Spartalizumab Triplet Extends Overall Survival in BRAF V600–Mutant Advanced Melanoma

Clinical Summary:  

• Design/Population: COMBI-I was a phase 3, randomized, double-blind trial evaluating spartalizumab plus dabrafenib and trametinib vs placebo plus dabrafenib and trametinib in patients with unresectable or metastatic BRAF V600–mutant melanoma. 
• Key Outcomes: At a median follow-up of 76.9 months, median overall survival was 61.5 months with spartalizumab plus dabrafenib and trametinib vs 41.6 months with dabrafenib plus trametinib alone. Five-year overall survival rates were 50.1% and 42.8%, respectively. 
• Clinical Relevance: Long-term follow-up suggests that adding PD-1 inhibition to BRAF/MEK-targeted therapy may provide a durable survival advantage in BRAF V600–mutant advanced melanoma, but the finding remains hypothesis-generating because overall survival was not formally tested after the trial failed its primary progression-free survival end point. 

Final results from the phase 3 COMBI-I trial demonstrated that the addition of spartalizumab to dabrafenib and trametinib was associated with longer overall survival (OS) compared with dabrafenib plus trametinib alone in patients with BRAF V600–mutant unresectable or metastatic melanoma after more than 6 years of follow-up. 

In this double-blind trial, 532 adult patients were randomized to receive either 400 mg of intravenous spartalizumab once every 4 weeks plus 150 mg of oral dabrafenib twice daily and 2 mg of oral trametinib once daily (n = 267) or placebo plus the same dabrafenib and trametinib regimen (n = 265). The primary end point was OS during at least 5 years of extended follow-up.  

At a median follow-up of 76.9 months, median OS was 61.5 months with spartalizumab plus dabrafenib and trametinib, compared with 41.6 months with dabrafenib plus trametinib alone. Estimated 5-year OS rates were 50.1% and 42.8%, respectively. Treatment effects generally favored the spartalizumab-containing regimen across patient and tumor subgroups. 

The apparent survival benefit was accompanied by greater toxicity. Grade ≥3 treatment-related adverse events occurred in 57.3% of patients in the spartalizumab plus dabrafenib and trametinib arm and 36.7% of patients in the dabrafenib plus trametinib arm. Pyrexia was the most common treatment-related adverse event (65.9% vs 46.2%). Serious adverse events were also more frequent with the spartalizumab-containing regimen (56.2% vs 46.6%). No new safety signals emerged with extended follow-up. 

As study authors concluded, “the combination of [spartalizumab plus dabrafenib and trametinib] appears to improve OS compared with dabrafenib and trametinib alone in patients with BRAF V600–mutant metastatic melanoma.”  

Source:  

Ribas A, Robert C, Schadendorf D, et al. COMBI-I: Long-term overall survival with spartalizumab plus dabrafenib and trametinib in BRAF V600–mutant advanced melanoma. J Clin Oncol. Published online: August 12, 2026. doi: 10.1200/JCO-26-00528