FDA Okays CDx for Encorafenib Plus Binimetinib in BRAF V600E-Mutated NSCLC

• The FDA approved the combination of encorafenib (Braftovi) plus binimetinib (Mektovi) on October 11, 2023.

• The regulatory decision is supported by findings from the phase 2 PHAROS trial (NCT03915951).

• These companion diagnostic (CDx) approvals mark the first simultaneous approval of both tests as companion diagnostics for the same therapy.

The FDA has granted approval to FoundationOne® CDx and FoundationOne Liquid CDx for use as companion diagnostics to aid in the identification of patients with metastatic non-small cell lung cancer (NSCLC) that harbors a BRAF V600E mutation, and who may benefit from treatment with the combination of encorafenib plus binimetinib.¹

This regulatory decision quickly follows the FDA approval of the combination of encorafenib plus binimetinib on October 11, 2023, for the treatment of adult patients with metastatic NSCLC harboring a BRAF V600E mutation, as detected by an FDA-approved test.²

“Foundation Medicine’s FDA-approved companion diagnostic tests offer physicians a high-quality diagnostic tool to support their personalized treatment planning,” said Mia Levy, MD, PhD, chief medical officer of Foundation Medicine, in a press release.¹ “We are thrilled to see both tests approved simultaneously for the same indication, which will expand access to this therapy option to more NSCLC patients who harbor a BRAF V600E mutation.”

Holographic concept of lung cancer display, lung disease: © catalin - stock.adobe.com

FoundationOne CDx uses tumor tissue samples and tests over 300 cancer-related genes for genomic alterations, and the FoundationOne Liquid CDx utilizes a blood sample to analyze more than 300 cancer-related genes.

Encorafenib combined with binimetinib was recently approved based on data from the phase 2 PHAROS trial. The open-label, multicenter, single-arm study enrolled patients with histologically confirmed metastatic NSCLC harboring a BRAF V600E mutation and measurable disease by RECIST v1.1 criteria.³

Enrollment was open to patients who were treatment naïve or previously treated with either first-line platinum-based chemotherapy or a first-line anti-PD-1/PD-L1 inhibitor alone or with platinum-based chemotherapy. Patients also must have had an ECOG performance status of 0 or 1 and adequate bone marrow, hepatic, and renal function.

Once enrolled, patients were given 450 mg of encorafenib orally once per day in addition to 45 mg of oral binimetinib 2 times per day. Treatment continued until progressive disease or unacceptable toxicity. The study assessed overall response rate (ORR) by RECIST v1.1 as the primary end point, and the secondary end points were duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety.

In the study, 59 treatment-naïve patients were given the combination and elicited an ORR of 75% (95% CI, 62%-85%) per RECIST v1.1 criteria.² The complete response (CR) and partial response (PR) rates were 15% and 59%, respectively.

The median DOR had not yet been reached (95% CI, 23.1-not evaluable [NE]). In the study, 75% of patients achieved a DOR of at least 6 months and 59% had a DOR of at least 12 months. Patients who were previously treated (n = 39) had an ORR of 46% (95% CI, 30%-63%). This included a CR rate of 10% and a PR rate of 36%. The median DOR was 16.7 months (95% CI, 7.4-NE), and the 6- and 12-month DOR rates were 67% and 33%, respectively.

For safety, the most common adverse events seen in at least 25% of patients were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.²

“We are grateful to see continued efforts to develop more treatment options for patients facing a NSCLC diagnosis” said Danielle Hicks, chief patient officer at GO2 for Lung Cancer, in a press release.¹ “It’s especially exciting to see that patients can be matched to this combination therapy from either a blood or tissue-based test, which expands avenues for more access to this treatment option.”

REFERENCES

1. FDA approves FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostics for Pfizer’s Braftovi (encorafenib) in combination with Mektovi (binimetinib) to identify patients with BRAF V600E alterations in metastatic NSCLC. News release. Foundation Medicine. October 12, 2023. Accessed October 13, 2023. https://tinyurl.com/shxknuyv

2. FDA approves encorafenib with binimetinib for metastatic non-small cell lung cancer with a BRAF V600E mutation. FDA. October 11, 2023. Accessed October 13, 2023. https://tinyurl.com/4jbntczm

3. An open-label study of encorafenib + binimetinib in patients with BRAFV600-mutant non-small cell lung cancer. ClinicalTrials.gov. Updated July 12, 2023. Accessed October 13, 2023. https://www.clinicaltrials.gov/study/NCT03915951#study-plan