Capmatinib Hydrochloride

Capmaxen is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA approved test.

Capmatinib is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that reduces its negative regulation leading to increased downstream MET signaling. Capmatinib inhibited cancer cell growth driven by a mutant MET variant lacking exon 14 at clinically achievable concentrations and demonstrated anti-tumor activity in murine tumor xenograft models derived from human lung tumors with either a mutation leading to MET exon 14 skipping or MET amplification. Capmatinib inhibited the phosphorylation of MET triggered by binding of hepatocyte growth factor or by MET amplification, as well as MET mediated phosphorylation of downstream signaling proteins and proliferation and survival of MET-dependent cancer cells.

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 Capmaxen-

Strong CYP3A Inhibitors: Closely monitor patients for adverse reactions during coadministration of Capmaxen with strong CYP3A inhibitors.

Strong and Moderate CYP3A Inducers: Avoid coadministration of Capmaxen with strong and moderate CYP3A inducers.

Effect of Capmaxen on Other Drugs-

CYP1A2 Substrates: Coadministration of Capmaxen increased the exposure of a CYP1A2 substrate, which may increase the adverse reactions of these substrates.

P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates: Coadministration of Capmaxen increased the exposure of a P-gp substrate and a BCRP substrate, which may increase the adverse reactions of these substrates.

MATE1 and MATE2K Substrates: Coadministration of Capmaxen may increase the exposure of MATE1 and MATE2K substrates, which may increase the adverse reactions of these substrates.

Lung or breathing problems

Liver problems.

Pancreas problems.

• Swelling of your hands or feet
• Nausea
• Muscle or bone pain
• Tiredness and weakness
• Vomiting
• Trouble breathing
• Cough
• Loss of appetite
• Changes in certain blood tests

Pregnancy: Capmatinib can cause fetal harm when administered to a pregnant woman. There are no available data on Capmatinib use in pregnant women. Advise pregnant women of the potential risk to a fetus. Lactation: Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Capmatinib and for 1 week after the last dose. Females and Males of Reproductive Potential: Based on animal data, Capmatinib can cause malformations at doses less than the human exposure based on AUC at the 400 mg twice daily clinical dose. Pregnancy Testing: Verify pregnancy status for females of reproductive potential prior to starting treatment with Capmatinib. Contraception-

Females: Advise females of reproductive potential to use effective contraception during treatment with Capmatinib and for 1 week after the last dose.

Males: Advise males with female partners of reproductive potential to use effective contraception during treatment with Capmatinib and for 1 week after the last dose.

Interstitial Lung Disease (ILD) : Immediately withhold Capmaxen in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. Hepatotoxicity : Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of Capmaxen, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue Capmaxen. Pancreatic Toxicity : Monitor amylase and lipase at baseline and regularly during treatment with Capmaxen. Based on the severity of the adverse drug reaction, temporarily withhold, dose reduce, or permanently discontinue Capmaxen. Risk of Photosensitivity : Advise patients to limit direct ultraviolet exposure during treatment with Capmaxen. Embryo-Fetal Toxicity : Based on findings from animal studies and its mechanism of action, Capmaxen can cause fetal harm when administered to a pregnant woman.

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