ENCORAFENIB CAP,ORAL
Clinical Criteria Summary
Indication & Patient Population
- • Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
- • Not indicated for the treatment of wild-type BRAF melanoma
Dosing & Administration
- • 75 mg capsule
- • Encorafenib 300 mg QD plus binimetinib 45 mg BID
Inclusion Criteria
- • Locally advanced (Stage IIIB, IIIC, or IV) unresectable or metastatic BRAF V600-mutant melanoma
- • BRAF V600E or V600K mutation or both
- • Adequate organ function and baseline labs
- • At least 1 measurable lesion
- • Treatment naïve or 1 previous immunotherapy
Exclusion Criteria
- • Untreated CNS lesions
- • Uveal or mucosal melanoma
- • Positive serology for HIV
- • Active HepB or C or both
- • Leptomeningeal mets
- • Risk for retinal vein occlusion
- • History of BMT or solid organ transplant
- • Prior BRAF or MEK inhibitor therapy
- • Previous systemic chemo other than immunotherapy
- • Clinically significant CV disease
- • Uncontrolled arterial hypertension
- • Pregnancy
Safety Considerations & Monitoring
- • Boxed warnings: None
- • Contraindications: None
- • Monitor for new primary malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma, new primary melanoma)
- • Assess for hemorrhage (most frequently gastrointestinal; fatal intracranial hemorrhage in brain metastases)
- • Assess for uveitis at each visit
- • Correct hypokalemia and hypomagnesemia prior to initiation due to QT prolongation risk
- • Monitor for embryo-fetal toxicity
- • Common adverse reactions: fatigue, nausea, vomiting, abdominal pain, arthralgia
- • Discontinuation rate 5% (most common reasons: headache, hemorrhage)
Efficacy Outcomes
- • Primary endpoint: Progression-free survival (PFS) by blinded independent review committee (BIRC)
- • Secondary endpoints: PFS encorafenib vs vemurafenib; best objective response rate (ORR); disease control rate; duration of response; time to response
- • Median OS and 1, 2, and 3 year OS rates reported
- • Quality of life favored combination over vemurafenib
Clinical Guidance & Place in Therapy
- • Metastatic melanoma
- • Unresectable/metastatic BRAF V600E or K mutated melanoma in combination with binimetinib
- • Versus vemurafenib (NCCN Category 1)
- • Standard of care for first-line metastatic melanoma includes immunotherapy alone/in combination or BRAF inhibitor plus MEK inhibitor
- • Combination BRAF/MEK inhibitors show no statistically significant difference in PFS and OS based on indirect comparisons
- • Encorafenib + binimetinib is clinically thought to be better tolerated
- • Nivolumab + ipilimumab is likely the preferred 1st choice independent of BRAF mutation status if patient is a candidate for immunotherapy and does not require immediate results due to bulky disease