Phase II multicenter, single arm, open label study of nivolumab in combination with ipilimumab in untreated patients with metastatic uveal melanoma (GEM1402.NCT02626962)

Abstract

Background: Uveal melanoma (UM) accounts for 0.1% of cancer-related deaths. Liver disease is the most common finding. Life expectancy is reduced (<9 months) and chemotherapy seems not to improve overall survival (OS). Nivolumab plus ipilimumab (NIVO+IPI) has showed efficacy in metastatic skin melanoma, but to date no evidence on metastatic UM (MUM) is available. Methods: GEM1402 is a phase-II, single-arm trial, leaded by the Spanish Melanoma Group (GEM) on NIVO+IPI in 50 untreated pts with MUM and ECOG-PS 0/1, recruited in 10 Spanish Sites. NIVO (1mg/kg, q3wk) and IPI (3mg/kg q3wk) were administered during 4 inductions, followed by NIVO (3mg/kg q2wk) until progressive disease (PD), toxicity or withdrawal. OS, progression free survival (PFS), overall response rate (ORR) per RECIST 1.1 (q6wk), and safety were evaluated. Intention to treat analysis includes pts with PD at first radiological evaluation. All pts receiving at least one dose of study treatment were evaluable for safety. Final data is disclosed. Results: A total of 50 of 52 pts enrolled from April 2016 to May 2017 were analyzed. Median age 59 (26-84), 48% male, liver M1 in 76% pts, extra-liver M1 in 56% pts, 32% elevated LDH. 33 pts completed 2 cycles and 7 pts stopped after 1 dose (6 PD, 1 toxicity). Treatment-related adverse events were reported in 46 pts and treatment discontinuation in 9 pts. G ≥ 3 toxicities were reported in 27 pts (54%): transaminitis, dermatological, hepatitis, diarrhea, neurological, anemia, thyroiditis, hyperthyroidism, hypophysitis and hyponatremia. All G3/4 were resolved following the related guidelines. A G5 acute thyroiditis related to NIVO+IPI was reported. ORR was 6/50(12%)(95%CI 3-21), disease stabilization in 26/50(52%) and Disease Control Rate was 64% (95%CI 50.7-77.3). With a median follow-up of 7.06m, PFS was 3.27m. Median OS was 12.7 months. Conclusions: Combination of NIVO+IPI is feasible in terms of efficacy and toxicity for MUM that merit further investigation. Clinical trial identification: EudraCT:201500442915. Legal entity responsible for the study: Grupo Español Multidisciplinar de Melanoma. Funding: Bristol-Myers Squibb (BMS). Disclosure: All authors have declared no conflicts of interest.