FoundationOne Liquid CDx Granted New FDA Indication in mCRC

The FDA has approved the FoundationOne®Liquid CDx to be used as a companion diagnostic for encorafenib (Braftovi) in combination with cetuximab (Erbitux) to identify patients with BRAF V600E alterations in metastatic colorectal cancer (mCRC).¹

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

FoundationOne Liquid CDx is a qualitative next-generation sequencing-based in vitro diagnostic test for patients with advanced solid tumors. Using circulating cell-free DNA, the test analyzes 324 genes. The FDA has approved the diagnostic to report short variants in 311 genes.

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In 2021, the combination of encorafenib and cetuximab was approved by the FDA for adult patients with previously treated mCRC who harbor a BRAF V600E alteration. Findings from the phase 3 BEACON CRC study (NCT02928224) support this indication.

The interventional, parallel assignment, phase 3 study enrolled 702 patients who were randomized 1:1:1 to receive either a triplet combination of encorafenib. binimetinib, and cetuximab, encorafenib and cetuximab, or the control of investigators' choice of therapy.²

Findings showed that the median OS among patients given the combination of cetuximab and encorafenib was 8.4 months (95% CI, 7.5-11.0) vs 5.4 months (95% CI, 4.8-6.6) in the control arm. For the combination, the ORR was 20% (95% CI, 13%-29%) compared with 2% in the control arm. (95% CI, 0%-7%). The partial response rate was 15% with the combination vs 2% in the control arm, and the median duration of response for the experimental group was 6.1 months (range, 4.1-8.3) vs not reached in the control group (2.6 to not reached [NR]).

With the combination, the median PFS was 4.2 months (95% CI, 3.7-5.4) compared with 1.5 months for the control group (95% CI, 1.4-1.7), and progressive disease was observed in 50% of patients given the combination vs 46% of patients given the control.

Further, death was observed in 10% of patients in the control arm and 12% of patients in the experimental arm, and adverse events which occurred in 25% of patients treated with the combination of cetuximab and encorafenib included fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

This approval of FoundationOne Liquid CDx now marks the only comprehensive genomic profiling test to be FDA-approved to identify patients with BRAF V600E alterations in mCRC who may be appropriate for treatment with the combination of encorafenib and cetuximab.

“As the second leading cause of cancer-related deaths for men and women combined, colorectal cancer has had a devastating impact on so many people,” said Michael Salienza, chief executive officer at Colorectal Cancer Alliance, in a press release.¹ “We’re encouraged by the ongoing progress happening in colorectal cancer care, and believe this approval is an important milestone in delivering broader access to more treatment options.”

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 Inc. June 9, 2023. Accessed June 9, 2023. https://tinyurl.com/2p9568nx

2. Study of encorafenib + cetuximab plus or minus binimetinib vs. irinotecan/cetuximab or infusional 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI)/cetuximab with a safety lead-in of encorafenib + binimetinib + cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer (BEACON CRC). ClinicalTrials.gov. Updated May 6, 2023. Accessed June 9, 2023. https://clinicaltrials.gov/ct2/show/NCT02928224