Circulating tumor cell (CTC) enumeration in patients (pts) with metastatic genitourinary (mGU) tumors treated in a phase I study of cabozantinib and nivolumab (CaboNivo) +/- ipilimumab (CaboNivoIpi).

4555 Background: CTCs may serve as biomarkers for clinical outcomes in GU tumor pts. We examined the association between baseline CTC enumeration, CTC heterogeneity, CTC morphologic subtypes, and progression-free-survival, overall survival and response to therapy with combination CaboNivo or CaboNivoIpi. Methods: 123 samples from 52 pts with mGU tumors treated with CaboNivo (38 pts) or CaboNivoIpi (14 pts) drawn at Baseline, Cycle (C) 2 Day (D) 1, and C3D1 were processed using the Epic Sciences platform. CTCs were defined as cytokeratin (CK)+, CD45-, distinct morphology, intact nucleus. PD-L1 expression was also assessed. Results: From 07/20/2016-09/01/2018, 52 pts [urothelial carcinoma (UC) N = 33; plasmacytoid N = 1; Clear cell renal cell carcinoma N = 4; bladder adenocarcinoma N = 8; bladder squamous cell carcinoma N = 2; bladder small cell N = 2; renal medullary N = 2] were treated. Median age was 61.5 years (range 20-82); 35 (67%) were male. N = 37 (71%) had visceral involvement, N = 15 (29%) with liver involvement, N = 11 (21%) with bone involvement. CTCs were found in the peripheral blood of 26/40 (65%) pts at baseline. 1/40 pts (bladder adenocarcinoma) had PDL1+ CTCs at Baseline. Median CTC/mL at Baseline, C2D1, C3D1, were not significantly different. CTC counts of > 2 and > 4 at C2D1 were potentially associated with shorter OS (p = 0.071 and p = 0.045 without adjustment for multiple cutoffs for evaluation). PFS results exhibited similar trends. Unsupervised clustering of CTC images identified 5 main CTC subtypes, of which the presence of one was significantly associated with shorter OS (p = 0.0014, not adjusted for multiple testing). Additionally, we observed a trend towards patients with higher CTC heterogeneity at C2D1 having longer OS, when adjusting for the risk associated with CTC enumeration (p = 0.084). Conclusions: CTC were detected in pts with mGU tumors treated with CaboNivo and CaboNivoIpi. CTC values were somewhat but not statistically lower in responders vs. non-responders. On treatment lower CTCs and the absence of aggressive CTC subtypes were associated with better clinical outcomes. Ongoing analyses include single cell genomics, and analysis of T-cell populations. Clinical trial information: NCT02496208.