The following is a summary of “First-Line, Fixed-Duration Nivolumab Plus Ipilimumab Followed by Nivolumab in Clinically Diverse Patient Populations With Unresectable Stage III or IV Melanoma: CheckMate 401,” published in the August 2023 issue of Oncology by Dummer, et al.

To address the lack of comprehensive data in patient populations historically associated with unfavorable outcomes, researchers conducted the single-arm phase IIIb CheckMate 401 study. For a study, they sought to assess the safety and efficacy of a treatment regimen comprising nivolumab in combination with ipilimumab, followed by nivolumab monotherapy, in a diverse range of patients with advanced melanoma.

Patients who were treatment-naive and presented with unresectable stage III-IV melanoma were administered nivolumab at 1 mg/kg along with ipilimumab at 3 mg/kg, administered once every 3 weeks for four doses. Subsequently, nivolumab was administered at a dose of 3 mg/kg (adjusted to 240 mg following a protocol amendment) every 2 weeks for up to a maximum of 24 months. The primary endpoint was the occurrence of grade 3-5 select treatment-related adverse events (TRAEs). The secondary endpoint included overall survival (OS). The study evaluated outcomes across subgroups based on Eastern Cooperative Oncology Group performance status (ECOG PS), presence of brain metastasis, and melanoma subtype.

A total of 533 patients received at least one dose of the study drug. In the all-treated population, the incidence of grade 3-5 select TRAEs affecting systems such as gastrointestinal (16%), hepatic (15%), endocrine (11%), skin (7%), renal (2%), and pulmonary (1%) was observed. Similar incidence rates were noted across all subgroups. With a median follow-up of 21.6 months, the 24-month OS rates were 63% in the entire treated population, 44% in the subgroup with ECOG PS 2 (including cutaneous melanoma patients), 71% in the brain metastasis subgroup, 36% in the ocular/uveal melanoma subgroup, and 38% in the mucosal melanoma subgroup.

The treatment regimen of nivolumab plus ipilimumab followed by nivolumab monotherapy was well-tolerated in patients with advanced melanoma, even those with poor prognostic indicators. Efficacy results were consistent across different subgroups, including those with brain metastases. However, patients with ECOG PS 2, ocular/uveal melanoma, and/or mucosal melanoma exhibited reduced efficacy, emphasizing the ongoing necessity for innovative treatment approaches for these challenging patient populations.

Source: ascopubs.org/doi/full/10.1200/JCO.22.02199