Braftovi
(Encorafenib)Dosage & Administration
Take BRAFTOVI with or without food. (
BRAFTOVI may be taken with or without food
Do not take an additional dose if vomiting occurs after BRAFTOVI administration but continue with the next scheduled dose.
Braftovi Prescribing Information
Indications and Usage ( BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (mCRC)
| 12/2024 |
Dosage and Administration ( BRAF V600E orV600K Mutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a BRAF V600E orV600K mutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)] . Information on FDA-approved tests for the detection ofBRAF V600E andV600K mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a BRAF V600E mutation inplasma or tumortissue prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.2 , 14.3)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600E mutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of a BRAF V600E mutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.4) ] . If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)The recommended dosage of BRAFTOVI is 300 mg (four 75 mg capsules) orally once daily in combination with biweekly cetuximaband mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) [see Clinical Studies (14.2)] or in combination with weekly cetuximab[see Clinical Studies (14.3)] until disease progression or unacceptable toxicity. | 12/2024 |
Warnings and Precautions ( New primary malignancies, cutaneous and noncutaneous, have been observed in patients treated with BRAF inhibitors and can occur with BRAFTOVI. Cutaneous Malignancies In COLUMBUS, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6%, and basal cell carcinoma occurred in 1.6% of patients who received BRAFTOVI in combination with binimetinib. Median time to first occurrence of cuSCC/KA was 5.8 months (range 1 to 9 months) [see Adverse Reactions (6.1)] .For patients who received BRAFTOVI as a single agent, cuSCC/KA was reported in 8%, basal cell carcinoma in 1%, and a new primary melanoma in 5% of patients. In BEACON CRC, cuSCC/KA occurred in 1.4% of patients with CRC, and a new primary melanoma occurred in 1.4% of patients who received BRAFTOVI in combination with cetuximab. In PHAROS, cuSCC and skin papilloma, each occurred in 2% of patients who received BRAFTOVI in combination with binimetinib. In BREAKWATER, skin papilloma was reported in 2.6%, basal cell carcinoma in 1.3%, squamous cell carcinoma of skin in 0.9%, keratoacanthoma in 0.4% and malignant melanoma in situ in 0.4% of patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Dose modification is not recommended for new primary cutaneous malignancies. Noncutaneous Malignancies Based on its mechanism of action, BRAFTOVI may promote malignancies associated with activation of RAS through mutation or other mechanisms [see Warnings and Precautions (5.2)] . Monitor patients receiving BRAFTOVI for signs and symptoms of noncutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive noncutaneous malignancies[see Dosage and Administration (2.5)] .Hepatotoxicity can occur when BRAFTOVI is administered in combination with binimetinib. In COLUMBUS, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with binimetinib was 6% for alanine aminotransferase (ALT), 2.6% for aspartate aminotransferase (AST), and 0.5% for alkaline phosphatase. In PHAROS, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with binimetinib was 10% for AST, 9% for ALT, and 3.2% for alkaline phosphatase. In BREAKWATER, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6 was 2.2% for alkaline phosphatase, 1.3% for ALT, and 0.9% for AST. Monitor liver laboratory tests before initiation of BRAFTOVI, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage and Administration (2.3), Adverse Reactions (6.1)] .In COLUMBUS, hemorrhage occurred in 19% of patients receiving BRAFTOVI in combination with binimetinib; Grade 3 or greater hemorrhage occurred in 3.2% of patients. The most frequent hemorrhagic events were gastrointestinal, including rectal hemorrhage (4.2%), hematochezia (3.1%), and hemorrhoidal hemorrhage (1%). Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients. In BEACON CRC, hemorrhage occurred in 19% of patients receiving BRAFTOVI in combination with cetuximab; Grade 3 or higher hemorrhage occurred in 1.9% of patients, including fatal gastrointestinal hemorrhage in 0.5% of patients. The most frequent hemorrhagic events were epistaxis (6.9%), hematochezia (2.3%), and rectal hemorrhage (2.3%). In PHAROS, hemorrhage occurred in 12% of patients receiving BRAFTOVI in combination with binimetinib including fatal hemorrhage intracranial (1%); Grade 3 or 4 hemorrhage occurred in 4.1% of patients. The most frequent hemorrhagic events were anal hemorrhage and hemothorax (2% each). In BREAKWATER, hemorrhage occurred in 30% of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6; Grade 3 or 4 hemorrhage occurred in 3% of patients. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage and Administration (2.5), Adverse Reactions (6.1)] .BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients [see Clinical Pharmacology (12.2)] . In COLUMBUS, an increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients who received BRAFTOVI in combination with binimetinib. In PHAROS, an increase in QTcF to >500 ms was measured in 2.1% (2/95) of patients who received BRAFTOVI in combination with binimetinib.In BREAKWATER, an increase of QTcF >500 ms was measured in 3.6% (8/222) of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6. Monitor patients who already have or who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms [see Dosage and Administration (2.5), Adverse Reactions (6.1)] .BRAFTOVI is indicated for use as part of a regimen in combination with binimetinib, in combination with cetuximab, orin combination with cetuximab and mFOLFOX6. Refer to the prescribing information for binimetinib, cetuximab and individual product components of mFOLFOX6 for additional risk information. | 12/2024 |
BRAFTOVI is a kinase inhibitor indicated:
• in combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with aBRAF V600EorV600Kmutation, as detected by an FDA-approved test. (,1.1BRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaBRAFTOVI is indicated, in combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with a
BRAF V600EorV600Kmutation, as detected by an FDA-approved test[see Dosage and Administration (2.1)].)2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
• in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with aBRAF V600Emutation, as detected by an FDA‑approved test. (,1.2BRAF V600EMutation-Positive Metastatic Colorectal Cancer (mCRC)• BRAFTOVI is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with aBRAF V600Emutation, as detected by an FDA-approved test[see Dosage and Administration (2.1)].o This indication is approved under accelerated approval based on response rate and durability of response[see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
• BRAFTOVI is indicated, in combination with cetuximab, for the treatment of adult patients with mCRC with aBRAF V600Emutation, as detected by an FDA-approved test, after prior therapy[see Dosage and Administration (2.1)].
)2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.This indication is approved under accelerated approval based on response rate and durability of response
[see. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).]14.2BRAF V600EMutation-Positive Metastatic Colorectal Cancer (mCRC)-BRAFTOVI with Cetuximab and mFOLFOX6BRAFTOVI in combination with cetuximab and mFOLFOX6 was evaluated in a randomized, active-controlled, open-label, multicenter trial (BREAKWATER CRC; NCT04607421). Eligible patients were required to have
BRAF V600Emutation-positive metastatic colorectal cancer (CRC), as detected using the Qiagen therascreenBRAF V600ERGQ polymerase chain reaction (PCR) Kit. Other key eligibility criteria included no prior systemic treatment in the metastatic setting, absence of prior treatment with any selective BRAF inhibitor or EGFR inhibitor, tumor that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unless the patient is ineligible to receive immune checkpoint inhibitors, tumor that is not RAS-mutated or for which RAS mutation status is unknown, and Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Randomization was stratified by ECOG performance status (0 versus 1) and region (US/Canada versus Europe versus Rest of World).Patients were initially randomized 1:1:1 to one of the following treatment arms, and then 1:1 after discontinuation of enrollment of the BRAFTOVI+cetuximab arm (158 patients):
• BRAFTOVI 300 mg orally once daily in combination with cetuximab 500 mg/m2IV infusion every 2 weeks (BRAFTOVI+cetuximab arm)• BRAFTOVI 300 mg orally once daily in combination with cetuximab 500 mg/m2IV infusion every 2 weeks and mFOLFOX6 every 2 weeks (BRAFTOVI+cetuximab+mFOLFOX6 arm)• mFOLFOX6 (every 2 weeks), or FOLFOXIRI (every 2 weeks), or CAPOX (every 3 weeks), each with or without bevacizumab (administered per prescribing instructions)
mFOLFOX6 consisted of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2IV bolus, then 5-FU 2400 mg/m2continuous IV infusion over 46-48 hours; CAPOX consisted of oxaliplatin 130 mg/m2IV infusion and capecitabine 1000 mg/m2oral tablet twice daily on Days 1-14; FOLFOXIRI consisted of irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 or 3200 mg/m2(per local standard of care) continuous IV infusion over 46-48 hours.
Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, lost to follow-up, or death. Only the results of the approved regimen (BRAFTOVI in combination with cetuximab and mFOLFOX6) are described below.
The major efficacy outcome measure was confirmed objective response rate (ORR) as assessed by BICR and was evaluated in the first 110 participants randomized in each arm. An additional efficacy outcome measure included duration of response (DoR) as assessed by BICR.
A total of 236 patients were randomized to the BRAFTOVI+cetuximab+mFOLFOX6 arm and 243 to the control arm. Of these patients, the median age was 61 years, 50% were female, 60% were White, 37% were Asian, 0.4% were Multiracial, 0.2% were Black or African American, and 2.5% were not reported. Twelve percent (12%) were Hispanic or Latino, 81% were not Hispanic or Latino, and 7% were not reported. Fifty-four percent (54%) had baseline ECOG performance status of 0.
BRAFTOVI in combination with cetuximab and mFOLFOX6 demonstrated a statistically significant improvement in ORR compared to the active comparator. Efficacy results are summarized in Table 14 below.
Table 14: Efficacy Results for BREAKWATER CI = Confidence interval; CR = Complete response; DoR = Duration of response; N = Number of patients; NE = Not estimable; ORR = Objective response rate; PR = Partial response. Efficacy ParameterBRAFTOVIwith cetuximab and mFOLFOX6N=110mFOLFOX6 ± bevacizumaborFOLFOXIRI ± bevacizumaborCAPOX ± bevacizumabN=110Objective Response Rate (per BICR)ORR (95% CI)
61% (52%, 70%)
40% (31%, 49%)
CR
2.7%
1.8%
PR
58%
38%
P-valueStratified by ECOG performance status and geographic region at randomization. Cochran-Mantel-Haenszel test; tested at 1-sided alpha level of 0.001.0.0008
Duration of Response (per BICR)Median DoR, months (95% CI)
13.9 (8.5, NE)
11.1 (6.7, 12.7)
% with DoR ≥6 months
69%
34%
% with DoR ≥12 months
22%
11%
• in combination with cetuximab, for the treatment of adult patients with metastatic CRC with aBRAF V600Emutation, as detected by an FDA-approved test, after prior therapy. (,1.2BRAF V600EMutation-Positive Metastatic Colorectal Cancer (mCRC)• BRAFTOVI is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with aBRAF V600Emutation, as detected by an FDA-approved test[see Dosage and Administration (2.1)].o This indication is approved under accelerated approval based on response rate and durability of response[see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
• BRAFTOVI is indicated, in combination with cetuximab, for the treatment of adult patients with mCRC with aBRAF V600Emutation, as detected by an FDA-approved test, after prior therapy[see Dosage and Administration (2.1)].
)2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
• in combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with aBRAF V600Emutation, as detected by an FDA-approved test. (,1.3BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)BRAFTOVI is indicated, in combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a
BRAF V600Emutation, as detected by an FDA-approved test[see Dosage and Administration (2.1)].)2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC. (
BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC
In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells, which are exposed to BRAF inhibitors. Confirm evidence of
• Confirm the presence ofBRAF V600EorV600Kmutation in tumor specimens prior to the initiation of BRAFTOVI. ()2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.• The recommended dose is 450 mg orally once daily in combination with binimetinib. ()2.2 Recommended Dosage forBRAF V600EorV600KMutation-Positive Unresectable or Metastatic Melanoma and forBRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)The recommended dosage of BRAFTOVI is 450 mg (six 75 mg capsules) orally once daily in combination with binimetinib until disease progression or unacceptable toxicity. Refer to the binimetinib prescribing information for recommended binimetinib dosing information.
• Confirm the presence ofBRAF V600Emutation in plasma or tumor specimens prior to the initiation of BRAFTOVI. ()2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.• The recommended dose is 300 mg orally once daily in combination with cetuximab. ()2.3 Recommended Dosage forBRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)The recommended dosage of BRAFTOVI is 300 mg (four 75 mg capsules) orally once daily in combination with
biweeklycetuximaband mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin)[see Clinical Studies (14.2)]or in combination with weekly cetuximab[see Clinical Studies (14.3)]until disease progression or unacceptable toxicity.
• Confirm the presence ofBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI. ()2.1 Patient SelectionBRAF V600EorV600KMutation-Positive Unresectable or Metastatic MelanomaConfirm the presence of a
BRAF V600EorV600Kmutation in tumor specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-approved tests for the detection ofBRAF V600EandV600Kmutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Colorectal Cancer (CRC)Confirm the presence of a
BRAF V600Emutation inplasma ortumortissueprior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.2, 14.3)].If no mutation is detected in a plasma specimen, test tumor tissue.Information on FDA-approved tests for the detection ofBRAF V600Emutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.BRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)Confirm the presence of aBRAF V600Emutation in tumor or plasma specimens prior to initiating BRAFTOVI[see Warnings and Precautions (5.2),Clinical Studies (14.4)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection ofBRAF V600Emutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.• The recommended dose is 450 mg orally once daily in combination with binimetinib. ()2.2 Recommended Dosage forBRAF V600EorV600KMutation-Positive Unresectable or Metastatic Melanoma and forBRAF V600EMutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)The recommended dosage of BRAFTOVI is 450 mg (six 75 mg capsules) orally once daily in combination with binimetinib until disease progression or unacceptable toxicity. Refer to the binimetinib prescribing information for recommended binimetinib dosing information.
Take BRAFTOVI with or without food. (
BRAFTOVI may be taken with or without food
Do not take an additional dose if vomiting occurs after BRAFTOVI administration but continue with the next scheduled dose.
Capsules: 75 mg, hard gelatin, stylized "A" on beige cap and "LGX 75mg" on white body.
• Lactation: Advise not to breastfeed. ()8.2 LactationRisk SummaryThere are no data on the presence of encorafenib or its metabolites in human milk or the effects of encorafenib on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child from BRAFTOVI, advise women not to breastfeed during treatment with BRAFTOVI and for 2 weeks after the last dose.
• Males of Reproductive Potential: BRAFTOVI may impair fertility. ()8.3 Females and Males of Reproductive PotentialBRAFTOVI can cause fetal harm when administered to a pregnant woman
[see Use in Specific Populations (8.1)].Pregnancy TestingVerify the pregnancy status of females of reproductive potential prior to initiating BRAFTOVI
[see Use in Specific Populations (8.1)].ContraceptionFemalesAdvise females of reproductive potential to use effective contraception during treatment with BRAFTOVI and for 2 weeks after the last dose. Counsel patients to use a nonhormonal method of contraception since BRAFTOVI has the potential to render hormonal contraceptives ineffective
[see Drug Interactions (7.2)].InfertilityMalesBased on findings in male rats at doses approximately 13 times the human exposure at the 450 mg clinical dose, use of BRAFTOVI may impact fertility in males
[see Nonclinical Toxicology (13.1)].
None.