Encorafenib Combo Earns European Approval in Advanced BRAF+ NSCLC

The FDA previously approved encorafenib/binimetinib for adults with metastatic NSCLC harboring BRAF V600E mutations in October 2023.

The European Commission has approved encorafenib (Braftovi) plus binimetinib (Mektovi) as a treatment for adults with advanced BRAF V600E–mutated non–small cell lung cancer (NSCLC), according to a press release from the developer, Pierre Fabre Laboratories.¹

The regulatory decision follows a positive opinion from the Committee for Medicinal Products for Human Use recommending the regimen’s approval for this patient population in July 2024.² Supporting data for the European Commission’s approval came from the phase 2 PHAROS trial (NCT03915951) assessing encorafenib/binimetinib in patients with advanced BRAF V600E–mutant NSCLC.

As of the data cutoff of September 22, 2022, the objective response rate (ORR) across the treatment-naïve population (n = 59) was 75% (95% CI, 62%-85%), with 15% and 59% of patients achieving complete responses (CRs) and partial responses (PRs), respectively. After 10 additional months of follow-up, a sustained response for 12 months or longer occurred in 64% of patients, and data showed a median duration of response (DOR) of 40 months (95% CI, 23.1-not estimable [NE]).

Among patients who were previously treated (n = 39), treatment with encorafenib/binimetinib yielded an ORR of 46% (95% CI, 30%-63%), with CRs reported in 10% of patients and PRs occurring in 36% at the time of the primary analysis. Additionally, 44% of patients had responses lasting for a minimum of 12 months after 10 additional months of follow-up; the median DOR in this population was 16.7 months (95% CI, 7.4-NE).

Frequent treatment-related adverse effects (TRAEs) in the PHAROS trial included nausea (50%), diarrhea (43%), fatigue (32%), and vomiting (29%). Serious TRAEs affected 14% of patients, the most common of which was colitis (3%). Investigators observed one instance of grade 5 treatment-related intracranial hemorrhage.

“We are pleased to be able to extend the treatment of encorafenib in combination with binimetinib to adult patients with advanced NSCLC with a BRAF V600E mutation in Europe,” Eric Ducournau, chief executive officer at Pierre Fabre Laboratories, said in the press release.¹ “There are currently limited targeted treatment options for [patients with] BRAF V600E mutant NSCLC, so this approval is a significant milestone as [encorafenib plus binimetinib] will give patients the option of an additional effective targeted therapy.”

In the open-label, single-arm PHAROS trial, 98 patients were assigned to receive encorafenib at 450 mg once daily plus binimetinib at 45 mg twice daily. Investigators are currently conducting the PHAROS trial at 56 sites across Italy, the Netherlands, South Korea, Spain, and the United States.

The trial’s primary end point was confirmed ORR using RECIST v1.1 criteria based on independent radiology review. Secondary end points included DOR, progression-free survival, and safety.

Patients 18 years and older with histologically confirmed stage IV NSCLC harboring a BRAF V600E mutation in lung cancer tissue as determined via local laboratory assessment were eligible for enrollment on the trial.³ Other eligibility criteria included having measurable disease per RECIST v1.1 guidelines and an ECOG performance status of 0 or 1. Having adequate bone marrow function and hepatic and renal function were additional requirements for study entry.

Those with confirmed EGFR mutations, ALK fusion oncogenes, or ROS1 rearrangements were ineligible for enrollment on the trial. Patients were also unable to enroll if they had more than 1 prior line of systemic therapy in the advanced or metastatic setting, prior therapy with a BRAF inhibitor, or impaired cardiovascular function.

The FDA previously approved encorafenib/binimetinib for adults with metastatic NSCLC harboring BRAF V600E mutations in October 2023.⁴ Supporting data for the FDA approval came from the PHAROS study.

References

1. Pierre Fabre Laboratories receives European Commission approval for BRAFTOVI® (encorafenib) in combination with MEKTOVI® (binimetinib) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAFV600E mutation. News release. Pierre Fabre Laboratories. August 30, 2024. Accessed September 3, 2024. https://tinyurl.com/as6nue82
2. Pierre Fabre Laboratories receives CHMP positive opinion for BRAFTOVI® (encorafenib) in combination with MEKTOVI® (binimetinib) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAFV600E mutation. News release. Pierre Fabre Laboratories. July 26, 2024. Accessed September 3, 2024. https://tinyurl.com/6cmkvvan
3. An open-label study of encorafenib + binimetinib in patients with BRAFV600-mutant non-small cell lung cancer. ClinicalTrials.gov. Updated July 26, 2024. Accessed September 3, 2024. https://tinyurl.com/5y54jenp
4. FDA approves encorafenib with binimetinib for metastatic non-small cell lung cancer with a BRAF V600E mutation. News release. FDA. October 11, 2023. Accessed September 3, 2024. https://bit.ly/46sC1iW