A phase I study of cabozantinib plus nivolumab (CaboNivo) and cabonivo plus ipilimumab (CaboNivoIpi) in patients (pts) with refractory metastatic (m) urothelial carcinoma (UC) and other genitourinary (GU) tumors.

Abstract

4562 Background: We report the safety and clinical activity of the combination of CaboNivo and CaboNivoIpi in pts with mUC and other mGU tumors (NCT02496208). Methods: In this phase I trial 30 pts were treated in 4 dose levels (DL) for part 1 (CaboNivo) and 18 pts were treated in 3 DL for part 2 (CaboNivoIpi). Pts received Cabo PO daily and Nivo IV (part 1) with Ipi 1mg/kg x 4 doses q3wks (part 2). A mUC and a renal cell carcinoma (RCC) expansion cohort of CaboNivo has initiated enrollment. Tumors were assessed for overall response rate (ORR) q8wks (RECIST 1.1). Adverse events (AEs) were graded (G) by NCI-CTCAE v4.0. Results: From 7/22/15 to 12/31/2016, 48pts (CaboNivo N = 30; CaboNivoIpi N = 18) (mUC N = 19; bladder urachal N = 4; bladder squamous cell carcinoma (bSCC) N = 2; germ cell tumor (GCT) N = 4; castrate-resistant prostate cancer (CRPC) N = 9; RCC N = 2, sarcomatoid RCC N = 2, Sertoli cell N = 1, and trophoblastic tumor N = 1 were treated. Median age was 58 (range 35-77), 41 (85%) were male. Common treatment-related G1/2 AEs for CaboNivo: ALT increase (67%), fatigue (63%), diarrhea (60%), hypothyroidism (57%); CaboNivoIpi: fatigue (72%), diarrhea (61%), anorexia (61%); Grade 3 AEs for CaboNivo: hypertension (23%), neutropenia (17%), hypophosphatemia (13%), lipase increase (10%), fatigue (7%), aseptic meningitis (3%); CaboNivoIpi: hypophosphatemia (19%), hypertension (19%), fatigue (13%), hyponatremia (13%), nausea (13%), lipase increase (11%), colitis (6%); G4 CaboNivo: lipase increase (7%) thrombocytopenia (3%); CaboNivoIpi lipase increase (6%) There were no G5 toxicities, no DLTs. 43 pts were evaluable for response: ORR was 30% 13/43 [3 CR (2 mUC, 1 bSCC); 10 PRs (4 mUC, 2 penile, 1 sarcomatoid RCC, 1 urachal, 1 CRPC, 1 bSCC)]. ORR for CaboNivo 39% (mUC 44%); CaboNivoIpi 18% (mUC 29%). 11/13 (85%) of responses were ongoing at cutoff. Conclusions: CaboNivo and CaboNivoIpi combinations were well tolerated with no DLTs and have durable efficacy in mGU tumors particularly mUC. Rare tumors such as bSCC, urachal, and penile cancers demonstrated response to the combination. Larger cohorts of mUC and rare GU tumors are ongoing. Clinical trial information: NCT02496208.