMPH NODE DISEASE, AND IF IT'S 1508 00:58:26,240 --> 00:58:27,440 BONE-ONLY DISEASE, YOU CAN'T 1509 00:58:27,440 --> 00:58:29,080 REALLY DO THOSE WATERFALL PLOTS 1510 00:58:29,080 --> 00:58:31,120 BECAUSE YOU CAN'T MEASURE A 1511 00:58:31,120 --> 00:58:31,440 RESPONSE. 1512 00:58:31,440 --> 00:58:33,440 SO ASSESSING RESPONSE IN 1513 00:58:33,440 --> 00:58:34,040 PROSTATE CANCER PATIENTS HAS 1514 00:58:34,040 --> 00:58:37,280 BEEN A STRUGGLE, AND WE DO HAVE 1515 00:58:37,280 --> 00:58:42,080 PSA, WHICH IS GREAT, BUT REALLY 1516 00:58:42,080 --> 00:58:43,960 ASSESSING TUMOR BURDEN AND 1517 00:58:43,960 --> 00:58:49,960 RESPONSE TO THERAPY HAS BEEN 1518 00:58:49,960 --> 00:58:51,120 SOMETHING THAT I THINK HAS BEEN 1519 00:58:51,120 --> 00:58:52,440 ANOTHER AREA WHERE I THINK 1520 00:58:52,440 --> 00:58:54,720 IMAGING HAS TAKEN A VERY 1521 00:58:54,720 --> 00:58:55,840 IMPORTANT ROLE IN COMBINATION 1522 00:58:55,840 --> 00:58:58,480 WAYS WITH BIOMARKERS, PSA LEVELS 1523 00:58:58,480 --> 00:59:00,040 AND IMAGING TOGETHER IN ORDER TO 1524 00:59:00,040 --> 00:59:00,920 REALLY ASSESS WHETHER SOMEBODY 1525 00:59:00,920 --> 00:59:01,960 IS RESPONDING OR NOT. 1526 00:59:01,960 --> 00:59:04,920 BUT I DON'T KNOW WHY CERTAIN 1527 00:59:04,920 --> 00:59:07,440 TUMORS ARE MORE SUSCEPTIBLE TO 1528 00:59:07,440 --> 00:59:09,240 IMMUNOTHERAPY AND HOW CAN WE 1529 00:59:09,240 --> 00:59:11,440 MAKE CERTAIN TUMORS MORE 1530 00:59:11,440 --> 00:59:12,840 ACCESSIBLE TO IMMUNOTHERAPY, I 1531 00:59:12,840 --> 00:59:14,600 THINK THESE ARE ALL GREAT 1532 00:59:14,600 --> 00:59:15,280 RESEARCH QUESTIONS THAT ARE 1533 00:59:15,280 --> 00:59:16,840 ONGOING RIGHT NOW. 1534 00:59:16,840 --> 00:59:18,040 >> WELL, FANTASTIC. 1535 00:59:18,040 --> 00:59:20,720 I THINK WE'RE OUT OF TIME NOW. 1536 00:59:20,720 --> 00:59:22,240 WE'RE JUST EXACTLY AT 1:00. 1537 00:59:22,240 --> 00:59:24,440 THIS WAS JUST SUCH AN AMAZING 1538 00:59:24,440 --> 00:59:28,080 PRESENTATION, AND COP GRAT AND 1539 00:59:28,080 --> 00:59:28,880 CONGRATULATIONS ON YOUR TENURE. 1540 00:59:28,880 --> 00:59:29,840 >> THANK YOU SO MUCH. 1541 00:59:29,840 --> 00:59:33,280 >> MANY, MANY THANKS, ANDREA, 1542 00:59:33,280 --> 00:59:35,880 FOR A REAL TOUR DEFORCE, AND 1543 00:59:35,880 --> 00:59:37,320 THANKS, JAMES, FOR STARTING A 1544 00:59:37,320 --> 00:59:39,040 DISCUSSION THAT I THINK REALLY 1545 00:59:39,040 --> 00:59:40,600 ILLUMINATED SOME OF THE 1546 00:59:40,600 --> 00:59:42,760 IMPORTANT POINTS OF THE TALK. 1547 00:59:42,760 --> 00:59:46,200 I WANT TO THANK ALEX AND KENNY 1548 00:59:46,200 --> 00:59:50,160 AND KIM PUBLICLY FOR MAKING THIS 1549 00:59:50,160 --> 00:59:53,640 GO LIVE, AND ALL OF YOU WHO HAVE 1550 00:59:53,640 --> 00:59:55,840 TUNED IN, MANY THANKS FOR 1551 00:59:55,840 --> 00:59:56,800 LISTENING, AND I HOPE YOU'LL 1552 00:59:56,800 --> 01:00:01,600 JOIN US WITH FUTURE DIRECTOR 1553 01:00:01,600 --> 01:00:01,880 SEMINARS. 1554 01:00:01,880 --> 01:00:03,920 AND A SPECIAL THANKS AND HAPPY 1555 01:00:03,920 --> 01:00:05,040 BIRTHDAY TO DR. MICHAEL 1556 01:00:05,040 --> 01:00:06,440 GOTTESMAN. 1557 01:00:06,440 --> 01:00:07,440 THANKS FOR JOINING US, 1558 01:00:07,440 --> 01:00:08,760 EVERYBODY. 1559 01:00:08,760 --> 00:00:00,000 >> HAPPY BIRTHDAY, DR. GOTTESMAN