Clinical Data A phase I study of cabozantinib plus nivolumab (CaboNivo) inpatients (pts) refractory metastatic urothelial carcinoma(mUC) and other genitourinary (GU) tumors

Results: From 7/22/15-5/11/16, 24pts (mUC N = 6; bladder urachal N = 4; bladdersquamous cell carcinoma (SCC) N = 3; germ cell tumor (GCT) N = 5; castrate-resistantprostate cancer (CRPC) N = 4; renal cell carcinoma (RCC) N = 1, and trophoblastictumor N = 1) were treated. Median age was 55 (range 35-75), 21 (88%) were male. 9 ptsrequired dose reductions (N = 2 DL1; N = 1 DL2; N = 2 DL3; N = 4 DL4), for PPE G2N = 3 (DL1/2/4)); fatigue G1/2 N = 2 (DL3), diarrhea G2 N = 1 (DL3), lipase/amylaseelevation G3 (DL1), weight loss G1 N = 1 (DL4), and anorexia/dehydration G2 N = 2(DL4). Common treatment-related G1/2 AEs were transaminitis N = 20, diarrheaN = 11, hoarseness N = 7, dysgeusia N = 5, thrombocytopenia N = 5, hyponatremiaN = 5. Grade 3 AEs included neutropenia N = 3 (DL1), fatigue N = 2 DL2, mucositisN = 1 (DL4), vomiting N = 1 (DL3). There were no G4/5 toxicities, no immune-relatedAEs and no DLTs. 18 pts were evaluable for response. ORR was 33% 6/18 (1 CR(bladder SCC); 5 PRs (mUC, RCC, urachal, urethral SCC, CRPC). All responses wereongoing at cutoff. SD 38% 7/18.Conclusions: CaboNivo was well tolerated with no DLTs. Cabo 60mg resulted in moredose reductions due to clinically significant AEs. The recommended dose isCabo40mg/Nivo3mg/kg. Part II of the phase I (triplet with ipilimumab (CaboNivoIpi)is ongoing. Expansion studies in pts with mUC and RCC are planned.