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).

379 Background: CTCs may serve as biomarkers for clinical outcomes in GU tumor pts. We examined the association between baseline CTC enumeration, change in CTC enumeration post treatment, progression-free-survival, overall survival and response to therapy with combination CaboNivo or CaboNivoIpi. Methods: 128 samples from 52 pts with mGU tumors treated with CaboNivo (38 pts) or CaboNivoIpi (14 pts) were drawn at baseline, cycle (C) 2 Day (D) 1, and C3D1 and processed with Epic Sciences platform. CTCs were defined as cytokeratin (CK)+, CD45-, distinct morphology, intact nucleus. PD-L1 expression was assessed. Results: From 07/20/2016-09/01/2018, 52 pts were treated for metastatic [urothelial carcinoma (UC) N = 33; UC plasmacytoid N = 1; clear cell renal cell carcinoma N = 4; bladder adenocarcinoma (BAC) N = 8; bladder squamous cell carcinoma N = 2; bladder small cell carcinoma N = 2; renal medullary carcinoma N = 2]. Median age was 61.5 years (range 20-82); 35 (67%) were male; N = 37(71%) had visceral involvement, N = 15(29%) had liver involvement, N = 11(21%) had bone involvement. CTCs were found in the peripheral blood of 39 (75%) pts, 1 pt (BAC) had PDL1+ CTCs at baseline. Median CTC/mL at C1D1, C2D1, C3D1, were 0.5 (0-357.1), 0.4 (0-71.8), and 0.75 (0-18), respectively. Median (lower and upper quartile) CTCs in pts with complete or partial responses (responders) vs stable or progressive disease (non-responders) were: 0.0 (0 to 5.40) vs 0.7 (0 to 2.5) at baseline; -0.35 (-3.65 to 0) vs 0 (-2 to 1.7) change from baseline to C2D1; and 0 (-5.4 to 0.5) vs 0 (-0.9 to 0.65) change from baseline to C3D1 (all p > 0.15). 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. Conclusions: CTC were detected in pts with mGU tumors treated with CaboNivo and CaboNivoIpi. CTC values were lower in responders than in non-responders. On treatment lower CTCs were associated with better clinical outcomes. Ongoing analyses with the CTCs include cell morphology and heterogeneity, single cell genomics, and T-cell populations.