European Commission Approves Encorafenib and Binimetinib Combination for BRAF V600E-Mutant NSCLC
Key Insights
The European Commission has approved encorafenib (BRAFTOVI) in combination with binimetinib (MEKTOVI) for treating adult patients with advanced non-small cell lung cancer (search) (NSCLC (search)) harboring a BRAFV600E (search) mutation.
The approval is based on the Phase II PHAROS trial, which demonstrated a 75% objective response rate in treatment-naive patients and 46% in previously treated patients.
Updated results from the PHAROS trial showed that 64% of treatment-naive patients maintained a response for at least 12 months, with a median duration of response of 40 months.
The European Commission (EC) has granted approval to encorafenib (BRAFTOVI) in combination with binimetinib (MEKTOVI) for the treatment of adult patients with advanced non-small cell lung cancer (search) (NSCLC (search)) whose tumors harbor a BRAFV600E (search) mutation. This decision marks a significant advancement in targeted therapy for this specific subset of lung cancer patients, offering a new treatment option where limited choices previously existed.
The approval is rooted in the findings of the Phase II PHAROS trial, a global, open-label, multicenter, non-randomized study designed to evaluate the efficacy and safety of the encorafenib and binimetinib combination in both treatment-naive and previously treated patients with BRAFV600E (search)-mutant metastatic NSCLC (search). The trial's primary endpoint was the objective response rate (ORR) as determined by independent radiology review.
PHAROS Trial Results
The PHAROS trial demonstrated clinically meaningful benefits. In treatment-naive patients (n=59), the ORR was 75% (95% CI: 62, 85), including a 15% complete response rate and a 59% partial response rate. Updated results with an additional 10-month follow-up indicated that 64% of these patients maintained a response for at least 12 months, with a median duration of response (mDOR) of 40 months (95% CI: 23.1, NE).
In patients who had received prior therapy (n=39), the ORR was 46% (95% CI: 30, 63), including 10% complete responses and 36% partial responses. Updated results showed that 44% of these patients maintained a response for at least 12 months, with a mDOR of 16.7 months (95% CI: 7.4, NE).
The safety profile of the combination was consistent with previous observations. The most common treatment-related adverse events (TRAEs) included nausea (50%), diarrhea (43%), fatigue (32%), and vomiting (29%). Treatment-related serious adverse events occurred in 14% of patients, with colitis being the most common (3%).
Clinical Significance
"We are pleased to be able to extend the treatment of BRAFTOVI® (encorafenib) in combination with MEKTOVI® (binimetinib) to adult patients with advanced NSCLC (search) with a BRAFV600E (search) mutation in Europe,” said Eric Ducournau, Chief Executive Officer of Pierre Fabre Laboratories (search). "There are currently limited targeted treatment options for BRAFV600E mutant NSCLC patients, so this approval is a significant milestone as BRAFTOVI® + MEKTOVI® will give patients the option of an additional effective targeted therapy."
About BRAF V600E-Mutant NSCLC
Lung cancer remains the leading cause of cancer-related deaths worldwide. NSCLC (search) accounts for approximately 80% of all lung cancers. BRAFV600E (search) mutations, which occur in approximately 1-2% of NSCLC cases, stimulate tumor cell growth and proliferation by altering the MAP kinase (MAPK) signaling pathway. The inhibition of both BRAF and MEK has demonstrated improved response rates compared to BRAF inhibition alone.
Regulatory and Commercial Details
Pierre Fabre Laboratories (search) holds exclusive rights to commercialize encorafenib and binimetinib in Europe and the Asia-Pacific region. Pfizer maintains exclusive rights in the United States, Canada, Latin America, Africa, and the Middle East. Ono Pharmaceutical Co., Ltd. holds rights in Japan and South Korea, and Medison has exclusive rights in Israel.