Primary analysis of HBI-8000-303: A randomized phase 3 trial of nivolumab plus HBI-8000 or placebo in advanced melanoma

HBI-8000-303

Paciente / Población Intervención / Exposición Comparación Desenlace

In patients with advanced melanoma not previously treated with anti-PD(L)-1 therapy, HBI-8000 plus nivolumab improved progression-free survival compared with placebo plus nivolumab.

N

404pacientes

Diseño

Global phase 3, randomised, double-blind, placebo-controlled trial in unresectable or metastatic non-uveal melanoma not previously treated with PD(L)-1 inhibitors, comparing oral HBI-8000 with placebo, each combined with nivolumab, stratified by tumour PD-L1 expression and serum LDH (NCT04674683).

Desenlace

Progression-free survival assessed by a blinded independent review committee.

ResultadoMedian progression-free survival 11.7 months (95% CI 7.3-21.1) with HBI-8000 plus nivolumab vs 7.4 months (95% CI 4.5-10.1) with placebo plus nivolumab; hazard ratio 0.73 (96% CI 0.56-0.95; P = 0.0141). Confirmed objective response rate 41.4% (95% CI 34.5-48.5) vs 32.3% (95% CI 25.9-39.3). Treatment-related adverse events reported as >G3 occurred in 55% vs 18%, and 14% vs 5% discontinued therapy for treatment-related adverse events of any grade.

Khushalani NI, Pereira RP, Nakakogue TD, et al. Presented at ESMO Congress 2026, abstract LBA54, 23 October. Not yet published.

Discusión y crítica

This double-blind, placebo-controlled trial shows a progression-free survival benefit from adding HBI-8000 to nivolumab, assessed by blinded independent review. Overall survival is a secondary endpoint, but the abstract reports no survival figures despite a median follow-up of 37 months. The response rate difference comes without a P value, and no results are given by PD-L1 or LDH stratum. The gain comes with clearly more toxicity: high-grade treatment-related adverse events occurred in 55% vs 18% of patients, and discontinuations were higher, so the abstract's claim of a new standard of care rests on progression-free survival alone.