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

HBI-8000-303

Patient / Population Intervention / Exposition Comparaison Critère de jugement

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

404patients

Schéma

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).

Critère

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

RésultatMedian 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.

Discussion et critique

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.