Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study

Abstract

Purpose: Metastatic uveal melanoma has poor overall survival (OS) and no approved systemic therapy options. Studies of single-agent immunotherapy regimens have shown minimal benefit. There is the potential for improved responses with the use of combination immunotherapy.

Patients and methods: We conducted a phase II study of nivolumab with ipilimumab in patients with metastatic uveal melanoma. Any number of prior treatments was permitted. Patients received nivolumab 1 mg/kg and ipilimumab 3 mg/kg for four cycles, followed by nivolumab maintenance therapy for up to 2 years. The primary outcome of the study was overall response rate (ORR) as determined by RECIST 1.1 criteria. Progression-free survival (PFS), OS, and adverse events were also assessed.

Results: Thirty-five patients were enrolled, and 33 patients were evaluable for efficacy. The ORR was 18%, including one confirmed complete response and five confirmed partial responses. The median PFS was 5.5 months (95% CI, 3.4 to 9.5 months), and the median OS was 19.1 months (95% CI, 9.6 months to NR). Forty percent of patients experienced a grade 3-4 treatment-related adverse event.

Conclusion: The combination regimen of nivolumab plus ipilimumab demonstrates activity in metastatic uveal melanoma, with deep and sustained confirmed responses.

Trial registration: ClinicalTrials.gov NCT01585194.

FIG 1.

Patient disposition. Thirty-nine patients were screened for the study, and four screen failures occurred because of withdrawal of consent or failure to meet eligibility criteria. Thirty-five patients were enrolled and treated in the study; 33 patients were evaluable for response, and three patients completed treatment.

FIG 2.

Efficacy of nivolumab and ipilimumab. (A) The best percentage change from baseline in target lesions by RECIST 1.1 (n = 29). Of the 33 patients evaluable for overall responses, four did not have tumor measurements. These patients had progressive disease. (*) Less than 20% increase in target lesions but progression of nontarget lesions. (†) Less than 20% increase in target lesions but development of new lesion. (B) Treatment exposure and response duration in patients with a confirmed complete response (CR) or partial response (PR) or stable disease (SD) via RECIST 1.1 (n = 17). (C) Kaplan-Meier estimate of progression-free survival (PFS) by RECIST 1.1. For the 35 patients in the study, the median PFS was 5.5 months (95% CI, 3.4 to 9.5 months). (D) Kaplan-Meier estimate of overall survival (OS). For the 35 patients included in the study, the median OS was 19.1 months (95% CI, 9.6 months to NR), and the 1-year OS was 56% (95% CI, 38% to 71%). BOR, best overall response.

FIG 3.

Progression-free survival (PFS) in subgroups. (A) PFS for patients with extrahepatic-only sites of metastases versus liver metastases was 12.0 months versus 5.5 months (P = .0918). (B) PFS for patients with different American Joint Committee on Cancer M categories of disease was not significantly different (M1a, 5.5 months; M1b, 6.3 months; M1c, 2.1 months; P = .2860). (C) PFS in patients removed from study for toxicities versus not removed from study was not significantly different (P = .6143). (*) Post 4-month landmark date.

FIG A1.

Percentage change in tumor burden from baseline over time. AE, adverse event.