General Information

Braftovi (encorafenib) is an oral small molecule BRAF kinase inhibitor. Mektovi (binimetinib) is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK).

Braftovi + Mektovi is specifically indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.

Braftovi is supplied as a capsule for oral administration. Mektovi is supplied as a tablet for oral administration. The recommended dosage of Braftovi is 450 mg orally taken once daily in combination with binimetinib until disease progression or unacceptable toxicity. Braftovi may be taken with or without food. Do not take a missed dose of Braftovi within 12 hours of the next dose of Braftovi. Do not take an additional dose if vomiting occurs after Braftovi administration but continue with the next scheduled dose. The recommended dosage of Mektovi is 45 mg orally taken twice daily, approximately 12 hours apart, in combination with encorafenib until disease progression or unacceptable toxicity. Mektovi may be taken with or without food. Do not take a missed dose of Mektovi within 6 hours of the next dose of Mektovi. Do not take an additional dose if vomiting occurs after Mektovi administration but continue with the next scheduled dose.

Clinical Trial Results

The FDA approval of Braftovi and Mektovi was based on a randomized, active-controlled, open-label, multicenter trial (COLUMBUS). Patients were required to have BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. Patients were permitted to have received immunotherapy in the adjuvant setting and one prior line of immunotherapy for unresectable locally advanced or metastatic disease. Prior use of BRAF inhibitors or MEK inhibitors was prohibited. Patients were randomized (1:1:1) to receive Braftovi 450 mg once daily in combination with binimetinib 45 mg twice daily, Braftovi 300 mg once daily, or vemurafenib 960 mg twice daily. Treatment continued until disease progression or unacceptable toxicity. Only the results of the approved dosing (Braftovi 450 mg in combination with binimetinib 45 mg) are described below. The major efficacy outcome measure was progression-free survival (PFS) of Braftovi in combination with binimetinib compared with vemurafenib as assessed by a blinded independent central review. Braftovi in combination with binimetinib demonstrated a statistically significant improvement in PFS compared to vemurafenib (14.9 vs. 7.3 months). In addition, patients in the combination therapy arm demonstrated superior overall response rate (63% vs. 40%), a longer duration of response (51 weeks vs. 31 weeks) and received a higher median dose intensity (100% vs. 99.6%) compared with the vemurafenib arm.