We report the updated safety and efficacy of CaboNivo and CaboNivoIpi in pts with mUC and other GU tumors (NCT02496208).
Primary objective was to determine the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D). We tested 7 dose levels (DL); 4 in part 1 (CaboNivo); 3 in part 2 (CaboNivoIpi). Part 1 pts received cabo PO daily/Nivo IV q2wks: DL1 Cabo 40mg/Nivo 1mg/kg, DL2 Cabo 40mg/Nivo 3mg/kg, DL3 Cabo 60mg/Nivo1mg/kg, DL4 Cabo 60mg/Nivo 3mg/kg. Part 2 pts received Cabo PO daily/Nivo/Ipi IV q3wks x4 cycles → Nivo IV q2wks: DL5 Cabo 40mg/Nivo1&Ipi 1mg/kg, DL6 Cabo 40mg/Nivo 3&Ipi 1mg/kg, DL7 Cabo 60mg/Nivo3&Ipi 1mg/kg. Adverse events (AEs) were graded by CTCAE v4.0. Other objectives: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
From 07/15/2015-04/25/2017, median(m) potential follow-up: 13.4 months(mo). 42 pts enrolled: 24 pts in part 1 (mUC n = 7; urachal (Ur) n = 4; germ cell tumor n = 4; prostate cancer (PC) n = 4; bladder squamous cell carcinoma (bSCC) n = 2; penile n = 1; sarcomatoid renal cell carcinoma (sRCC) n = 1; and trophoblastic n = 1); 18 pts in part 2 (mUC n = 8; penile n = 3; CRPC n = 5; sertoli n = 1; sRCC n = 1). Median age: 56 years (range 31-77), 90.5% male. Grade 3–4 AEs occurred in 67% of pts, mostly in part 1: hypophosphatemia (21%), neutropenia (21%), fatigue (12%), elevated lipase (12%); diarrhea, hypertension (HTN), dehydration, thrombocytopenia, proteinuria, and leukopenia (8% each); in part 2: hypophosphatemia (22%) HTN (17%); fatigue, nausea, lymphopenia, and elevated lipase (11% each). G3 immune-related AEs: aseptic meningitis (n = 1, DL1) and colitis (n = 1, DL5). No G5 toxicities or DLTs. RP2D for part 1: Cabo40mg/Nivo3mg/kg; for part 2: Cabo40mg/Nivo3&Ipi1mg/Kg. ORR=35%, 3CR (2mUC, 1SCC) & 11PR (3mUC, 2SCC, 2sRCC, 2Penile, 1Ur, 1PC). mDOR (CR+PR+SD): 7.1 mo [95% CI: 5.1-not reached], mPFS: 5.5 mo [95%CI: 4.5-12.8] and mOS was not reached. OS at 6&12 mo was 83.3%&64.3%.
CaboNivo and CaboNivoIpi showed durable clinical activity in mUC and rare GU malignancies with manageable toxicity.
Clinical trial identification
Trial Protocol Number: NCT02496208, release date: 07/15/2015
Legal entity responsible for the study
National Cancer Institute, National Health Institutes.
Cancer Therapy Evaluation Program
All authors have declared no conflicts of interest.