Encorafenib plus binimetinib’s efficacy, safety and pharmacokinetics are consistent between Chinese patients and the global population, according to the results of the ongoing OCEAN II phase II trial in metastatic non-small-cell lung cancer (NSCLC) with BRAFV600E mutation.
Results of the PHAROS study conducted in a predominantly White population led to the approval of encorafenib plus binimetinib for adults with advanced/metastatic NSCLC with a BRAFV600E mutation in Europe and in the US. However, the epidemiology of lung cancer in China differs from Caucasian populations, with differences observed in affected age groups, rates of exposure to pollutants including tobacco, and prevalence of BRAF mutations, including BRAFV600E. [Chin J Cancer 2011;30:287-292; Front Oncol 2020;10:603]
“Consequently, similarity between Eastern and Western populations in the efficacy and safety profiles of antitumour drugs cannot be assumed,” wrote the investigators of the OCEAN II trial, explaining the need for a trial in Chinese NSCLC patients with BRAFV600E mutation. [Lung Cancer 2026;220:109580]
A total of 63 Chinese patients (median age, 65 years; male, 51 percent) with treatment-naïve or previously treated metastatic unresectable stage IV BRAFV600E-mutant NSCLC were enrolled into the ongoing multicenter, single-arm, phase II OCEAN II study. “Due to the rarity of the BRAF mutation in NSCLC, an adequately powered randomized and comparative clinical trial was deemed not feasible,” stated the investigators.
Participants received oral encorafenib 450 mg QD and oral binimetinib 45 mg BID. At a median treatment duration of 32.3 weeks, the confirmed objective response rate by independent central review (ICR) was 61 percent, of which 11 percent were complete responses and 50 percent were partial responses. Disease control rate by ICR was 87 percent. The median time to response was 1.8 months, while the median duration of response was 17.5 months. Median time to progression was 19.3 months.
Treatment-emergent adverse events (TEAEs) considered related to study treatment were reported in 98.4 percent of patients. Among them, 33.3 percent had grade 3 and 7.9 percent experienced grade 4 events. Anaemia (36.5 percent), increased aspartate aminotransaminase level (33.3 percent), increased alanine aminotransaminase level (30.2 percent), increased blood creatine phosphokinase level (28.6 percent), vomiting (27.0 percent), increased blood creatinine level (25.4 percent), hypoalbuminaemia (23.8 percent), and nausea (22.2 percent) were among the most common TEAEs. The high rate of abnormal laboratory results reported as TEAEs was similar to that reported in other clinical trials conducted in China. [Adv Ther 2025;42:1892-1906; Lancet Oncol 2023;24:1181-1195]
“The incidence of all-cause pyrexia was 27.0 percent, similar to the incidence of 22.0 percent in the PHAROS trial,” highlighted the investigators. “Three cases of pyrexia required dose interruption and one required dose reduction.”
TEAEs leading to discontinuation of all study drugs occurred in 12.7 percent of patients, while TEAEs leading to interruption of any drug were reported in 46.0 percent of patients, and dose reductions of any drug were required in 33.3 percent of patients.
After oral administration, both encorafenib and binimetinib were rapidly absorbed, reaching maximum plasma concentrations between approximately 1.5 and 2 hours. Overall, the investigators assessed the pharmacokinetic profiles of encorafenib and binimetinib in Chinese participants to be consistent with those observed in other populations.
“In conclusion, considering its efficacy and well-known safety profile, encorafenib plus binimetinib represents an additional treatment option for Chinese patients with metastatic NSCLC harbouring BRAFV600E mutation,” wrote the investigators.