Dr. Schadendorf on Expected Toxicities With Encorafenib/Binimetinib/Pembrolizumab in BRAF V600E/K-Mutated Melanoma

Dirk Schadendorf, MD, director, Department of Dermatology, West German Cancer Center, University Hospital Essen, Essen, Germany, discusses expected toxicities with the combination of encorafenib (Braftovi), binimetinib (Mektovi), and pembrolizumab (Keytruda) in BRAF V600E/K-mutated melanoma.

Data from the phase 3 IMspire150 trial (NCT02908672) and the phase 2 KEYNOTE-022 trial (NCT02130466) offer insight into potential safety signals with triplet regimens, Schadendorf explains. Additionally, the results of the phase 1/2 IMMU-TARGET trial (NCT02902042) demonstrated that encorafenib/binimetinib/pembrolizumab have overlapping efficacy and toxicity in patients with BRAF V600-mutant melanoma.

The ongoing phase 3 STARBOARD trial (NCT04657991) is evaluating the triplet combination of encorafenib, binimetinib, and pembrolizumab vs pembrolizumab plus placebo as a first-line treatment for patients with metastatic or unresectable locally advanced BRAF V600E/K-mutated melanoma.

Regarding expected toxicities that could be seen in the STARBOARD study, pembrolizumab is the current standard of care for this patient population, so it is unlikely that unexpected safety signals will arise in the control arm, Schadendorf says.

Findings from the IMMU-TARGET trial showed that encorafenib/binimetinib/pembrolizumab was associated with increased inflammatory signals, including pyrexia; however, it is difficult to determine what agent within the combination generates the increase, Schadendorf explains. Notably, because the pyrexia was found to be manageable in this patient population, it is likely that patients will be able to tolerate the triplet therapy, Schadendorf concludes.