A final analysis of the phase 3 COMBI-I trial (NCT02967692), published in the Journal of Clinical Oncology, showed that adding the anti\u2013PD-1 antibody spartalizumab to dabrafenib (Tafinlar) and trametinib (Mekinist; sparta-DabTram) was associated with longer overall survival (OS) than dabrafenib and trametinib alone in patients with BRAF V600-mutant unresectable or metastatic melanoma.<\/p>\n
At the trial\u2019s conclusion on August 21, 2024, the median duration of follow-up was 76.9 months (range, 73.7 to 83.3). A total of 127 patients (47.6%) had died in the sparta-DabTram arm compared with 151 patients (57.0%) in the placebo-DabTram arm. Median OS was 61.5 months (95% CI, 41.6 to not evaluable) with sparta-DabTram compared with 41.6 months (95% CI, 30.6-56.9) with placebo-DabTram, translating to a HR of 0.760 (95% CI, 0.598-0.966). The estimated OS rates at 60 months were 50.1% (437%-56.1%) for the sparta-DabTram arm vs 42.8% (5% CI, 36.6%-48.9%) for the placebo-DabTram arm. Treatment effect favored sparta-DabTram (HR less than 1) across most subgroups of patient and tumor characteristics that were examined.<\/p>\n
Adverse events (AEs) of any kind occurred in 99.3% of patients in the sparta-DabTram arm and 97.3% in the placebo-DabTram arm. Pyrexia was the most common AE overall and the most common treatment-related AE (TRAE), occurring in 65.9% of patients on sparta-DabTram vs 46.2% on placebo-DabTram; pyrexia also lasted longer with the triplet regimen (median 13.0 days vs 9.0 days) and tended to occur earlier. All-grade and grade 3 or higher TRAEs occurred in 98.5% and 57.3% of patients in the sparta-DabTram arm, respectively, compared with 88.6% and 36.7% of patients receiving the placebo-DabTram.<\/p>\n
Serious AEs were reported in 56.2% vs 46.6% of patients, with pyrexia being the most common (17.2% vs 6.1%). Skin reactions were the most common AEs of special interest associated with spartalizumab, affecting 61.0% of the sparta-DabTram arm vs 47.0% of the placebo-DabTram arm. Other immune-mediated AEs of special interest, including colitis, pancreatic enzyme elevations, and endocrine and liver toxicities, occurred more frequently with sparta-DabTram.<\/p>\n
The study authors identified several limitations, including a high proportion of patients censored from the OS analysis because of study termination rather than a defined event, an imbalance in post-progression use of immune checkpoint inhibitors between arms, treatment discontinuations due to grade 3 or higher AEs, and nonadherence to protocol-specified dosing that may have been influenced by the onset of pyrexia. Post-treatment antineoplastic therapy was used in 46.1% of the sparta-DabTram arm and 50.6% of the placebo-DabTram arm, with immunotherapy, most often anti\u2013PD-1 agents, used more frequently after progression in the placebo-DabTram arm (40.0%) than the sparta-DabTram arm (27.7%).<\/p>\n
COMBI-I Trial Design<\/p>\n
The randomized, double-blind, placebo-controlled trial enrolled 532 adult patients with histologically confirmed unresectable or metastatic BRAF V600-mutant cutaneous melanoma between September 13, 2017, and July 4, 2018. Patients received either intravenous spartalizumab at 400 mg every 4 week, plus oral dabrafenib at 150 mg twice daily and trametinib at 2 mg once daily (n = 267), or the same dabrafenib\/trametinib regimen with an intravenous placebo in place of spartalizumab, referred to as placebo-DabTram (n = 265).<\/p>\n
The trial\u2019s original primary end point, improved median progression-free survival (PFS) at 24 months, was not met (16.2 months vs 12 months; HR, 0.82; 95% CI, 0.66-1.03; P = .042).<\/p>\n
The study authors noted that COMBI-I had the longest reported follow-up among trials evaluating an immune checkpoint inhibitor combined with BRAF and MEK inhibitors, with a clear separation of the Kaplan-Meier survival curves emerging after 6 months and sustained over time. The safety results in this final analysis were consistent with those from the trial’s primary analysis, and no new safety signals were observed.<\/p>\n
The authors concluded that the combination of sparta-DabTram suggested a trend toward a survival benefit over dabrafenib and trametinib alone in patients with BRAF V600-mutant metastatic melanoma, though they noted that the finding stems from a trial that did not meet its formal primary end point.<\/p>\n
Reference<\/p>\n
Ribas A, Robert C, Schadendorf D, et al. COMBI-I: long-term overall survival with spartalizumab plus dabrafenib and trametinib in\u00a0BRAF\u00a0V600-mutant advanced melanoma.\u00a0J Clin Oncol. Published online August 12, 2026. doi:10.1200\/JCO-26-00528<\/p>\n","protected":false},"excerpt":{"rendered":"A final analysis of the phase 3 COMBI-I trial (NCT02967692), published in the Journal of Clinical Oncology, showed…\n","protected":false},"author":2,"featured_media":601968,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[163,85,46],"class_list":["post-601967","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-il","tag-israel"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/601967","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=601967"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/601967\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/601968"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=601967"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=601967"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=601967"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}