CAPANIB Capmatinib

[Product Name] Capmatinib Tablets

[Specification] 200 mg × 56 tablets/box

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 10 L 0934/22

[Summary]

Capmatinib is a kinase inhibitor targeting MET, including mutants resulting from exon 14 skipping. MET exon 14 skipping leads to the loss of a regulatory domain within the protein, thereby reducing its negative regulation and resulting in increased downstream MET signaling. Capmatinib inhibits the growth of cancer cells driven by mutant MET variants lacking the regulatory domain encoded by exon 14; it also demonstrates anti-tumor activity in murine tumor xenograft models derived from human lung tumors harboring mutations that cause MET exon 14 skipping or MET amplification. Capmatinib inhibits MET phosphorylation triggered by hepatocyte growth factor (HGF) binding or by MET amplification, as well as MET-mediated phosphorylation of downstream signaling proteins, and the proliferation and survival of MET-dependent cancer cells.

[Indications]

Capmatinib Tablets are indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors harbor mutations leading to mesenchymal-epithelial transition (MET) exon 14 skipping.

[Dosage and Administration]

Take two tablets (400 mg) orally twice daily, with or without food. Swallow the tablets whole; do not crush or chew the tablets.

[Adverse Reactions]

The most common adverse reactions (≥ 20%) are peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

[Warnings and Precautions]

Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Permanently discontinue Capmatinib Tablets in patients diagnosed with ILD/pneumonitis.

Hepatotoxicity: Monitor liver function tests. Depending on the severity, withhold the dose, reduce the dose, or permanently discontinue Capmatinib Tablets.

Risk of Photosensitivity: May cause photosensitivity reactions. Advise patients to limit direct exposure to ultraviolet (UV) light. Embryo-Fetal Toxicity: May cause fetal harm. Patients should be advised of the potential risk to the fetus and to use effective methods of contraception.

[Safety and Efficacy]

Based on the positive results from the pivotal Phase II clinical study, GEOMETRY mono-1. This was an international, prospective, multi-cohort, non-randomized, open-label study conducted in 97 adult patients with locally advanced or metastatic NSCLC whose tumors harbored *MET* exon 14 skipping (*MET*ex14) mutations. In the study, patients received oral doses of 400 mg of capmatinib tablets twice daily.

The results, as assessed by a Blinded Independent Review Committee (BIRC) according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), demonstrated the following: (1) In treatment-naïve patients (Cohort 5b: 28 patients who had not received prior treatment), the Overall Response Rate (ORR) was 68% (95% CI: 48–84), and the median Duration of Response (DOR) was 12.6 months (95% CI: 5.5–25.3). (2) In previously treated patients (Cohort 4: 69 patients who had received prior treatment), the ORR was 41% (95% CI: 29–53), and the DOR was 9.7 months (95% CI: 5.5–13.0). (3) The most common treatment-related adverse events included peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

These results highlight the therapeutic potential of capmatinib tablets in patients with NSCLC harboring *MET* exon 14 skipping mutations. The superior ORR data observed in the treatment-naïve patient group, compared to the previously treated group, underscores the clinical relevance of early diagnostic testing and prompt treatment intervention within this highly challenging patient population.

[Contraindications]

None.

[Storage]

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Please discard any remaining, unused Capmatinib tablets 6 weeks after first opening the bottle.

How to Choose: Gometinib / Boretinib / Capmatinib / Tepotinib?

Gometinib, Boretinib, Capmatinib, and Tepotinib all belong to the class of Type Ib MET tyrosine kinase inhibitors. They are primarily used to treat non-small cell lung cancer (NSCLC) characterized by MET gene abnormalities—specifically, MET exon 14 skipping mutations. Their commonality lies in their ability to target the MET pathway; however, they differ in terms of their region of development, market approval status, clinical data, side effect profiles, pricing, and accessibility.

I. Basic Comparison of the Four Drugs

Gometinib: Developed by Haihe Biopharma (China); approved for market launch only in China.

Boretinib: Developed by Anshi Biopharma (China); approved for market launch only in China.

Capmatinib: Developed by Novartis (Switzerland); approved for market launch by the US FDA, in the EU, and in China.

Tepotinib: Developed by Merck (Germany); approved for market launch by the US FDA, in the EU, and in China.

II. Key Distinctions

1. Efficacy and Clinical Evidence

Capmatinib

One of the earliest MET inhibitors to receive global approval.

Supported by mature clinical data and demonstrates high response rates.

Also shows efficacy in patients with brain metastases.

Tepotinib

A frequently recommended drug in international clinical guidelines.

Generally well-tolerated and convenient to administer.

Widely used in elderly patients.

Gometinib

Independently developed in China.

Clinical data derived from domestic patients is highly representative of the Asian population.

Offers high cost-effectiveness.

Boretinib

Market penetration and usage are currently lower than those of the other three drugs.

2. Comparison of Side Effects (Common)

All four drugs are classified as Type Ib MET inhibitors. This signifies a high degree of precision in targeting the MET receptor; they are designed to precisely attack the specific mutation while minimizing impact on other cellular pathways, thereby reducing the incidence of side effects. Gumetini: Edema, nausea, abnormal liver function

Capmatinib: Peripheral edema, nausea, fatigue

Tepotinib: Edema (most common), diarrhea, elevated creatinine

Boreatinib: Similar to common adverse reactions associated with MET inhibitors

MET inhibitors generally tend to induce edema (swelling of the legs and face); this is a characteristic feature of this class of drugs.