Tabrecta (capmatinib) / Incyte, Novartis - LARVOL DELTA

Real world efficacy of dose-reduced capmatinib and tepotinib for advanced MET exon 14–skipping+ NSCLC. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

MET tyrosine kinase inhibitors in combination with EGFR tyrosine kinase inhibitors in NSCLC patients with EGFR mutations and acquired MET alterations: a systematic review and meta-analysis. (PubMed, BMC Cancer) - "The findings from this meta-analysis suggest that the combination of MET-TKI and EGFR-TKI represents a promising therapeutic approach for NSCLC patients who have acquired MET alterations following EGFR-TKI treatment. Notably, the combination of MET-TKI and a third-generation EGFR-TKI demonstrated enhanced survival benefits compared to the combination with a first-generation EGFR-TKI. Furthermore, different MET-TKIs based combination therapy did not display significant differences in efficacy, while capmatinib based combination therapy showed better safety profile and lower hepatotoxicity."

Clinical • Journal • Retrospective data • Review • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Topical application of Cap-loaded hydrogels inhibits corneal neovascularization. (PubMed, Exp Eye Res) - "This study aimed to examine the function of the new therapeutic agent capmatinib (Cap), a highly selective inhibitor of MET that plays an important role in angiogenesis, in treating CNV...On day 14, the Cap-Gel group showed the most significant inhibition of corneal neovascularization, with the shortest neovessel length (0.48±0.13 mm), smallest CNV area (3.77±0.78 mm2), and lowest clinical assessment score (3.33±0.52). Taken together, our results suggest that Cap-Gel could be a promising drug candidate for treating CNV."

Journal • Fibrosis • Immunology • MET

Metabolic reprogramming regulates tyrosine receptor kinase c-Met in prostate cancer (AACR 2025) - "Etomoxir (FAO inhibitor) and Atovaquone (OXPHOS inhibitor) suppressed c-Met protein expression through the mTOR-P70S6K pathway in PC cells. Rapamycin (mTOR inhibitor) reduced c-Met expression in PC3 and DU145 PC cells. Preliminary analysis suggests that the mitochondrial inhibitors and capmatinib, an FDA-approved c-Met inhibitor, have a combinatorial effect. Collectively, this study suggests that mitochondrial metabolic reprogramming to FAO in PC upregulates c-Met activity."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MET • SIRT1 • SLC2A1

Targeting the HGF/MET/TWIST1 pathway in lung adenocarcinoma brain metastases (AACR 2025) - "Finally, capmatinib or harmine treatment in mice with BM led to BM disappearance, with harmine showing a sustained effect lasting over three months after end of treatment. These findings suggest that targeting the HGF/MET/TWIST1 axis may be an effective treatment strategy for MET amplified LUAD BM."

Brain Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TWIST1

Effects of novel isoform selective HSP90 beta inhibitors alone and in combinations against experimental esophageal adenocarcinoma (AACR 2025) - "In conclusion, our data shows that NDNB21/NDNB25 exhibited potent apoptotic activity against HER2-positive EAC cells either alone or in combination."

Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Solid Tumor • CDC37 • HSP90AA1 • HSP90AB1

Patient-derived organoids as a screening platform to identify mechanisms of osimertinib resistance in non-small cell lung cancer (AACR 2025) - "The c-MET inhibitor capmatinib was specifically potent in LPTO245 but not in other models. This finding was confirmed using savolitinib, another selective c-MET inhibitor, suggesting the observed effects were due to on-target c-MET inhibition...Additionally, we identified an inverse sensitivity correlation between osimertinib and the Aurora kinase B inhibitor AZD2811 across all 6 models (r = -0.64; p = 0.03)... Our screening platform can provide novel biological insights into osimertinib resistance. Moreover, it can potentially identify drug combinations with immediate clinical utility in NSCLC, particularly with approved and clinical-grade drugs."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AURKB • BRD4 • CDK4 • EGFR • PLK1 • ROS1

Longitudinal Genomic Analysis to Fine-Tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients With BRAF V600-Mutant Metastatic Melanoma. (PubMed, Clin Cancer Res) - P2 | "LOGIC 2 supports the use of encorafenib plus binimetinib for treatment naive and previously treated locally advanced unresectable or metastatic BRAF V600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance."

Journal • P2 data • Melanoma • Oncology • Solid Tumor • BRAF

Combination Therapy with MET-TKI and EGFR-TKI in patients with MET-overexpressed EGFR-mutant Lung Adenocarcinoma (JTO Clinical and Research Reports) - "This retrospective cohort study included patients with advanced EGFR-mutant LUAD progressed after EGFR-TKIs and treated with combination therapy of EGFR-TKIs and MET-TKIs (capmatinib or tepotinib)....This study included 27 patients, aged 69 years, 40.7% male, and 88.9% never smoked. Overall, the treatment response of TKI combination showed 29.6% (8/27) partial response, 55.6% (15/27) stable disease, a median progression-free survival (mPFS) 7.3 months, and an overall survival 26.9 months. The adverse events (AE) were mostly grade 1–2, with only one patient experiencing a grade ≥3 event, which was peripheral edema."

Retrospective data • Non Small Cell Lung Cancer

Fluorescence based live cell imaging identifies exon 14 skipped hepatocyte growth factor receptor (MET) degraders. (PubMed, RSC Adv) - "We generated a library of sixty PROTACs of which 37 used the MET inhibitor capmatinib as the protein of interest targeting ligand...Curve fitting live cell imaging data affords determination of time required to degrade 50% of the target protein (DT50), which was used in determining structure activity relationships. A promising candidate, 48-284, identified from the screen, exhibited classic PROTAC characteristics, was >15-fold more potent than SJF8240, had fewer off targets compared to SJF8240, and degraded MET in multiple cell lines."

Journal • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • MET

Adverse event signal analysis of type Ib MET tyrosine kinase inhibitors based on food and drug administration adverse event reporting system. (PubMed, Expert Opin Drug Saf) - "Key PT signals included protein deficiency, scrotal edema, and chylothorax for capmatinib; edema and decreased blood albumin for tepotinib; and abnormal hepatic function for savolitinib. The study highlights differences in the safety profiles of Type Ib MET TKIs, underscoring the need for further regulatory review and possible updates to product labels to better inform clinicians and patients."

Adverse events • Journal • Hepatology • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Otorhinolaryngology • Solid Tumor • MET

MOMENT disease registry: Patient characteristics and treatment patterns from interim enrollment analysis of patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring METexon 14 (METex14) skipping treated with systemic therapy (ELCC 2025) - P | "Enrollment of the first 30% of pts into the MOMENT registry has shown that patient and disease characteristics are reflective of routine clinical care, and that MET inhibitors are being adopted into routine care in countries where the MOMENT registry is enrolling pts."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Drug repositioning as a promising approach for the eradication of emerging and re-emerging viral agents. (PubMed, Mol Divers) - "Main repositioned drugs have included chloroquine, ivermectin, dexamethasone, Baricitinib, tocilizumab, Mab114 (Ebanga™), ZMapp (pharming), Artesunate, imiquimod, saquinavir, capmatinib, naldemedine, Trametinib, statins, celecoxib, naproxen, metformin, ruxolitinib, nitazoxanide, gemcitabine, Dorzolamide, Midodrine, Diltiazem, zinc acetate, suramin, 5-fluorouracil, quinine, minocycline, trifluoperazine, paracetamol, berbamine, Nifedipine, and chlorpromazine. This succinct review will delve into the topic of repositioned drugs that have been utilized to combat emerging and re-emerging viral pathogens."

Journal • Review • Chikungunya • Dengue Fever • Ebola Virus Disease • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases

CRE25-033: A MET Amplified Metastatic Esophageal Adenocarcinoma Demonstrates Response to the MET Inhibitor Capmatinib. (PubMed, J Natl Compr Canc Netw) - No abstract available

Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Solid Tumor

Ototoxicity and safety profile of capmatinib in NSCLC: Insights from real-world FAERS data (2020–2023) (ELCC 2025) - "This study highlights unexpected ADRs associated with Capmatinib in the treatment of NSCLC with METex14 mutations, emphasizing the need for increased clinical monitoring and further investigation into the underlying mechanisms. These findings provide valuable insights into the real-world safety profile of targeted therapies."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

GeoMETry-C: Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation (clinicaltrials.gov) - P2 | N=37 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2025 ➔ Apr 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • MET

Unveiling the potential of tankyrase I inhibitors for the treatment of type 2 diabetes mellitus: A hybrid approach using network pharmacology, 2D structural similarity, molecular docking, MD simulation and in-vitro studies. (PubMed, Life Sci) - "This study highlights the role of the Wnt signaling pathway in T2DM pathogenesis and identifies potential drug candidates for repurposing as Tankyrase1/Wnt inhibitors. The findings provide a foundation for further in-vivo investigations into the anti-diabetic potential of the identified drugs, paving the way for novel therapeutic strategies in T2DM management."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CTNNB1

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2025 ➔ Oct 2025 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase II study of cabozantinib in NSCLC harboring MET exon14 alterations resistance to tepotinib or capmatinib (JSMO 2025) - No abstract available

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Molecular mechanism of type ib MET inhibitors and their potential for CNS tumors. (PubMed, Sci Rep) - "Notably, vebreltinib and capmatinib have demonstrated superior blood-brain barrier (BBB) permeability in both computational and experimental models, highlighting their potential for treating the central nervous system (CNS) metastases. Despite challenges posed by P-gp mediated efflux, vebreltinib has emerged as a promising candidate for CNS treatment due to its favorable pharmacokinetic profile and minimal susceptibility to P-gp efflux. This study underscores the importance of molecular dynamics simulations in predicting drug efficacy and BBB penetration, providing valuable insights for the development of CNS-targeted metastases therapies."

Journal • Brain Cancer • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Application of an Integrated Single-Cell and Three-Dimensional Spheroid Culture Platform for Investigating Drug Resistance Heterogeneity and Epithelial-Mesenchymal Transition (EMT) in Lung Cancer Subclones. (PubMed, Int J Mol Sci) - "Using A549 lung cancer cells, we established a cisplatin-resistant line and isolated three resistant subclones (Holoclone, Meroclone, Paraclone) via single-cell sorting. In 3D spheroids, Docetaxel and Alimta displayed higher IC50 values than in 2D cultures, suggesting that 3D models better reflect clinical dosing. Additionally, MPE-derived Holoclone and Paraclone subclones exhibited distinct sensitivities to Giotrif and Capmatinib, revealing their heterogeneous drug responses. Molecular analyses confirmed elevated ABCB1, ABCG2, cancer stem cell (CSC) markers (OCT4, SOX2, CD44, CD133), and epithelial-mesenchymal transition (EMT) markers (E-cadherin downregulation, increased Vimentin, N-cadherin, Twist) in resistant subclones, correlating with enhanced migration and invasion. This integrated approach clarifies the interplay between heterogeneity, CSC/EMT phenotypes, and drug resistance, providing a valuable tool for predicting therapeutic responses and guiding..."

Heterogeneity • Journal • Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • ABCB1 • ABCG2 • CD133 • CDH1 • CDH2 • POU5F1 • SOX2 • VIM

Capmatinib in Refractory Intrahepatic Cholangiocarcinoma (CCA) Harboring MET Amplification: A Case Report (JSMO 2025) - No abstract available

Case report • Clinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • MET

Severe Hepatotoxicity From Capmatinib: A Case Report and Therapeutic Approach. (PubMed, Cureus) - "Here, we present a case of a 60-year-old male with MET exon mutated NSCLC who developed grade 4 liver injury after capmatinib initiation, which did not respond to drug discontinuation and eventually responded to N-acetyl cysteine (NAC) and ursodeoxycholic acid (ursodiol) therapy. This case demonstrates that NAC plus ursodiol can be an effective treatment strategy in such patients."

Journal • Hepatology • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

METalmark: A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=57 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First-line MET tyrosine kinase inhibitors versus immunotherapy for patients with MET exon 14 skipping mutant metastatic non-small cell lung cancer (IASLC-TTLC 2025) - "Among those who received MET-TKI, 50% received capmatinib, 15.4% tepotinib, 28.2% crizotinib, and 6.4% another MET-TKI. Safety of MET-TKI was similar when administered as first-line or as second-line after first-line ICI. This data highlights the role of individual patient characteristics in selecting the most appropriate first-line for METex14-mutant NSCLC."

Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET • PD-L1