Results from this study suggest that this combination is active and should be considered for this patient population, though additional research is still necessary.
A single-arm phase 2 study published in the Journal of Clinical Oncology found that the combination regimen of nivolumab (Opdivo) plus ipilimumab (Yervoy) demonstrates activity in metastatic uveal melanoma, with deep and sustained confirmed responses.
Results from this study, as well as the Spanish GEM-1402 study, suggest that this combination is active and should be considered for this patient population. However, additional research is still necessary to characterize the molecular and genomic signatures of responders and nonresponders.
“These data were intended to serve as a new benchmark in uveal melanoma, and the results of the current study demonstrate improvement,” the authors wrote.
In this phase 2 study, researchers enrolled patients with metastatic uveal melanoma with any number of prior treatments. Participants received 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab for 4 cycles, followed by nivolumab maintenance therapy for up to 2 years.
The primary end point for the study was overall response rate (ORR) as determined by RECIST 1.1 criteria, and key secondary end points were progression-free survival (PFS), overall survival (OS), and adverse events (AEs).
In total, 35 patients were enrolled in the study and 33 were evaluable for efficacy. The median age at diagnosis was 62 years, and 34% of patients were male.
The median duration of follow-up was 13.0 months (range, 1.3-43.5 months). The ORR was 18%, including 1 confirmed complete response (CR) and 5 confirmed partial responses (PRs). Moreover, 11 patients (33%) had a best response of stable disease, with 6 of these individuals maintaining this response for at least 6 months.
Ultimately, 41% of evaluable patients experienced a reduction from baseline in target lesion size. In patients with a CR or PR or stable disease, the median percentage tumor change was –21.0%.
The median PFS was 5.5 months (95% CI, 3.4-9.5 months). Median OS was 19.1 months (95% CI, 9.6 months to NR), and the 1-year OS was 56% (95% CI, 38%-71%)
Regarding safety, 40% of patients experienced a grade 3 to 4 treatment-related AE. The most common AEs of any grade observed were diarrhea, abnormal liver enzymes, pruritis, and hypothyroidism. Further, 10 patients (29%) were removed from the study due to AEs. However, no treatment-related deaths occurred.
“Compared with the sentinel publication on the use of nivolumab and ipilimumab in cutaneous melanoma, there were no new safety signals detected in the uveal melanoma population,” the authors noted.
Importantly, the small number of patients included in the current study reduced the investigators ability to correlate clinical features with response. However, it is also important to note that none of the 6 responders in this study had received prior therapy in the metastatic setting.
Additionally, the small number of patients in this study also made assessment of clinical factors predictive of response difficult; however, the current analyses suggested a numeric improvement overall in PFS and OS in patients who have extrahepatic disease only.
Pelster MS, Gruschkus SK, Bassett R, et al. Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study. Journal of Clinical Oncology. doi: 10.1200/JCO.20.00605