Results from OCEAN II: A phase II study of encorafenib + binimetinib combination in Chinese patients with <i> BRAF ^V600E </i> mutated metastatic non-small cell lung cancer.

Abstract

8640 Background: Lung cancer is the most common cause of cancer and cancer death in China. Patients (pts) with BRAF V600E mutant metastatic non-small cell lung cancer (mNSCLC) can benefit from targeted treatments such as encorafenib + binimetinib (E+B). E+B is approved in Western countries (PHAROS: NCT03915951); however, evidence of efficacy and safety in Chinese pts is lacking. OCEAN II (NCT05195632) is the 1st study to specifically evaluate the efficacy, safety and pharmacokinetic of this targeted combination in Chinese pts with BRAF V600E mutant mNSCLC. Methods: OCEAN II is an ongoing multicenter, open-label, phase 2 (P2) study with a Safety Lead-in (SLI). Eligible pts had unresectable stage IV BRAF V600E mutant NSCLC, were treatment-naive or had received systemic therapy, excluding BRAF/MEK inhibitors. Pts received E 450 mg once daily + B 45 mg twice daily. Primary endpoints were dose-limiting toxicities (DLT) during the 1st 28 days (SLI) and confirmed objective response rate (cORR) by independent central review (ICR) (P2). Secondary endpoints (P2) were disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between June 2022 and October 2023, 63 pts were enrolled (SLI = 15, P2 = 48): median age 65 yrs (range 52–82), 49% female, 75% with ECOG score = 1. There was only 1 DLT (non-serious grade 3 lipase increased) during SLI, supporting P2 initiation. At the primary analysis cut-off date (27 May 2024), the primary endpoint was met; cORR by ICR was 59.3% (95% confidence interval [CI] 45.0–72.4) in the Efficacy set, with pre-defined statistical significance criteria met. An ad hoc analysis (cut-off 27 March 2025) was conducted when all pts had ≥12 months (mo) follow up. cORR by ICR was 61.1% (95% CI 46.9–74.1), with 6 (11%) complete and 27 (50%) partial responses, and DCR of 87.0% (95% CI 75.1–94.6). Median time to response was 1.8 mo (range 1.7–13.7), median DoR 17.5 mo (95% CI 12.9–NR), median PFS 13.8 mo (95% CI 7.5–NR) and median OS 27.9 mo (95% CI 14.7–30.0). DoR and OS are not yet mature (median follow-up for OS: 21 months). Median treatment duration was 32.3 weeks, with 7 (11%) pts receiving treatment for &gt; 2 years, and 10 (15.9%) remaining on treatment. Treatment-emergent adverse events (TEAEs) ≥ grade 3 occurred in 56% of pts. Related TEAEs in ≥25% were anemia (36%), increased aspartate aminotransferase (33%), increased alanine aminotransferase (30%), increased creatine kinase (29%), vomiting (27%), increased creatinine (25%). Nine (14%) pts discontinued any drug due to AEs. Conclusions: The data confirm the clinical benefit of E+B in Chinese pts with BRAF V600E mutant mNSCLC, a population with distinct genomic and disease characteristics. No new safety concern was identified in the Chinese population. These data can support regulatory decisions and clinical practice guidelines in China. Clinical trial information: NCT03915951 .