Capmatinib is indicated for the treatment of adult patients with metastatic Non-small cell lung cancer (NSCLC) whose tumors harbor a mesenchymal-epithelial transition (MET) exon 14 skipping mutation. This mutation must be identified using a validated or FDA-approved diagnostic test before initiating treatment.

Capmatinib is a kinase inhibitor that specifically targets the MET receptor tyrosine kinase, including mutant forms produced by MET exon 14 skipping mutations. The MET exon 14 skipping alteration results in the loss of an important regulatory domain in the MET protein, which normally helps control its activity. Without this regulatory region, MET signaling becomes excessively active, leading to increased tumor cell growth and survival. Capmatinib inhibits the abnormal activation of MET signaling pathways by blocking MET phosphorylation that occurs after binding with hepatocyte growth factor (HGF) or due to MET gene amplification. By suppressing MET activity, Capmatinib interferes with downstream signaling proteins responsible for cancer cell proliferation and survival. At clinically achievable concentrations, Capmatinib has been shown to inhibit the growth of cancer cells driven by MET exon 14 skipping mutations. Preclinical studies also demonstrated significant antitumor activity in mouse xenograft models derived from human lung tumors harboring MET exon 14 skipping mutations or MET amplification.

Patient Selection: Select patients for treatment with Capmatinib based on the presence of a mutation that leads to MET exon 14 skipping in tumor or plasma specimens. If a mutation that leads to MET exon 14 skipping is not detected in a plasma specimen, test tumor tissue if feasible.

Recommended Dose: The recommended dosage of Capmatinib is 400 mg orally twice daily with or without food. Swallow Capmatinib tablets whole. Do not break, crush or chew the tablets. If a patient misses or vomits a dose, instruct the patient not to make up the dose, but to take the next dose at its scheduled time.

Effect of Other Drugs on Capmatinib

• Strong CYP3A inhibitors: Concomitant use with strong CYP3A inhibitors may increase Capmatinib exposure and raise the risk of adverse reactions. Patients receiving such combinations should be monitored closely.
• Strong or moderate CYP3A inducers: Co-administration with strong or moderate CYP3A inducers should be avoided because they may reduce Capmatinib plasma concentrations and decrease its effectiveness.

Effect of Capmatinib on Other Drugs

• CYP1A2 substrates: Capmatinib may increase the exposure of CYP1A2 substrate drugs, which can lead to increased side effects of those medications.
• P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) substrates: Co-administration may increase the levels of drugs transported by P-gp or BCRP, potentially increasing their toxicity.
• MATE1 and MATE2K substrates: Capmatinib may increase the exposure of medications that are substrates of these transporters, thereby increasing the likelihood of adverse reactions.

Common adverse reactions associated with Capmatinib include:

• Lung or breathing problems
• Liver abnormalities
• Pancreatic disorders
• Swelling of hands or feet (peripheral edema)
• Nausea and vomiting
• Muscle or bone pain
• Fatigue and weakness
• Difficulty breathing and cough
• Loss of appetite
• Abnormal laboratory test results

Pregnancy: Capmatinib may cause fetal harm when administered during pregnancy. There are currently no adequate clinical data regarding its use in pregnant women. Women should be informed about the potential risk to the developing fetus.

Lactation: Because of the potential risk of serious adverse reactions in breastfed infants, women should avoid breastfeeding during treatment with Capmatinib and for at least 1 week after the final dose.

Reproductive Potential: Based on animal studies, Capmatinib may cause fetal malformations even at exposure levels lower than those used in humans. Pregnancy testing should be performed in women of reproductive potential before starting treatment.

Contraception

• Females: Women of reproductive potential should use effective contraception during treatment and for 1 week after the last dose.
• Males: Male patients with female partners of reproductive potential should also use effective contraception during treatment and for 1 week after the final dose.

Interstitial Lung Disease (ILD): If ILD or pneumonitis is suspected, Capmatinib should be withheld immediately and permanently discontinued if confirmed.

Hepatotoxicity: Liver function tests (ALT, AST, bilirubin) should be monitored before treatment, every two weeks during the first three months, and periodically thereafter.

Pancreatic toxicity: Amylase and lipase levels should be monitored before and during therapy.

Photosensitivity: Patients should avoid excessive sunlight and ultraviolet exposure during treatment.

Embryo-fetal toxicity: Capmatinib may harm the fetus if used during pregnancy.

Pediatric Use: Safety and effectiveness of Capmatinib in pediatric patients have not been established.

Geriatric Use: Clinical studies showed no significant differences in safety or effectiveness between elderly and younger patients.

Renal Impairment: No dose adjustment is required for patients with mild or moderate renal impairment. However, Capmatinib has not been adequately studied in patients with severe renal impairment.

Cytotoxic Chemotherapy

Store below 25°C in a cool, dry place, protected from light. Keep out of the reach of children.