FDA OKs Guardant360 CDx for Encorafenib Combo in BRAF V600E+ Metastatic CRC

The FDA has granted approval to Guardant360 CDx, a companion diagnostic to help identify patients with BRAF V600E-mutant metastatic colorectal cancer who may benefit from treatment with encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy.¹

In 2024, the encorafenib triplet was granted accelerated approval from the FDA in the same indication.² Guardant360 CDx is a liquid biopsy test that enables detection of the BRAF V600E mutation and other genomic alterations through a blood draw. This comprehensive genomic profiling allows clinicians to quickly identify eligible patients, supporting timely, molecularly informed treatment decision-making.

This approval adds to its expanding portfolio of FDA-approved companion diagnostic uses and builds on prior approvals in other solid tumor indications, including non–small cell lung cancer and breast cancer.¹

“This latest approval highlights the growing impact of liquid biopsy across advanced cancer care and underscores the utility of Guardant360 CDx in enabling precision therapy selection for patients with diverse, hard-to-treat tumors including aggressive colorectal cancer,” said Helmy Eltoukhy, chairman and co-CEO of Guardant Health, in a news release.¹ “With multiple FDA-cleared companion diagnostic claims across lung and breast cancer, and now colorectal cancer, and the ability to comprehensively profile tumor genomics from a simple blood draw, Guardant360 CDx is helping clinicians match patients to the right targeted therapies faster and more effectively.”

About the BREAKWATER Trial

Approval of the encorafenib combination was based on data from the randomized, multicenter, open-label phase 3 BREAKWATER trial (NCT04607421) evaluating first-line encorafenib in combination with cetuximab with or without mFOLFOX6 chemotherapy vs standard-of-care therapy in 147 patients with metastatic colorectal cancer harboring BRAF V600E mutations.³ Guardant360 CDx was used in the BREAKWATER trial for circulating tumor DNA analysis, supporting treatment selection and resistance monitoring.

Presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, trial data showed that the encorafenib combination yielded a statistically significant and clinically meaningful improvement in overall response rate (ORR) compared with chemotherapy alone (ORR, 60.9% vs 40.0%; OR, 2.443; 95% CI, 1.403-4.253).⁴

In addition to improved response rates, additional survival data showed extended progression-free survival (PFS) for patients treated with the encorafenib combination, with a median PFS of 12.8 months compared with 7.1 months for chemotherapy alone (HR, 0.53; 95% CI, 0.41-0.68; P <.001).⁵ The combination also demonstrated a significant overall survival (OS) benefit, with a median OS of 30.3 months vs 15.1 months in the chemotherapy arm (HR, 0.49; 95% CI, 0.38-0.63; P <.001).

The latest FDA decision follows a promising readout of updated results from the BREAKWATER trial this year at the 2026 ASCO Gastrointestinal Cancers Symposium, where tumor reductions were noted in patients treated with the combination plus FOLFIRI chemotherapy.⁶

With respect to the combination’s safety profile, the most common adverse events reported with the combination included peripheral neuropathy, nausea, fatigue, rash, diarrhea, decreased appetite, vomiting, hemorrhage, abdominal pain, and pyrexia.⁶ Subsequent reports have indicated that the safety profile of the combination remained consistent with that of each agent.

REFERENCES

1. Guardant Health receives FDA approval for Guardant360® CDx as companion diagnostic for BRAFTOVI® (encorafenib) combination in patients with BRAF V600E-mutant metastatic colorectal cancer. News release. Guardant Health. January 22, 2026. Accessed January 23, 2026. https://tinyurl.com/2e2xrkd6

2. FDA grants accelerated approval to encorafenib with cetuximab and mFOLFOX6 for metastatic colorectal cancer with a BRAF V600E mutation. FDA. December 20, 2024. Accessed January 23, 2026. https://tinyurl.com/yxnzzp6s

3. A study of encorafenib plus cetuximab with or without chemotherapy in people with previously untreated metastatic colorectal cancer. ClinicalTrials.gov. Updated August 14, 2025. Accessed January 23, 2026. https://www.clinicaltrials.gov/study/NCT04607421

4. Kopetz S, Yoshino T, Van Cutsem E, et al. Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nat Med. 2025;31(3):901-908. doi:10.1038/s41591-024-03443-3

5. Elez E, Yoshino T, Shen L, et al. First-line encorafenib + cetuximab + mFOLFOX6 in BRAF V600E-mutant metastatic colorectal cancer (BREAKWATER): Progression-free survival and updated overall survival analyses. J Clin Oncol. 2025;43(suppl 17):LBA3500. doi:10.1200/JCO.2025.43.17_suppl.LBA3500

6. Combining encorafenib and cetuximab with FOLFIRI may be an effective first-line treatment for some people with advanced colorectal cancer. News release. American Society of Clinical Oncology. January 5, 2026. Accessed January 23, 2026. https://tinyurl.com/2e77vu6w