FDA Approves FoundationOne LiquidCDx for Encorafenib Combo in mCRC

The FDA previously expanded the label for cetuximab plus encorafenib for treating adult patients with metastatic colorectal cancer harboring a BRAF V600E alteration through an FDA-approved test in September 2021.

The FDA has approved the FoundationOne Liquid CDx assay as a companion diagnostic for identifying patients who may be eligible to receive encorafenib (Braftovi) plus cetuximab (Erbitux) for metastatic colorectal cancer (CRC) harboring a BRAF V600E alteration, according to a press release from Foundation Medicine Inc.¹

“Companion diagnostics are high-quality, well-validated genomic tests that provide critical information to help oncologists make informed treatment decisions for their patients,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, said in the press release. “This new companion diagnostic indication for FoundationOne Liquid CDx provides oncologists with an important, non-invasive genomic testing option for patients with this difficult to treat [metastatic] condition.”

The FDA previously expanded the label for cetuximab plus encorafenib for adult patients with metastatic CRC harboring a BRAF V600E alteration through an FDA-approved test in September 2021.² Supporting data for the expanded indication came from the phase 3 BEACON CRC trial (NCT02928224), in which cetuximab plus encorafenib produced a median overall survival [OS] of 8.4 months (95% CI, 7.5-11.0) vs 5.4 months (95% CI, 4.8-6.6) with the control regimen, consisting of irinotecan plus cetuximab or leucovorin calcium, fluorouracil, and irinotecan plus cetuximab.³

“The BEACON study showed that the combination of [cetuximab] and encorafenib significantly improved [OS] in patients with metastatic [CRC] with a BRAF V600E mutation—a subtype that typically has worse outcomes compared to those without the mutation,” David Hyman, MD, chief medical officer at Loxo Oncology and Lilly Oncology, said at the time of the expanded indication.

Manufacturers designed the FoundationOne Liquid CDx assay as a next-generation sequencing diagnostic test that analyzes 324 genes via circulating cell-free DNA to report short variants in 311 genes, thereby identifying patients who may benefit from specific therapies for advanced solid tumors.

The press release advised that the assay is for prescription use only, that use of the test does not guarantee matching a patient to a treatment, and that a negative result does not always negate the possibility of an alteration. Additionally, the manufacturers stated that testing of plasma is only acceptable in the absence of tumor tissue, and that patients who test negative with other companion diagnostic mutations should be reflexed to tumor tissue testing with an FDA-approved tumor tissue test if possible.

The FDA previously approved FoundationOne Liquid CDx for identifying patients who maybenefit from mobocertinib (Exkivity) for locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations that has progressed following platinum-based chemotherapy in May 2023.⁴ The FDA also approved FoundationOne Liquid CDx for use in patients with NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitutions who may be eligible to receive treatment with FDA-approved tyrosine kinase inhibitors including erlotinib (Tarceva) and osimertinib (Tagrisso) in December 2022.⁵

References

1. U.S. Food and Drug Administration (FDA) approves FoundationOne®LiquidCDx as a companion diagnostic for Pfizer’s BRAFTOVI® (encorafenib) in combination with cetuximab to identify patients with BRAF V600E alterations in metastatic colorectal cancer. News release. Foundation Medicine. June 9, 2023. Accessed June 12, 2023. bit.ly/42ETP7M
2. FDA expands Lilly's ERBITUX® (cetuximab) label with combination of BRAFTOVI® (encorafenib) for the treatment of BRAF V600E mutation-positive metastatic colorectal cancer (CRC) after prior therapy. News release. Eli Lilly. September 28, 2021. Accessed June 12, 2023. https://bit.ly/3ied9nV
3. Tabernero J, Grothey A, Cutsem EV, et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol. 2021;39(4):273-284. doi:10.1200/JCO.20.02088
4. FoundationOne®Liquid CDx receives FDA-approval as a companion diagnostic for EXKIVITY® (mobocertinib) to identify patients with EGFR exon 20 insertion mutations in advanced non-small cell lung cancer. News release. Foundation Medicine. May 4, 2023. Accessed June 12, 2023. bit.ly/3p48NpT
5. Foundation Medicine receives FDA approval for FoundationOne®Liquid CDx as a companion diagnostic for a certain group of tyrosine kinase inhibitors for treatment of non-small cell lung cancer patients. News release. Foundation Medicine. December 21, 2022. Accessed June 12, 2023 bit.ly/3jpU6uE