A phase 2 study of encorafenib in combination with binimetinib for Chinese participants with BRAFV600E mutated metastatic non-small cell lung cancer: Results from the OCEAN II study

Purpose The ongoing OCEAN II study (ClinicalTrials.gov identifier: NCT05195632) evaluates encorafenib in combination with binimetinib (E+B) in Chinese participants with BRAF V600E -mutated metastatic non-small cell lung cancer (NSCLC). Methods Participants with metastatic unresectable stage IV BRAF V600E -mutated NSCLC (treatment-naïve or with prior systemic therapy excluding BRAF/MEK-inhibitors), were enrolled in a phase 2 study with two parts: safety lead-in (SLI) and pivotal part (PP). Participants received daily oral encorafenib (450mg) and twice daily oral binimetinib (90mg total). Primary endpoints were dose-limiting toxicities (DLT) during SLI and confirmed objective response rate by independent central review (cORR-ICR) during PP. Secondary endpoints were other measures of efficacy, safety, and pharmacokinetics. Results In total, 63 participants were enrolled. One DLT (non-serious Grade 3 lipase increased) during SLI considered possibly related to E+B resolved without intervention, supporting initiation of PP. Pre-defined statistical efficacy criteria on the first 50 participants were met. In the main analysis, cORR-ICRwas59% (95%CI 45–72). At a later ad hoc analysis, cORR-ICR was 61% (95%CI 47–74), disease control rate 87% (95%CI 75–95). Medians (95%CI) were, time-to-response 1.8 months, duration of response 17.5 months, progression-free survival 13.8 months (7.5–not estimable), overall survival 27.9 months (14.7–30.0). 98.4% of participants experienced ≥1 treatment-related TEAE, and 55.6% had any Grade ≥3 TEAE. Nine (14.3%) participants discontinued any drug due to adverse events. Conclusion These data confirm the clinical benefit of E+B in Chinese participants with BRAF V600E -mNSCLC, a population with distinct genomic and disease characteristics. No new safety concerns were identified in Chinese participants.