1 INDICATIONS AND USAGE
ZELBORAF® is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with ZELBORAF [see Warnings and Precautions (5.2)]. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at http://www.fda.gov/CompanionDiagnostics.
5 WARNINGS AND PRECAUTIONS
5.1 New Primary Malignancies
- Other Malignancies
Based on mechanism of action, ZELBORAF may promote malignancies associated with activation of RAS through mutation or other mechanisms [see Warnings and Precautions (5.2)]. Monitor patients receiving ZELBORAF closely for signs or symptoms of other malignancies.
5.2 Tumor Promotion in BRAF Wild-Type Melanoma
In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells that are exposed to BRAF inhibitors. Confirm evidence of BRAF V600E mutation in tumor specimens prior to initiation of ZELBORAF [see Indications and Usage (1) and Dosage and Administration (2.1)].
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
Neoplasms benign, malignant and unspecified (incl. cysts and polyps): Progression of pre-existing chronic myelomonocytic leukemia with NRAS mutation [see Warnings and Precautions (5.1)].
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Vemurafenib is an orally available inhibitor of some mutated forms of BRAF serine-threonine kinase, including BRAF V600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR at similar concentrations. Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, causing cell proliferation in the absence of growth factors normally required for proliferation. Vemurafenib demonstrated anti-tumor effects in cellular and animal models of melanomas with mutated BRAF V600E.
14 CLINICAL STUDIES
- Treatment-Naive Patients
Trial 1, an international, open-label, randomized controlled trial, equally allocated 675 patients with treatment-naive, BRAF V600E mutation-positive unresectable or metastatic melanoma, as detected by the cobas® 4800 BRAF V600 Mutation Test
- Patients Who Received Prior Systemic Therapy
In a single-arm, multicenter, multinational trial (Trial 2), 132 patients with BRAF V600E mutation-positive metastatic melanoma, as detected by the cobas® 4800 BRAF V600 Mutation Test
17 PATIENT COUNSELING INFORMATION
Evidence of BRAF V600E mutation in the tumor specimen with an FDA approved test is necessary to identify patients for whom treatment with ZELBORAF is indicated [see Dosage and Administration (2.1)].
(2022.12.16 업데이트)