Merck Germany has announced that the European Commission (EC) has approved an expanded EU label for Erbitux (cetuximab), establishing new treatment options for patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC).
The approval, granted on June 26, 2026, allows Erbitux to be used in combination with encorafenib for patients with BRAF V600E-mutant mCRC — including as a first-line treatment alongside FOLFOX in the BREAKWATER regimen, as well as for patients who have previously received systemic therapy through the BEACON regimen.
The first-line approval is backed by results from the Phase 3 BREAKWATER trial, which demonstrated that the cetuximab–encorafenib–FOLFOX combination delivered statistically significant and clinically meaningful improvements in objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
The regimen reduced the risk of death by 51% compared with standard chemotherapy with or without bevacizumab, marking a major advance for a patient population historically associated with poor outcomes and limited treatment options.
"The approval of Erbitux in combination with encorafenib and FOLFOX marks an important milestone for patients with BRAF V600E-mutant mCRC who can now benefit from a first targeted treatment option in the first-line setting,” said Matthias Wernicke, Head of Global Therapeutic Area Specialty Care, in the healthcare business sector of Merck KGaA, Darmstadt, Germany.
“BRAF V600E-mutant mCRC is associated with a historically poor prognosis and limited effective options. This approval reinforces Erbitux as the backbone of anti-EGFR therapy in colorectal cancer — and reflects our ongoing commitment to addressing unmet needs for patients across the full treatment continuum.”
The BREAKWATER trial is a Phase 3, randomized, active-controlled, open-label, multicenter study evaluating encorafenib in combination with cetuximab and FOLFOX in previously untreated patients with BRAF V600E-mutant mCRC.
Conducted by Pfizer in collaboration with Merck KGaA, Darmstadt, Germany, and Ono Pharmaceutical, the study builds on previous regulatory milestones. The cetuximab–encorafenib–FOLFOX combination received accelerated FDA approval in December 2024 based on ORR results and achieved full FDA approval in February 2026 following positive PFS and OS data.
In the BREAKWATER trial, the targeted combination outperformed standard-of-care chemotherapy across key clinical measures.
Median PFS reached 12.8 months compared with 7.1 months for standard care, representing a 47% reduction in the risk of disease progression or death.
Overall survival was also significantly improved, with median OS of 30.3 months versus 15.1 months, translating into a 51% reduction in the risk of death and more than doubling median survival compared with standard treatment.
Confirmed ORR was 65.7% in the BREAKWATER arm compared with 37.4% in the control arm. Safety findings remained consistent with the known profiles of the individual medicines, with serious adverse events reported in 46.1% of patients receiving the combination versus 38.9% receiving standard care.
The cetuximab–encorafenib–FOLFOX regimen has also been recognized as a first-line standard of care in the April 2026 ESMO Clinical Practice Guidelines, receiving Recommendation Grade I, A for patients with metastatic colorectal cancer carrying the BRAF V600E mutation.
Beyond first-line treatment, the Phase 3 BEACON CRC trial further strengthens Erbitux’s role in later-line therapy. The EC approval also extends the use of Erbitux and encorafenib to patients with BRAF V600E-mutant mCRC who have received prior systemic therapy.
In BEACON CRC, the combination significantly improved overall survival compared with irinotecan-based control therapy, delivering median OS of 9.3 months versus 5.9 months and reducing the risk of death by 39%. The regimen maintained quality of life, with no increase in Grade ≥3 adverse events compared with standard chemotherapy.
With these approvals, Erbitux becomes the first and only anti-EGFR therapy approved for both RAS wild-type and BRAF V600E-mutant mCRC patients, supporting treatment across multiple stages of disease management.
