Overview
11 DESCRIPTION AVMAPKI FAKZYNJA CO-PACK contains AVMAPKI (avutometinib) capsules co-packaged with FAKZYNJA (defactinib) tablets. AVMAPKI capsules contain avutometinib, a kinase inhibitor. The chemical name of avutometinib is N-(3-Fluoro-4-{[4-methyl-7-(2-pyrimidinyloxy)-2H-chromen-2-on-3-yl]methyl}-2-pyridyl)-N'-methylsulfamide potassium salt.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Avutometinib Avutometinib is a MEK1 inhibitor. Avutometinib induces the formation of inactive RAF/MEK complexes and prevents phosphorylation of MEK1/2 by RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway. Avutometinib inhibited MEK1/2 and ERK1/2 phosphorylation and proliferation of tumor cell lines harboring KRAS mutations. Treatment of cancer cells with avutometinib increased the level of phosphorylated focal adhesion kinase (FAK). Defactinib Defactinib is an inhibitor of FAK and proline-rich tyrosine kinase-2 (Pyk2), the two members of the FAK family of nonreceptor tyrosine kinases. Defactinib inhibited FAK autophosphorylation in cancer cells in vitro and in mouse xenograft models.
Indications
- 1 INDICATIONS AND USAGE AVMAPKI FAKZYNJA CO-PACK is indicated for the treatment of adult patients with KRAS -mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Common Doses
- 3.2 mg
- 200 mg
- 0.8 mg
- 2.4 mg
Dosage
2 DOSAGE AND ADMINISTRATION AVMAPKI 3.2 mg administered orally twice weekly (Day 1 and Day 4) for the first 3 weeks of each 4-week cycle. ( 2.3 ) FAKZYNJA 200 mg administered orally twice daily for the first 3 weeks of each 4-week cycle. ( 2.3 ) 2.1 Patient Selection Select patients for the treatment of recurrent LGSOC with AVMAPKI FAKZYNJA CO-PACK based on the presence of a KRAS mutation in tumor specimens [see Clinical Studies (14) ] . An FDA-approved test for the detection of a KRAS mutation in LGSOC for selecting patients for treatment with AVMAPKI FAKZYNJA CO-PACK is not available. 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Ocular Toxicities [see Warnings and Precautions (5.1) ] Serious Skin Toxicities [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] Rhabdomyolysis [see Warnings and Precautions (5.4) ] The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine...
Interactions
- 7 DRUG INTERACTIONS Strong and moderate CYP3A4 inhibitors : Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK. ( 7.1 ) Strong and moderate CYP3A4 inducers : Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK. ( 7.1 ) Warfarin : Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with warfarin and use an alternative to warfarin. ( 7.2 ) Gastric acid reducing agents : Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with proton pump inhibitors (PPIs) or H2 receptor antagonists.