Bemcentinib plus SOC including dabrafenib is well tolerated but does not improve efficacy in metastatic melanoma

Patients with metastatic melanoma treated with standard of care (SOC) therapy (pembrolizumab The addition of bemcentinib (BGB324) to tramatinib was well tolerated; however, it did not result in an improvement in overall response rate (ORR), progression-free survival (PFS), or overall survival (OS) compared with SOC alone, according to data from the Phase 1b/2 BGBIL006 trial (NCT02872259).

In terms of safety,98% of patients (n=64) who received bemcentinib-based combination therapy experienced adverse events (AEs) of any grade, compared to 100% of patients who receivedSOC alone (n=27). The incidence of grade 3 or higher adverse events was 35% and 22%, respectively. Of note, 24% (n=18/73) of grade 3 or higher AEs were considered potentially related to bemcentinib, with the most common any-grade AEs potentially related to bemcentinib including rash, diarrhea, fatigue, and elevated transaminases. No significant differences in response or survival were observed in efficacy populations or biomarker-defined subgroups between standard treatment and combination with bemcentinib.

AXL receptors are expressed on stromal cells, myeloid cells, and tumor cells and play roles in development, epithelial-to-mesenchymal transition, and immune regulation. Bemcentinib is a first-in-class, oral, highly selective AXL inhibitor. The Phase 1b/2 study is designed to evaluate bemcentinib in combination with SOC therapy. BGBIL006 enrolled patients with previously untreated stage IIIC to IV unresectable melanoma who had an ECOG performance status of 0 to 2 and evaluable disease according to RECIST v1.1 criteria. Part 1 (dose-escalation part) of the study evaluated bemcentinib 100 mg in combination with dabrafenib/tramatinib in patients with BRAF-mutant disease and high tumor burden.

The endpoints of the study include safety, efficacy (includingORR, PFS and OS), pharmacokinetics/pharmacodynamics and biomarker analysis. The majority of patients receiving bemcentinib-based regimens (63%) and SOC alone (67%) were male. More than half (53%) of those in the bemcentinib group were older than 61 years, compared with 41% of those in the SOC group. Most patients in the bemcentinib group (65%) and SOC group (60%) had BRAF mutations. In the bemcentinib arm, 40% of patients had stage III/M1a+b disease and 60% had M1c+d disease; in the SOC arm, these rates were 62% and 38%, respectively (P=0.063).