Initial results of a phase II study of nivolumab(N) and ipilimumab(I) in genitourinary malignancies with neuroendocrine differentiation.

569 Background: Patients with metastatic genitourinary malignancies with neuroendocrine have limited therapeutic options following platinum therapy. Given encouraging results in initial cohort analysis for small cell urinary tract carcinoma, a cohort of any genitourinary malignancy with neuroendocrine differentiation was added to a multicenter, single arm, multi-cohort phase II trial to evaluate the efficacy of N and I in this setting. (NCT 03333616) Methods: Eligible patients had metastatic or locally advanced genitourinary malignancy with neuroendocrine differentiation with an ECOG performance status of 0-2; they may have received any line of prior therapy excluding prior immunotherapy. Patients underwent baseline biopsy and received treatment with N 3 mg/kg and I 1 mg/kg intravenously every 3 weeks for 4 cycles with continued maintenance of N 480 mg IV every 4 weeks. Imaging was performed at 12 weeks and then every 8 weeks through month 6 and then every 12 weeks thereafter. The primary endpoint was investigator assessed objective response rate (ORR) by RECIST 1.1. Results: A total of 27 patients were enrolled between 06/27/2018 and 06/21/2021, 10 (37%) had urinary tract cancer and 17 (63%) had prostate cancer (19 in expansion cohort, 3 urinary tract and 5 prostate cancer from earlier cohorts). The majority (n=25, 93%) patients received prior systemic therapy. Nine (33%) patients received all 4 doses of N and I during the induction period. Nine (33%) patients (7 of whom received 4 cycles N+I) received N maintenance (median number of cycles 9 (range, 2-37)). Median follow-up was 6.8 (range, 0.9-37.3) months. Objective response was achieved in 8 (30%, 80% CI 18%-44%) patients (Table). Median duration of response was not reached with 4 patients maintaining response >9 months. Median progression-free survival time was 2.6 (95% CI 1.8-6.5) months At time of analysis, 13 (48%) death events were reported due to progressive disease, in which 3 were bladder and 10 were prostate cancer. 8 (30%) patients developed treatment-related grade 3 or higher toxicities; one grade 5 toxicity was deemed treatment-unrelated. Conclusions: In this study we demonstrate N+I resulted in objective responses in patients with genitourinary malignancy with neuroendocrine differentiation. ORR of 50% in small cell carcinoma is bladder cancer is noteworthy and will be evaluated further in ongoing expansion cohort of bladder or upper tract carcinoma with variant histology. Clinical trial information: NCT03333616. [Table: see text]