The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) have issued a positive opinion recommending the approval of encorafenib in combination with cetuximab and FOLFOX for the first-line treatment of adult patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC). 

The positive opinion will be submitted to the European Commission (EC) with a decision on EU marketing authorisation expected later this year. 

Eric Ducournau, Chief Executive Officer, Pierre Fabre Laboratories said: “Today’s positive CHMP opinion marks an important step towards a targeted approach for patients with BRAFV600E-mutant metastatic colorectal cancer. If approved, it would be the only approved targeted therapy in the EU for this patient population in the first-line setting. This milestone reflects Pierre Fabre Laboratories’ commitment to advancing meaningful innovation in oncology and to working in close partnership with the scientific and medical community to address areas of high unmet need.”  

The CHMP positive opinion is based on results from the Phase 3 BREAKWATER trial which assessed the efficacy and safety of encorafenib in combination with cetuximab and mFOLFOX6 in patients with previously untreated BRAFV600E-mutant mCRC, compared with oxaliplatin-based chemotherapy, with or without bevacizumab.  

The regimen of encorafenib in combination with cetuximab and mFOLFOX6 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy with or without bevacizumab (median PFS 12.8 vs. 7.1 months; hazard ratio [HR] 0.53; 95% confidence interval [CI], 0.41 to 0.68; P<0.001), and demonstrated a statistically significant improvement in the dual primary endpoint of ORR in the primary analysis set (60.9% vs. 40.0%; odds ratio 2.44; P<0.001).

A confirmed objective response was observed in 65.7% of patients (95% CI, 59.4 to 71.4) compared to 37.4% (95% CI, 31.6 to 43.7) in the chemotherapy with or without bevacizumab group in the overall population. 

In an interim analysis, the encorafenib regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy with or without bevacizumab (median, 30.3 vs. 15.1 months; HR 0.49; 95% CI, 0.38 to 0.63; P<0.001), reducing the risk of death by 51%.1,2

The most frequent treatment-related adverse events (TRAEs) in the encorafenib in combination with cetuximab and mFOLFOX6 group were nausea (53.9%), anemia (46.1%), diarrhea (41.8%), decreased appetite (37.5%), vomiting (36.2%), decreased neutrophil count (34.1%), arthralgia (31.5%), and rash (30.2%). 

TRAEs of grade 3 or 4 occurred in 81.5%, and grade 5 in 4.3%. Safety profiles were consistent with those known for each agent. 

In February 2026, Pfizer Inc. received full approval from the U.S. FDA for encorafenib in combination with cetuximab and fluorouracil-based chemotherapy, for the treatment of adult patients with mCRC with a BRAFV600E mutation, as detected by an FDA authorised test.   

Encorafenib in combination with cetuximab was approved by the EC in 2020 for the treatment of adults with BRAFV600E-mutated mCRC who had received prior systemic therapy, supported by results from the randomised, active-controlled, open-label, multi-centre Phase III BEACON CRC trial. 

Source: Pierre Fabre Laboratories