Nurulimab-prolgolimab superior to prolgolimab alone in metastatic melanoma

First-line nurulimab and prolgolimab combination therapy demonstrated superior efficacy compared with prolgolimab monotherapy in patients with unresectable or metastatic melanoma, according to the OCTAVA trial presented at AACR 2025.

In the iRECIST assessment, patients treated with nurulimab plus prolgolimab (median follow-up of 15.3 months) had a longer median progression-free survival (PFS; 15.4 vs 7.4 months) than those treated with prolgolimab alone (median follow-up of 15.8 months). [AACR 2025, abstract 653]

In the RECIST v.1.1 assessment, a similar PFS benefit was observed in the combination arm (median follow-up of 15.7 months) in terms of achieving a longer median PFS (6.6 vs 2.8 months) compared with the monotherapy arm (median follow-up of 17.10 months).

Moreover, nurulimab-prolgolimab recipients had higher 12-month PFS rates than prolgolimab alone recipients in both assessments (55.6 percent vs 45.9 percent [iRECIST] and 40.1 percent vs 32.1 percent [RECIST v.1.1]).

The PFS benefit observed with the combination arm vs the monotherapy arm was consistent across all subgroups, regardless of ECOG, PD-L1, and BRAF V600 mutation status, and stage of the disease, the researchers noted.

Nurulimab plus prolgolimab recipients also demonstrated a higher objective response rate (ORR; 75 percent vs 63 percent [iRECIST] and 63 percent vs 48 percent [RECIST v.1.1] than prolgolimab alone recipients.

A higher disease control rate (DCR) was also observed with the combination regimen compared with prolgolimab alone for iRECIST assessment (79.3 percent vs 61.8 percent), but a similar rate was observed for RECIST v.1.1 assessment (69.6 percent vs 70 percent).

“Overall, the fixed-dose combination of nurulimab plus prolgolimab demonstrated superior efficacy over prolgolimab monotherapy in terms of PFS, ORR, and DCR, supporting the benefit of low-dose anti-CTLA-4 in addition to anti-PD-1 therapy in the first-line treatment of patients with unresectable or metastatic melanoma,” said the researchers.

This phase III OCTAVA trial included 271 patients with unresectable or metastatic melanoma who were randomly assigned in a 1:1 ratio to receive nurulimab (1 mg/kg) plus prolgolimab (3 mg/kg) at a fixed-dose combination of 0.2 mL/kg Q3W (n=135) or prolgolimab alone (n=136) during the first four blinded infusions.

A response evaluation was conducted in 99.3 percent of patients treated with nurulimab plus prolgolimab and 91.9 percent of those treated with prolgolimab alone.

With regard to antitumour response, patients on nurulimab plus prolgolimab demonstrated a median change in tumour size of -26.5 percent compared with -10.6 percent among those on prolgolimab alone. The researchers noted that they “expect the achieved responses to deepen over time, as is typical of patients with melanoma.”

However, the overall survival (OS) data were still immature at data cut-off, with comparable OS rates between the combination and monotherapy arms (18.5 percent vs 18.4 percent).

In terms of safety, the overall incidence of adverse events (AEs) was similar between the nurulimab plus prolgolimab and prolgolimab alone arms (88.1 percent and 84.6 percent, respectively), as were the grade ≥3 (32.4 percent vs 29.6 percent) and serious (19.9 percent vs 17.8 percent) AEs.

The most common treatment-related AEs were hypothyroidism, hyperthyroidism, and increased AST or ALT levels, which were mostly mild in severity.