Phase 1b study of intravenous coxsackievirus A21 (V937) and ipilimumab for patients with metastatic uveal melanoma

Purpose No standard of care therapy exists for patients with metastatic uveal melanoma who are not HLA-A2:01 positive. The phase 1b, open-label CLEVER study (NCT03408587) evaluated V937 in combination with ipilimumab in patients with uveal melanoma. Methods Adults with advanced uveal melanoma and liver metastases received up to 8 cycles of intravenous V937 (1 × 10 9 TCID 50 per infusion; infusions on days 1, 3, 5, and 8 [cycle 1], then every 3 weeks [Q3W] thereafter [cycles 2–8]) and 4 cycles of intravenous ipilimumab 3 mg/kg Q3W (beginning at cycle 1 day 8). The primary endpoint was safety. Secondary endpoints included objective response rate and progression-free survival (PFS) per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Results Eleven patients were enrolled (median age, 65.0 years) and received a median of 6 injections of V937 and 3.5 infusions of ipilimumab. The best overall response was stable disease in 3 patients and progressive disease in 8 patients. All patients exhibited progression per irRECIST, with a 9% irPFS rate at week 26. Ten patients had treatment-related AEs, the most frequent of which were diarrhea (55%), fatigue (45%), and myalgia (36%). Two grade 3 AEs (diarrhea, n = 2) were considered related to ipilimumab; neither was related to V937. Conclusion Although the combination of V937 with ipilimumab had a manageable safety profile, meaningful clinical benefit was not observed in patients with uveal melanoma and liver metastases. Trial registration ClinicalTrials.gov, NCT03408587 (January 24, 2018).