Tabrecta (capmatinib) / Incyte, Novartis - LARVOL DELTA

Endothelial cell-derived mitochondrial transfer to Acute Myeloid Leukemia alters global gene expression to confer chemoresistance (ASH 2025) - "When AML cellswith and without EC-derived mitochondria were isolated using FACS sorting and exposed to cytarabine oridarubicin, those with EC-derived mitochondria were significantly more chemoresistant, even withconcentrations of chemotherapy that were 10x greater than used clinically.To elucidate the mechanism behind the EC mitochondria transfer induced chemoresistance, weperformed single cell RNAseq (scRNAseq) of AML cells co-cultured with ECs. Moreover, treatmentwith capmatinib, a HGF receptor (MET) inhibitor, effectively reversed the chemoresistant phenotype ofthe AML cells containing EC-derived mitochondria, restoring sensitivity to levels comparable to controlAML cells.This research elucidates a novel mechanism whereby EC-AML interactions promote chemoresistancethrough altered AML gene expression that occurs following mitochondrial transfer from EC cells. Thespecific identification of EC mitochondrial transfer and the genetic changes that occur as a result..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • MET

MET testing and treatment (tx) sequencing after progression of disease (PD) on first-line (1L) osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and acquired MET overexpression and/or amplification (OverExp/Amp): Final analysis of a global real-world (rw) study (ESMO Asia 2025) - P2 | "Background: In the phase II SAVANNAH study (NCT03778229), osi 80 mg QD + savolitinib 300 mg BID demonstrated clinically meaningful and durable responses in EGFRm advanced NSCLC with MET OverExp/Amp after PD on 1L osi...MET-TKIs (tepotinib 52%, capmatinib 31%) and EGFR-TKIs (osi 91%) were the most common 2L txs (29% and 24%), followed by chemotherapy (CT 20%; most frequently platinum doublet 73%)... In this rw analysis, most pts had acquired MET Amp detected with NGS and limited detection of OverExp/Amp with IHC/FISH, likely indicating underutilisation of these assays. MET-TKIs and 3rd-gen EGFR-TKIs were most commonly used following PD on 1L osi and in pts with high MET cutoffs."

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

Clinical utility of cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) next generation sequencing (NGS) for diagnosis and treatment of leptomeningeal metastasis (LM) in patients with non-small cell lung cancer (NSCLC): A multi-centre retrospective study (ESMO Asia 2025) - "One showed acquired MET exon 14 skipping alteration in ctDNA, thus capmatinib was added on top of EGFR targeted therapy. One had known EGFR exon 19 deletion with negative CSF cytology showed T790M mutation in ctDNA and treatment was switched to osimertinib. In patients with NSCLC and LM symptoms, CSF ctDNA had higher sensitivity compared to cytology in LM diagnosis. In patients with NSCLC and LM symptoms, CSF ctDNA had higher sensitivity compared to cytology in LM diagnosis. CSF ctDNA may also detect actionable resistance mechanisms in guiding treatment. Further research is required to study the role of CSF ctDNA NGS in diagnosis and treatment of LM."

Biomarker • Circulating tumor DNA • Next-generation sequencing • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • MET

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=603 | Active, not recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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 completion date: May 2028 ➔ Mar 2027

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

MET-CAR cytokine induced killer lymphocytes: A novel immunotherapy for malignant pleural mesothelioma (ESMO-IO 2025) - "MPM cell dependence on MET-signalling was excluded by measuring MPM cell growth in the presence of Capmatinib, a clinically approved MET inhibitor...We successfully generated CIKs expressing MET or MSLN CARs. They were endowed with robust, dose-dependent, and comparable killing functions, superior to those of the unmodified CIKs against all the MPM models tested.Conclusions MET CIKs represent an effective therapeutic approach, an alternative to MSLN targeting immune effectors for MPM treatment.Legal entity responsible for the study The authors."

IO biomarker • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • IFNG • IL2 • MSLN • NKG2D

Case of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer with Papillary Thyroid Carcinoma (APSR 2025) - "It was found across histologies, but most commonly in sarcomatoid histology. MET TKIs, tepotinib and capmatinib, appear to result in better clinical outcomes (ORR, median PFS, and OS) than regimens with no targeted therapies."

Clinical • IO biomarker • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Palliative care • Pneumonia • Pulmonary Disease • Respiratory Diseases • Sarcoma • Septic Shock • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • MET • PD-L1 • TG

Capmatinib for the treatment of METex14 skipping non-small cell lung cancer: retrospective analysis of real-world data from patients receiving compassionate use treatment in Italy. (PubMed, Clin Exp Med) - "Twenty-four patients (45.3%) discontinued treatment; the most frequent reason for discontinuing treatment was disease progression, with a median estimated time to treatment discontinuation of 15.2 months. This real-world retrospective analysis confirms that capmatinib is a valuable treatment option for difficult-to-treat METex14 skipping NSCLC, in agreement with the data from the registration trial."

IO biomarker • Journal • Real-world evidence • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Small molecule MET kinase inhibitors: Evolution, rational design, and early clinical knowledge. (PubMed, Life Sci) - "The story of the development of these inhibitors is traced here from initial, non-selective lead molecules such as K252a to the clinically approved drugs like Capmatinib and Tepotinib. A critical analysis of the failures of previous clinical trials underscores the crucial role of robust, biomarker-driven patient selection and the use of physiologically relevant preclinical models. Finally, the successful development of contemporary MET inhibitors for cancers with specific alterations, such as MET exon 14 skipping, serves as a paradigm of iterative oncology learning, wherein early failures have given rise to precision medicine and enhanced therapeutic outcomes."

Journal • Review • Oncology

A Concise Review of the Approved MET TKIs (Savolitinib, Gumarontinib, Vebreltinib, Tepotinib, Capmatinib) in China for MET Exon 14 Splice Site Mutated (METex14+) NSCLC Circa 2025. (PubMed, Lung Cancer (Auckl)) - P3 | "Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

The Role of Concomitant MET Amplification and High PD-L1 Expression in Non-Small Cell Lung Cancer: A case report of Implications for Targeted Therapy and Immunotherapy (SITC 2025) - "Immunohistochemistry confirmed primary lung adenocarcinoma (Jan 2022) and 6 cycle of Palliative first line Chemotherapy with inj. Nab- Paclitaxel + Carboplatin + Denosumab, completed on 11 June 2022 .Results Due to poor response with 1st line CnT, 6 cycle of 2nd line palliative ChT-IO with Atezolezumab + Pemetexed + Carboplatin + Denosumab followed by Maintenance Chemo IO with Pemetrexed + Atezolizumab from 20.03.2023 till on 5/06/23...Due to poor PS & PD Targeted therapy with Capmatinib (400mg twice daily) started since Nov 2023 and patient hoarseness of voice completely improved also MRI of brain showed no metastatic deposit in brain...Then patient expired after intolerance and jaundice with sepsis on June 2024.Conclusions This case highlights the complexities of managing NSCLC with co-occurring MET amplification and high PD-L1, underscoring the importance of comprehensive molecular profiling and personalized treatment strategies. Further research into the..."

Case report • Clinical • IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • PD-L1

Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway. (PubMed, Cell Death Dis) - "All these molecular and biological effects were inhibited by trametinib, a MEK inhibitor, which was potentiated by combination with capmatinib, a MET inhibitor. Thus, we report an original and powerful strategy to uncover key regulators, including transcription factors that have not been widely described in METex14Del signaling, such as SMAD3. These factors are activated by specific signaling pathways and could provide a novel therapeutic strategy involving a combination of receptor and signaling inhibitors."

Journal • Lung Cancer • Oncology • Solid Tumor • ETS1 • FOSL1 • MET • SMAD3

Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway (Nature, Cell Death Dis) - "All these molecular and biological effects were inhibited by trametinib, a MEK inhibitor, which was potentiated by combination with capmatinib, a MET inhibitor. New mapping with transcriptomic data from trametinib-treated METex14Del cells validated the key role of the RAS-ERK pathway signaling in the activation of ETS1, FOSL1 and SMAD3 regulators and the induction of their target genes in HGF-activated METex14Del receptor."

Preclinical • Oncology

Comprehensive map of the regulatory network triggered by MET exon 14 skipping reveals important involvement of the RAS-ERK signaling pathway (Nature, Cell Death Dis) - "All these molecular and biological effects were inhibited by trametinib, a MEK inhibitor, which was potentiated by combination with capmatinib, a MET inhibitor. New mapping with transcriptomic data from trametinib-treated METex14Del cells validated the key role of the RAS-ERK pathway signaling in the activation of ETS1, FOSL1 and SMAD3 regulators and the induction of their target genes in HGF-activated METex14Del receptor."

Preclinical • Oncology

Real world adoption of off-label combination treatment to treat non-small cell lung cancer resistance (AACR-NCI-EORTC 2025) - "The median duration of treatment with off-label combination therapy was 7 months (range: 1-35 months), and was longest for alectinib and capmatinib (15 months ongoing & 25 months, ongoing) and gefitinib and selpercatinib (35 months, ongoing). Evidence to support combination regimens included retrospective cohort studies (n=3), published case reports/series (n=3), and a prospective cohort study (n=1).ConclusionOff-label combination therapy to treat targeted therapy resistance in advanced NSCLC is feasible in an academic health-safety net setting. Additional real-world evidence is needed to clarify best practices with this emerging approach."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EML4

Tolerance and efficacy of targeted therapies after immunotherapy in metastatic non-small cell lung cancer with molecular alterations: TOXIMAD GFPC 04-2022 study (ESMO 2025) - "For the efficacy, the results appear to be similar to those reported in the literature for capmatinib, dabrafenib-trametinib, crizotinib. Larger real-life studies are needed to better understand the mechanism of these AEs. Legal entity responsible for the study GFPC."

Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • HER-2 • KRAS

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 completion date: Apr 2026 ➔ May 2028

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

Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib. (PubMed, J Clin Med) - "Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types."

Biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • GAS6 • MET • TGFB1

NEXT-GENERATION SEQUENCING IN IDH-WILDTYPE GLIOBLASTOMA: A PATHWAY TO PRECISION THERAPEUTICS (EANO 2025) - "Two patients had PIK3CA mutation (targeted therapy Alpesilib), one patient has RET mutation (targeted therapy Selpercatinib & Pralsetinib), one patient had GOPC-ROS1 fusion (targeted therapy Crizotinib, Entrectinib & Repoctrectinib), one patient had PTPRZ1-MET fusion (targeted therapy Capmatinib & Tepotinib) and one patient had FGFR3-TACC3 fusion (targeted therapy Erdafitinib, Anlotinib, etc). However ongoing research is going on to overcome BBB like using nanocarriers, combination with immunotherapy or chemotherapy, etc. Although we have limitation of cases, 50% of our cases have shown mutation or fusion, against which targeted therapy is available. This holds future promise for targeted therapy for IDH-wild type glioblastoma."

Biomarker • IO biomarker • Next-generation sequencing • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • FGFR3 • PIK3CA • PTPRZ1 • RET • ROS1 • TACC3

Fe-MOF loaded with capmatinib to reverse immunosuppressive microenvironment and inhibit tumor metastasis after radiofrequency ablation. (PubMed, J Nanobiotechnology) - "In vitro and in vivo experiments confirm that Fe-MOF/Cap is able to significantly inhibit the lung metastasis of HCC after iRFA by inhibiting the c-MET/STAT3/VEGF pathway. Fe-MOF/Cap provides a potentially promising strategy for HCC immunotherapy and anti-metastasis after iRFA, with favorable clinical prospects."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • MET

Fe-MOF loaded with capmatinib to reverse immunosuppressive microenvironment and inhibit tumor metastasis after radiofrequency ablation (J Nanobiotechnology) - "Herein, an iron-based metal-organic framework loaded with capmatinib (Fe-MOF/Cap) is employed to reverse the immunosuppressive microenvironment dominated by M2-like tumor-associated macrophages (TAMs) after iRFA and inhibit lung metastasis of HCC. On one hand, Fe-MOF/Cap repolarizes M2-like TAMs to M1-like TAMs and inhibits the expression of PD-L1 after iRFA, promoting CD8+ T cell infiltration. The infiltration of CD8+ T cells and the decrease of PD-L1 are conducive to enhance the immunotherapy after iRFA. On the other hand, Fe-MOF/Cap can inhibit lung metastasis of HCC via inhibiting the expression of c-MET."

Preclinical • Hepatocellular Cancer

Function of histamine-driven cancer-associated fibroblast and hepatocyte growth factor in the progression of cholangiocarcinoma. (PubMed, Gastroenterol Rep (Oxf)) - "HIF-1α and FOSL1 played crucial roles in driving the proliferation, invasion, and migration of cholangiocarcinoma cells within the tumor microenvironment, orchestrated by CAFs. Furthermore, this study has provided theoretical support for the application of the HA receptor HRH2 inhibitor, Cimetidine, and the HGF receptor cellular mesenchymal-epithelial transition factor (c-MET) inhibitor, Capmatinib, in biliary tract tumors."

Journal • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CAFs • FOSL1 • HGF • HIF1A • HRH2 • MET • MMP10

PTEN loss and ERBB2/ERBB3-mediated AKT reactivation drive resistance to MET inhibition in MET-amplified hepatocellular carcinoma. (PubMed, Cell Oncol (Dordr)) - "Our study identifies PTEN deficiency and ERBB2/ERBB3-mediated reactivation as key resistance mechanisms to MET inhibition in MET-amplified HCC. The findings support biomarker-informed combination strategies and underscore the importance of stratifying patients based on MET amplification status."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • PTEN

The Efficacy of Capmatinib in Treating NSCLC Patients With MET Amplification in a Multi-Center Real-World Setting (IASLC-WCLC 2025) - "The MET GCN holds potential as a biomarker for predicting the efficacy of capmatinib in treating patients with MET amplification. Moreover, the fact that adverse events are manageable further validates its application in clinical practice."

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

Real-World Outcomes of Full and Reduced Dose Capmatinib and Tepotinib Treatment for MET Exon 14 Skipping Mutation NSCLC (IASLC-WCLC 2025) - "41 (95%) patients had not previously received MET targeted therapy, 2 had received crizotinib. Median PFS is similar to previous real-world analysis (Correia et al, JCO 2024). These data suggest that in older patients, often with comorbidities, or patients with AE necessitating dose reduction, patients have similar benefit to MET TKI."

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