Braftovi + Mektovi - 2 indications

Scroll down for more information on each indication:

• for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation; approved June 2018
• for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation; approved October of 2023

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
• for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation

Dosing/Administration

Braftovi is supplied as a capsule 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.

Mektovi is supplied as a tablet for oral administration.

• 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. 

Mechanism of Action

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). 

Side Effects

Adverse effects associated with the use of Braftovi + Mektovi may include, but are not limited to, the following:

• fatigue
• nausea
• vomiting
• abdominal pain
• arthralgia

Indication 1 - unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

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.

Indication 2 - metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation

The FDA approval for NSCLC was based on data from the ongoing Phase 2 PHAROS clinical trial, an open-label, multicenter, single‑arm study examining BRAFTOVI + MEKTOVI combination therapy in both treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. The PHAROS study met its major efficacy outcome measures of objective response rate (ORR), as assessed by independent review committee (IRC), and duration of response (DOR) in both treatment groups. For treatment-naïve patients (n=59), ORR was 75% and 59% of the patients responded for at least 12 months. Median DOR was not estimable (NE) for this group at the time of data cutoff. For previously treated patients (n=39), ORR was 46% and 33% of the patients responded for at least 12 months. Median DOR was 16.7 months.