defined as the time from the date of randomization to the date of the first documented disease progression ordeath due to any cause, whichever occurred first. Other outcome measures included overall survival (OS),

objective response rate (ORR), and duration of response (DoR) as assessed by central review.

A total of 577 patients were randomized, 192 to the MEKTOVI in combination with encorafenib arm, 194 tothe encorafenib arm, and 191 to the vemurafenib arm. Of the 383 patients randomized to either the

MEKTOVI in combination with encorafenib or the vemurafenib arms, the median age was 56 years (20 to89 years), 59% were male, 91% were White, and 72% had baseline ECOG performance status of 0. Ninety-

five percent (95%) had metastatic disease, 65% were Stage IVM1c, and 4% received prior CTLA-4, PD-1,or PD-L1 directed antibodies. Twenty-eight percent (28%) had elevated baseline serum lactate

dehydrogenase (LDH), 45% had ≥ 3 organs with tumor involvement at baseline, and 3% had brainmetastases. Based on centralized testing, 100% of patients’ tumors tested positive for BRAF mutations;

BRAF V600E (88%), BRAF V600K (11%), or both (< 1%).

MEKTOVI in combination with encorafenib demonstrated a statistically significant improvement in PFScompared to vemurafenib. Efficacy results are summarized in Table 5 and Figure 1. 

Table 5: Efficacy Results for COLUMBUS

MEKTOVI

with encorafenib

N=192

Vemurafenib

N=191

Progression-Free Survival

Number of events (%) 98 (51) 106 (55)

Progressive disease 88 (46) 104 (54)

Death 10 (5) 2 (1)

Median PFS, months (95% CI) 14.9 (11, 18.5) 7.3 (5.6, 8.2)

HR (95% CI)a 0.54 (0.41, 0.71)

P valueb < 0.0001

Overall Response Rate

ORR (95% CI) 63% (56%, 70%) 40% (33%, 48%)

 CR 8% 6%

PR 55% 35%

Duration of Response

Median DoR, months (95% CI) 16.6 (12.2, 20.4) 12.3 (6.9, 16.9)

CI = Confidence interval; CR = Complete response; DoR = Duration of response; HR = Hazard ratio; NE = Not estimable; ORR = Overallresponse rate; PFS = Progression-free survival; PR = Partial response. a Estimated with Cox proportional hazard model adjusted by the following stratification factors: American Joint Committee on Cancer (AJCC)

Stage (IIIB, IIIC, IVM1a or IVM1b, versus IVM1c) and Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1). b Log-rank test adjusted by the same stratification factors.

Figure 1: Kaplan-Meier Curves for Progression-Free Survival in COLUMBUS

OS was not mature at the time of analysis of PFS. 

 

16 HOW SUPPLIED/STORAGE AND HANDLING

MEKTOVI (binimetinib) is supplied as 15 mg yellow/dark yellow, unscored biconvex oval film-coatedtablets debossed with a stylized “A” on one side and “15” on the other side, available in bottles of 180

tablets (NDC 70255-010-02).

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see

USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

 

Inform patients of the following:

Cardiomyopathy