DOI: 10.1200/jco-26-00528 ISSN: 0732-183X

COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in BRAF V600–Mutant Advanced Melanoma

Antoni Ribas, Caroline Robert, Dirk Schadendorf, Georgina V. Long, Hussein Tawbi, Keith Flaherty, Paolo A. Ascierto, Paul Nathan, Piotr Rutkowski, Oleg V. Leonov, Paul Lorigan, Sorilla Prey, Maristella Saponara, Ana Arance, Caroline Gaudy-Marqueste, Daniil Stroyakovskiy, Celeste Lebbe, Michele Maio, Michele Del Vecchio, Pamela Salman Boghikian, Ralf Gutzmer, Roberta Depenni, Marina Miskic, Mark Russo, Reinhard Dummer

The COMBI-I trial (ClinicalTrials.gov identifier: NCT02967692 ) evaluating spartalizumab plus dabrafenib and trametinib (sparta-DabTram, n = 267) versus placebo plus dabrafenib and trametinib (placebo-DabTram, n = 265) for BRAF V600–mutant unresectable or metastatic melanoma failed to reach its primary end point of progression-free survival at 24 months. This final analysis reports overall survival (OS) during at least 5 years of extended follow-up. At the end of the trial (August 21, 2024), the median duration of follow-up was 76.9 months (range, 73.7-83.3 months). The median OS was 61.5 months (95% CI, 41.6 to not evaluable) for the sparta-DabTram arm and 41.6 months (95% CI, 30.6 to 56.9) for the placebo-DabTram arm (hazard ratio, 0.760 [95% CI, 0.598 to 0.966]). The safety findings were consistent with the known safety profile for sparta-DabTram. The most common treatment-related adverse event (TRAE) was pyrexia (65.9% v 46.2%, respectively, in the two study arms). Grade ≥3 TRAEs were reported in 57.3% and 36.7% of patients in the two arms, respectively. The combination of sparta-DabTram appears to improve OS compared with dabrafenib and trametinib alone in patients with BRAF V600–mutant metastatic melanoma.

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