Therapeutic efficacy of Encorafenib

1. Unresectable or Metastatic Melanoma with Positive BRAF V600E or V600K Mutation

The combination of encorafenib and binimetinib was evaluated in a randomized, active-controlled, open-label, multicenter trial (COLUMBUS).

Compared with vemurafenib, the combination of encorafenib and binimetinib showed a statistically significant improvement in progression-free survival (PFS). The median PFS was 14.9 months and 7.3 months, respectively, with a hazard ratio (HR) of 0.54. Overall survival (OS) was also improved: the median OS was 33.6 months and 16.9 months, respectively, with an HR of 0.67. The objective response rate (ORR) was 63%, including a complete response (CR) rate of 8% and a partial response (PR) rate of 55%. The median duration of response (DOR) was 16.6 months.

2. Metastatic Colorectal Cancer with Positive BRAF V600E Mutation – Encorafenib in Combination with Cetuximab and mFOLFOX6 Regimen

The combination of encorafenib, cetuximab, and the mFOLFOX6 regimen was evaluated in a randomized, active-controlled, open-label, multicenter trial (BREAKWATER).

Compared with the active control, the combination of encorafenib, cetuximab, and mFOLFOX6 showed a statistically significant improvement in objective response rate (ORR). The ORR was 61% and 40%, respectively. The median duration of response (DOR) was 13.9 months and 11.1 months, respectively.

3. Metastatic Colorectal Cancer with Positive BRAF V600E Mutation

The combination of encorafenib and cetuximab was evaluated in a randomized, active-controlled, open-label, multicenter trial (BEACON CRC).

Compared with the active control, the combination of encorafenib and cetuximab showed statistically significant improvements in overall survival (OS), objective response rate (ORR), and progression-free survival (PFS). The median OS was 8.4 months and 5.4 months, respectively, with a hazard ratio (HR) of 0.60. The ORR was 20% and 2%, respectively. The median PFS was 4.2 months and 1.5 months, respectively, with an HR of 0.40.

4. Metastatic Non-Small Cell Lung Cancer with Positive BRAF V600E Mutation

The combination of encorafenib and binimetinib was evaluated in an open-label, multicenter, single-arm study (PHAROS).

In treatment-naive patients, the objective response rate (ORR) was 75%, including a complete response (CR) rate of 15% and a partial response (PR) rate of 59%. In previously treated patients, the ORR was 46%, including a CR rate of 10% and a PR rate of 36%. Among treatment-naive patients who achieved a response, 64% had a duration of response (DOR) of ≥12 months, and 43% had a DOR of ≥24 months. Among previously treated patients who achieved a response, 44% had a DOR of ≥12 months, and 22% had a DOR of ≥24 months.

FDA，2025.03