Abstract
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).