Tepmetko (tepotinib)

P1, N=16, Recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=1000, Recruiting, Oslo University Hospital HF | N=6000 --> 1000

The patients received tepotinib through ad hoc off-label requests, with a daily dosage of 450 mg after progression following radiotherapy-based first-line treatment, with or without temozolomide. These findings support the potential of tepotinib as a targeted therapy for MET-altered glioblastoma, consistent with preclinical evidence and previous case reports. Further research is warranted to better understand the efficacy and safety of MET inhibition in this patient population.

FAXDC2 acts as a tumor suppressor in HCC, and its knockdown promotes cell proliferation, migration, invasion, and EMT via upregulating c-Met expression and enhancing its phosphorylation in HepG2 cells. Therefore, the FAXDC2/c-Met axis may serve as a noval potential therapeutic target for HCC intervention.

P1, N=19, Active, not recruiting, Institute of Cancer Research, United Kingdom | Recruiting --> Active, not recruiting

P=N/A, N=166, Ethics Committee of Cancer Hospital of Shandong First Medical University; Cancer Hospital of Shandong First Medical University

We experimentally validated several actionable findings, including tepotinib to target the IRAK1/4-cholesterol pathway in glioblastoma, brigatinib to target the MARK2/3-Hippo pathway in pancreatic cancer and gilteritinib to overcome MET mutation-driven drug resistance and metastasis. To facilitate exploration of our data, we provide KIRHub, a web-based tool that allows identification of existing inhibitors of wild-type and mutated kinases to guide precision oncology.

Recent innovations include antibody-drug conjugates (ADCs) such as TROP-2-targeting agents and HER3-DXd, which show promising efficacy in refractory disease. Next-generation tyrosine kinase inhibitors (TKIs), including lorlatinib, tepotinib, and glecirasib, have shown improved outcomes for patients with oncogene-driven NSCLC...Future efforts must prioritize overcoming resistance through combination strategies and ADCs, validating biomarkers using AI and ctDNA, streamlining CGP implementation, and addressing the unique needs of special populations. Bridging these biological and systemic challenges is essential for improving survival outcomes and ensuring equitable benefits for all NSCLC patients.

The incremental cost-effectiveness ratio (ICER) of Capmatinib treatment vs. Tepotinib treatment was calculated at 60,977.28 USD/QALY. Tepotinib was not cost-effective compared to Capmatinib as the second-line treatment for advanced or metastatic NSCLC patients with MET exon 14 skipping mutations in China.

The therapeutic strategy involved an immediate switch from rivaroxaban to therapeutic low-molecular-weight heparin (LMWH) and the initiation of dual targeted therapy with selpercatinib and tepotinib. Upon diagnosis of NBTE, a rapid oncologic work-up is warranted, as ongoing tumor progression is highly likely. This case questions the appropriateness of direct oral anticoagulants in patients with NBTE and active, progressive malignancy.

Notably, one patient with acquired MET amplification achieved a renewed partial response to the combination of sotorasib and tepotinib after progression on sotorasib monotherapy. Our findings support rebiopsy at progression on sotorasib. Further prospective trials are warranted to validate MET amplification as a resistance mechanism and to define optimal therapeutic thresholds for combined KRAS and MET inhibition.

Although the tumour relapsed 4 months postoperatively, treatment with tepotinib resulted in a favourable response and subsequent pembrolizumab therapy achieved a durable response. This case suggests that patients with sarcomatoid carcinoma, which is generally associated with a poor prognosis, may experience improved outcomes with the use of molecular targeted therapies and immune checkpoint inhibitors.