FDA Approves Companion Diagnostics for Encorafenib/Binimetinib in BRAF V600E+ Metastatic NSCLC

The FDA has approved FoundationOne® CDx and FoundationOne Liquid CDx for use as companion diagnostics to identify patients with metastatic non–small cell lung cancer (NSCLC) harboring BRAF V600E mutations who may benefit from treatment with the combination of encorafenib (Braftovi) plus binimetinib (Mektovi).¹

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

On October 11, 2023, the FDA approved encorafenib plus binimetinib 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,” Mia Levy, MD, PhD, chief medical officer of Foundation Medicine, stated in a news 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.”

The FDA approval of encorafenib plus binimetinib was based on data from the phase 2 PHAROS trial (NCT03915951), where treatment-naïve patients treated with the doublet (n = 59) experienced an objective response rate (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 duration of response (DOR) had not yet been reached (95% CI, 23.1-not evaluable [NE]). Notably, 75% of patients achieved a DOR of at least 6 months and 59% had a DOR of at least 12 months.³

Furthermore, previously treated patients (n = 39) experienced an ORR of 46% (95% CI, 30%-63%), including 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.

PHAROS was an open-label, multicenter, single-arm study that enrolled patients with histologically confirmed metastatic NSCLC harboring a BRAF V600E mutation and measurable disease by RECIST v1.1 criteria.⁴ Patients needed to be treatment naïve or previously treated with either first-line platinum-based chemotherapy or a first-line anti–PD-1/PD-L1 inhibitor alone or in combination with platinum-based chemotherapy. Other key inclusion criteria included an ECOG performance status of 0 or 1 and adequate bone marrow, hepatic, and renal function.

Prior treatment with a BRAF or MEK inhibitor was not permitted. Patients who received more than 1 prior line of systemic therapy in the metastatic/advanced setting were also not allowed. The study also excluded patients with EGFR mutations, ALK fusions, or ROS1 rearrangements.

All enrolled patients received 450 mg of oral encorafenib once per day plus 45 mg of oral binimetinib twice per day, and treatment continued until progressive disease or unacceptable toxicity.

ORR by RECIST v1.1 criteria was the study’s primary end point. Secondary end points included DOR, disease control rate, progression-free survival, overall survival, and safety.

The most common adverse effects reported in at least 25% of patients included 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” Danielle Hicks, chief patient officer at GO2 for Lung Cancer, stated in a news 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://www.foundationmedicine.com/press-releases/ef74765d-a0dd-4c96-a9f6-4c6398c03be2
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://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-encorafenib-binimetinib-metastatic-non-small-cell-lung-cancer-braf-v600e-mutation
3. Encorafenib (Braftovi); Prescribing information. Pfizer Inc. Updated October 2023. Accessed October 13, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210496s014lbl.pdf
4. 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