Tabrecta (capmatinib) / Incyte, Novartis - LARVOL DELTA

A phase II study of amivantamab hyaluronidase in MET amplification–positive stage IV or recurrent non–small cell lung cancer (Lung-MAP Sub-Study). (ASCO 2026) - P2 | "Participants must have received at least one prior line of systemic therapy; notably, patients who have received prior MET TKI therapy (e.g., crizotinib, capmatinib) or harboring other actionable alterations are excluded. Correlative studies of interest include the evaluation of concordance between tissue-based and liquid biopsy (ctDNA) next-generation sequencing for the detection of MET amplification. S1900J opened to accrual on 9/27/2024 and is actively enrolling patients."

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

Amivantamab in patients with NSCLC with MET exon 14 skipping mutation: Updated results from the CHRYSALIS study. (ASCO 2022) - P1 | "Median age was 70 y (range, 43-88), 58% were women, median prior lines of therapy was 2 (range, 0-10) [eg, crizotinib (n=13), capmatinib (n=11), tepotinib (n=5), anti-MET antibody (n=1)], and 23% had history of brain metastases at baseline. Amivantamab demonstrates anti-tumor activity in primary METex14 NSCLC including after prior MET inhibitor treatment. Enrollment is ongoing and updated data will be shown."

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

Efficacy of MET-TKI in ALK-rearranged,MET-aberrant Advanced NSCLC After Resistance to ALK-TKI (IASLC-WCLC 2026) - "Five patients received crizotinib or ensartinib, while 8 patients received alectinib/lorlatinib combined with savolitinib/vebreltinib/capmatinib. Lung cancer drug-sensitive organoids could offer personalized medication guidance. Further research is needed for further exploration in the future."

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

A Multicenter Randomized Phase III Trial Comparing MET Tyrosine Kinase Inhibitors vs. Immune Checkpoint Inhibitors With or Without Chemotherapy as First-Line Treatment for Patients With Advanced Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutations: JCOG2506 (DECIDE-MET). (PubMed, Clin Lung Cancer) - P3 | "This trial aims to provide evidence to inform optimal first-line treatment strategies for advanced METex14-mutant NSCLC and to address an evidence gap in this rare population."

Checkpoint inhibition • IO biomarker • Journal • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Computational Repurposing of FDA-Approved Drugs as Candidate MMP2 Inhibitors with Putative MMP3 Cross-Activity. (PubMed, Int J Mol Sci) - "Among them, Regorafenib (S1178) and Capmatinib (S2788) showed the most favorable cross-target profiles and were further supported by MD analysis. From these findings, S1178 and S2788 were proposed as promising MMP2-prioritized compounds with potential MMP3 cross-activity, warranting further experimental validation as candidate antifibrotic MMP modulators."

FDA event • Journal • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • MMP2 • MMP3

Targeting Both Oncogenic Signaling and Dependence Receptor Function is Required to Fully Suppress MET Exon 14 Skipping-Driven tumorigenesis. (PubMed, Cancer Res) - "Importantly, inducible re-expression of p40MET in METex14Del-expressing cells restored apoptotic sensitivity, decreased tumor formation in vivo, and resensitized tumors to capmatinib. Together, these findings redefine RTKs as receptors with dual oncogenic and tumor-suppressive functions and show that disruption of dependence receptor-mediated apoptosis is an oncogenic mechanism. These results provide a conceptual framework explaining why therapies targeting only RTK signaling may fail and support strategies restoring dependence receptor function to achieve durable tumor suppression."

Journal • Oncology • MET

Capmatinib plus nivolumab in pretreated patients with EGFR wild-type advanced non-small cell lung cancer. (PubMed, Lung Cancer) - P2 | "Capmatinib plus nivolumab showed clinical activity and manageable safety in pretreated patients with advanced EGFR wild-type NSCLC, independent of MET status."

IO biomarker • Journal • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Understanding tumor adaptations and resistance to MET inhibitors in MET-altered non-small cell lung cancer. (PubMed, Neoplasia) - "MET inhibitor resistance in this cohort involved overlapping, context-dependent genomic, phenotypic, and signaling adaptations, supporting combination strategies for MET-altered lung cancer."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FN1

Efficacy of Sequential ALK- and MET-TKI Combinations for Treating ALK-rearranged NSCLC With Acquired MET Amplification (IASLC-WCLC 2026) - "The patient initiated a combination of brigatinib and the ALK/ROS1/MET-TKI, crizotinib, with disease control for nine months...Based on these results, a combination of the ALK-TKI, alectinib, and more potent MET-TKI, capmatinib, was initiated...Nevertheless, this case, in which first low-level and then high-level MET amplification emerged as ALK-TKI-resistance, suggests that both amplification levels may be effectively targeted. Thus, sequential combinations of ALK- and MET-TKIs may provide meaningful clinical benefits in patients with ALK -rearranged NSCLC acquiring MET amplification at increasing levels."

Clinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Respiratory Diseases • Solid Tumor • ALK • EML4 • MET • ROS1 • TP53

Real-world safety assessment of MET-targeted therapies: a pharmacovigilance analysis using the FAERS database. (PubMed, Drugs Context) - "In cluster analysis, key adverse drug reactions (e.g. infusion-related reactions for amivantamab, hepatotoxicity for savolitinib, peripheral swelling for capmatinib and peripheral oedema for tepotinib) primarily occur as isolated events with limited co-occurrence of multiple toxicities. These findings support individualized monitoring and evidence-based treatment selection for older patients, those with comorbidities or patients at high risk with MET-altered NSCLC."

Adverse events • Journal • Real-world evidence • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • HGF

Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial. (PubMed, Lancet Oncol) - P2 | "These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC."

Journal • P2 data • Cardiovascular • Hepatology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK • EGFR • MET

Management of Adverse Events Associated with MET TKIs in Patients with Advanced NSCLC: A Podcast Discussion. (PubMed, Target Oncol) - "Among these MET TKIs, tepotinib and capmatinib are globally approved and have demonstrated robust and durable efficacy in patients with METex14 skipping NSCLC in the VISION and GEOMETRY mono-1 trials. They will also share their perspectives on the current landscape of MET TKIs in METex14 skipping NSCLC, commonly reported TRAEs in clinical practice, management strategies for these TRAEs, and safety considerations when switching one MET TKI to another. In addition, authors will discuss two patient cases to illustrate effective management of TRAEs associated with MET TKIs in patients with METex14 skipping NSCLC."

Adverse events • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Improving public cancer care by implementing precision medicine in Norway (clinicaltrialsregister.eu) - P1/2 | N=1000 | Recruiting | Sponsor: Oslo University Hospital HF | N=6000 ➔ 1000

Enrollment change • Oncology

Phase II study of cabozantinib in patients with MET-altered lung cancers (ESMO 2023) - P2 | "Most pts (84%, 20/24) received a prior MET TKI (crizotinib, n=15; capmatinib, n=4; tepotinib, n=1); 16 pts (67%) and 13 pts (54%) received one or more prior lines of chemotherapy and immunotherapy, respectively...Due to its alternative type II binding mode, cabozantinib can be useful in the treatment of type I TKI resistance. As proof of concept, 3 of 4 responses were observed in patients with type I MET TKI progression."

Clinical • IO biomarker • P2 data • Lung Cancer • Oncology • Solid Tumor • MET

Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer. (PubMed, Eur J Cancer) - P1/2 | "Capmatinib plus nazartinib showed antitumor activity in patients with EGFR-TKI-resistant, EGFR-mutated NSCLC. The overall safety profile was acceptable."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Real-world outcomes comparison between the MET inhibitors (METi) capmatinib and tepotinib in patients with stage IV non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation. (ASCO 2024) - "We performed the first real-word comparison between cap and tep. The results demonstrated similar outcomes with both drugs, and no significant differences in AE, suggesting these agents can be employed equivalently. Importantly, rates of therapy discontinuation and dose reduction were high with both, indicating the importance of closely monitoring these pts."

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

Clinicopathologic Characteristics of Non–Small Cell Lung Carcinoma With C-MET Alterations (CAP 2026) - "Context: C-mesenchymal–to–epithelial transition (C-MET) alterations such as MET exon 14–skipping mutations (METex14) and MET amplifications (METamp) are seen in up to 5% of non–small cell lung carcinoma (NSCLC) cases and are targetable by MET tyrosine kinase inhibitors (TKIs): capmatinib, tepotinib, and crizotinib. Our study finds that MET alterations in NSCLC are aggressive carcinomas, presenting with advanced disease, and poor prognosis, and that adenocarcinoma morphology with MET alterations may be associated with MET alterations other than MET exon 14–skipping mutation. Baskota received honorarium from AstraZeneca."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • EGFR • MET • PD-L1 • TP53

A pretreatment 15-gene signature predicts non-pCR in response to neoadjuvant chemotherapy in breast cancer and reveals a pyruvate-CCND1-MET therapeutic vulnerability. (PubMed, Front Oncol) - "Functional assays and RNA-seq tested pyruvate effects and MET inhibition (capmatinib)...Single-cell analyses showed highest CCND1 expression in epithelial/malignant compartments and supported a YAP1-HIF1A/ARNT-MET transcriptional axis linking pyruvate-associated cues to MET activation. A pretreatment 15-gene RS enables risk stratification for NAC non-pCR, and mechanistic evidence supports a pyruvate-CCND1-MET vulnerability potentially addressable by MET-targeted combination strategies."

Gene Signature • Journal • Breast Cancer • Oncology • Solid Tumor • CCND1 • HIF1A • TNFA • YAP1

A Noncanonical MET Exon 14 Splice-Site Variant in Pulmonary Sarcomatoid Carcinoma With Response to Capmatinib. (PubMed, Thorac Cancer) - "We report a patient with pulmonary sarcomatoid carcinoma harboring a noncanonical MET splice donor-proximal indel (c.3022_3028 + 13delinsA), initially interpreted as a VUS, who achieved a rapid and durable response to capmatinib. Subsequent RNA sequencing and droplet digital PCR (ddPCR) confirmed MET exon 14 skipping, supporting the value of orthogonal transcript-level validation for exon-adjacent variants."

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

Capmatinib for High-Level MET-Amplified Metastatic Gastric Cancer Identified by Comprehensive Genomic Profiling: A Case Report and Literature Review. (PubMed, J Gastrointest Cancer) - "The response was maintained at 16 weeks; disease progression was observed at 24 weeks, with a progression-free survival of approximately 5.5 months. In the context of a literature review of MET-targeted therapies in gastric cancer, this case supports further investigation of selective MET inhibition in gastric cancer with high-level MET amplification, a rare molecular subset not prospectively enriched in previous clinical trials."

Journal • Review • Gastric Adenocarcinoma • Gastric 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: Jun 2026 ➔ Apr 2027

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

Targeting MET in 2025: From Exon 14 Skipping to MET-Amplified Acquired Resistance in Non-Small Cell Lung Cancer. (PubMed, Int J Mol Sci) - "Selective type Ib MET tyrosine kinase inhibitors (capmatinib, tepotinib) anchor first-line therapy for METex14, while next-generation agents and type II inhibitors are being developed to address on-target D1228 and Y1230 resistance mutations. In parallel, MET amplification has emerged as a leading mechanism of acquired resistance to osimertinib in EGFR-mutated NSCLC, with the SAVANNAH, SACHI, and INSIGHT 2 trials providing biomarker-guided combination strategies. The 2025 accelerated approval of telisotuzumab vedotin for c-Met-overexpressing tumors expanded the therapeutic armamentarium beyond kinase inhibition...This review integrates the molecular biology, current clinical evidence, resistance mechanisms, and a proposed 2025 treatment algorithm for MET-altered NSCLC, with emphasis on the translational interface between mutation class, drug class, and emerging combinatorial approaches. As a narrative review, it synthesizes peer-reviewed literature and pivotal trial and..."

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

Capmatinib and paclitaxel combination: a novel strategy for overcoming challenges in triple-negative breast cancer treatment. (PubMed, BMC Cancer) - "CAP enhances the antitumor activity of PTX in TNBC by targeting c-Met-mediated pathways. This combination therapy shows potential to overcome resistance and improve treatment outcomes in TNBC."

Journal • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDH1 • FOXC1 • FOXM1 • VIM

Geometry-N: Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC (clinicaltrials.gov) - P2 | N=38 | Recruiting | Sponsor: Novartis Pharmaceuticals | Initiation date: Dec 2021 ➔ Mar 2022

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

A Post Approval Commitment Study on Tabrecta® (Capmatinib) in South Korea (clinicaltrials.gov) - P=N/A | N=44 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=250 ➔ 44

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor