P3, N=147, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | N=220 --> 147

P=N/A, N=109, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

In a patient with tepotinib-induced edema and an N-terminal pro-brain natriuretic peptide (NTproBNP) level ≥ 300 pg/mL, the addition of empagliflozin to loop diuretics reduced the edema. This suggests that empagliflozin may be a treatment option for MET inhibitor-induced edema.

Molecular targeted drugs (tepotinib) showed similar efficacy for IMA harboring MET exon 14 skipping mutation to their use for NSCLC. This case suggests the benefit of aggressive multiplex genetic testing in patients with IMA and subsequent treatment with molecular targeted drugs.

P2, N=40, Recruiting, Anwaar Saeed | Not yet recruiting --> Recruiting

P2, N=32, Recruiting, University of Utah | Not yet recruiting --> Recruiting

P3, N=1000, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | Trial completion date: Jan 2032 --> Dec 2032

However, doxorubicin, foretinib, and ceritinib were identified as promising therapeutic candidates due to their low IC50 values in NCC-GCTB10-C1. The establishment of NCC-GCTB10-C1 offers a critical resource for further research into GCTB, especially in the context of recurrent disease, and holds potential for the development of more effective treatment strategies.

Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.

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.

Additionally, the combination of c-MET inhibitors with the chemotherapeutic agent doxorubicin synergistically enhanced cytotoxicity in MDR cells, as evidenced by combination index (CI) values of 0.54 ± 0.08, 0.69 ± 0.1, and 0.85 ± 0.07 for cabozantinib, crizotinib, and PHA665752, respectively...In silico analysis also suggested that the transmembrane domains (TMD) of ABCB1 transporters could be considered potential target for these agents. Our results suggest that c-MET inhibitors can serve as promising MDR reversal agents in ABCB1-medicated drug-resistant cancer cells.

This study provides compelling evidence for the safety and efficacy of CAR-M therapy in treating pancreatic cancer. The results demonstrate that CAR-M-c-MET significantly suppresses pancreatic cancer progression and enhances the effectiveness of cytotoxic chemotherapy. Remarkably, no discernible side effects occur. Further clinical trials are warranted in human pancreatic cancer patients.

Rational combinations of third-generation EGFR TKIs with anti-angiogenic drugs, chemotherapy, the EGFR-MET bispecific antibody amivantamab or local tumour ablation are being investigated as strategies to delay drug resistance and increase clinical benefit...In this Review, we describe the current first-line treatment options for EGFR-mutant NSCLC, provide an overview of the mechanisms of acquired resistance to third-generation EGFR TKIs and explore novel promising treatment strategies. We also highlight potential avenues for future research that are aimed at improving the survival outcomes of patients with this disease.

P2, N=4, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; The study was terminated early due to recruitment challenges.

P1/2, N=10, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2028 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2028 --> Nov 2024; Sponsor Withdrew Support

P2, N=365, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

P2, N=40, Not yet recruiting, Anwaar Saeed

P1/2, N=10, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=47 --> 10

P1/2, N=217, Recruiting, Janssen Research & Development, LLC | N=117 --> 217

In this study, we investigated the influence of three c-Met inhibitors, SU11274, crizotinib, and PHA665752, on molecular characteristics, tumorigenicity, and metastatic behavior in three human melanoma cell lines, M4Beu, EGFP-A375 and its metastatic variant, EGFP-A375/Rel3 (Rel3). The increased tumorigenicity of the Rel3 cells following the SU11274 treatment correlated with the elevated phosphorylation of Akt, p70 S6 and RSK kinases. Our results demonstrate pleiotropic changes induced by small-molecule inhibitors of receptor tyrosine kinases in melanoma cell lines.

P1, N=325, Active, not recruiting, Exelixis | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> Aug 2026

"Foundation Medicine, Inc. today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne Liquid CDx to be used as a companion diagnostic for TEPMETKO (tepotinib) developed by EMD Serono, the healthcare business of Merck KGaA, Darmstadt, Germany in the U.S. and Canada....FoundationOne Liquid CDx is the first FDA-approved companion diagnostic to identify patients who may be eligible for TEPMETKO."

Foretinib and elesclomol were predicted to exert strong inhibitory effects on SW13 cells by inhibiting the expression of CDH2 and CDH13. These data indicate that CDH2 and CDH13 are promising targets for precise treatment of ACC and may serve as new biomarkers for ACC prognosis.

No abstract available

P1, N=25, Recruiting, DeuterOncology | Trial completion date: Apr 2025 --> Dec 2026 | Trial primary completion date: Oct 2024 --> Dec 2025

Our findings contribute to the evolving standard of care for this specific population and highlight the clinical benefits of targeted cancer therapies.

Systemic therapy, such as chemotherapy using gemcitabine and cisplatin, is the first choice for patients with cholangiocarcinoma who were inoperable. The development of precision medicine has expanded the paradigm of targeted therapies to increasingly favorable options in the second line and beyond, and prolong overall survival. Detecting druggable mutations (mutations potentially amenable to treatment with) for identifying a landscape of therapeutic options is imperative for managing cholangiocarcinoma.

For HER2+ aBC (HER2 IHC 3+ or 2+/ISH+), 1L standard of care includes unconjugated HER2 antibodies trastuzumab and pertuzumab (HP) in combination with chemotherapy...For some targeted therapies, including MET inhibitor capmatinib, the magnitude of genomic copy number (CN) gains predict benefit... In a cohort of real-world aBC pts treated with HER2 antibody therapies, HER2 CN ratio was significantly associated with clinical outcomes. For unconjugated antibodies, pts with a HER2 CN ratio of <5 had significantly shorter TTD, PFS and OS. Future work should explore whether these pts may benefit from therapy escalation (e.g.

P2, N=365, Not yet recruiting, Janssen Research & Development, LLC

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

In vitro studies of antigen-specific T cell activation reveal significantly less inhibition of effector cytokine production and proliferation by capmatinib versus by type II or type III MET inhibitors. These findings suggest significant potential for clinical HCC combination studies of type I MET inhibitors and PD-1 blockade where prior trials using type II inhibitors have yielded limited benefit.

P2, N=29, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

P1, N=12, Recruiting, Institute of Cancer Research, United Kingdom | Not yet recruiting --> Recruiting

P3, N=1000, Not yet recruiting, Janssen Research & Development, LLC

P2, N=200, Recruiting, Janssen Research & Development, LLC | N=300 --> 200

Overall, our data indicate that c-MET directly regulates NB growth and 3D spheroid growth, and c-MET inhibition by tivantinib may be an effective therapeutic approach for high-risk NB. Further developing c-MET targeted therapeutic approaches and combining them with current therapies may pave the way for effectively translating novel therapies for NB and other c-MET-driven cancers.

P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=460 --> 701

P1, N=50, Active, not recruiting, Tavotek Biotherapeutics | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Dec 2025

P1, N=16, Completed, West China Second University Hospital

P1, N=87, Recruiting, BeiGene | Not yet recruiting --> Recruiting

Recently, amivantamab and sunvozertinib have demonstrated notable efficacy as first-line treatments, and several other promising novel targeted drugs are also challenging the status quo of traditional first-line platinum-based chemotherapy regimens. These developments are anticipated to further improve survival outcomes for NSCLC patients with EGFR ex20ins mutations. Hence, this review summarizes the epidemiology, molecular attributes, detection methodologies, and therapeutic advancements for EGFR ex20ins mutations in NSCLC, and briefly discusses the mechanisms of drug resistance.

P2, N=31, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China