STARBOARD Triplet Yields 33-Month Median PFS in BRAF V600–Mutant Melanoma

In an interview with CancerNetwork®, Dirk Schadendorf, MD, professor of dermatology and oncology and director of the Department of Dermatology and the West German Cancer Center at University Hospital Essen in Germany, discussed final results from the phase 3 STARBOARD trial (NCT04657991), which he presented at the 2026 European Society for Medical Oncology (ESMO) Congress. The study compared first-line encorafenib (Braftovi), binimetinib (Mektovi), and pembrolizumab (Keytruda) with placebo plus pembrolizumab in patients with unresectable locally advanced or metastatic BRAF V600–mutant melanoma.

Schadendorf explained how the study was redesigned after slowed enrollment, with 220 patients ultimately randomized and objective response rate (ORR) by blinded independent central review becoming the primary end point. The confirmed ORR was 70.0% with the triplet vs 32.7% in the control arm, and median progression-free survival (PFS) was 33.0 months vs 3.4 months (HR, 0.33; 90% CI, 0.24–0.46). Overall survival was immature but trended in favor of the triplet (HR, 0.71; 90% CI, 0.48–1.05). Grade 3 or 4 treatment-emergent adverse events occurred in 70.0% vs 39.1% of patients, respectively. He also shared where he sees the triplet fitting into first-line practice.

Transcript:

Schadendorf: STARBOARD is a trial that tries to combine both new treatments we have had in hand over the last 10 years: targeted therapy, meaning the combination of BRAF and MEK inhibition, and checkpoint blockade, a triplet therapy. We have tested triplet therapy regimens in the past in prospective clinical trials in comparison with BRAF/MEK inhibition alone. We saw only very limited clinical benefit, and there was a pressing question of whether we should also compare triplet therapy against PD-1 inhibitor monotherapy, because PD-1 monotherapy is considered the standard of care in first-line treatment in many countries.

STARBOARD compared triplet therapy with encorafenib, binimetinib, and pembrolizumab against pembrolizumab in patients with first-line BRAF V600–mutant melanoma. Initially, the study was planned as a registrational study with 600 patients. However, with the post-COVID period and the changing landscape over the 18 months of initial recruitment, from the middle of 2022 to early 2024, roughly 200 patients were included in the study. The sponsoring company, Pfizer, decided to change the design of the study and made overall response rate the primary end point, with blinded independent review required. The same was true for progression-free survival; the original primary end point of the study became the key secondary end point, also with blinded review.

We saw impressive results. The confirmed response rate was 70% for the triplet therapy, in contrast to almost 33% for checkpoint blockade. That was already a huge difference, which was statistically significant in favor of the triplet therapy. Not only that; disease control was also improved. Median PFS [progression-free survival] was 3.4 months with checkpoint blockade monotherapy vs 33 months with the triplet therapy. That is a huge difference, which was also statistically highly significant.

Because the study was closed prematurely, the survival data, which are important when we are talking about changing the landscape and changing the standard of care, were immature. Still, we saw a hazard ratio of 0.71, so a 29% reduction in the death rate in favor of the triplet therapy, which barely missed the level of statistical significance. Maybe by waiting half a year longer, or with 50 more patients, we would have seen a positive overall survival result in that clinical trial.

One has to say that the triplet therapy is obviously also a little bit more toxic. When we look at grade 3 or 4 toxicities overall, we see roughly 40% in the monotherapy arm and roughly 70% in the triplet arm. There is no doubt that we have high clinical efficacy, and now one has to discuss, even without any official registration, where the right spot is to use this triplet therapy. Easy-to-treat patients who are PD-L1 positive are probably still well served with PD-1 monotherapy or checkpoint blockade alone, but everyone else should also be considered for triplet therapy, in my view. It’s an interesting new option for treating patients in the first line, with a clear benefit across multiple end points.

Reference

Schadendorf D, Dummer R, Sullivan RJ, et al. STARBOARD phase 3: a randomized, double-blind study of first-line encorafenib, binimetinib, and pembrolizumab vs placebo and pembrolizumab for unresectable locally advanced or metastatic BRAF V600-mutant melanoma. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 2071O.