TPD3310: First-in-Human Phase I Trial Targeting c-MET Protein Degradation in Solid Tumors

Novel c-MET Degrader Enters First-in-Human Trial for Advanced Solid Tumors

Researchers have initiated a first-in-human clinical trial of TPD3310, a novel selective c-MET protein degrader targeting advanced solid tumors with c-MET positive mutations. The phase I trial will evaluate the safety, pharmacokinetics, and preliminary efficacy of the molecule across multiple cancer types, including lung, gastric, liver, cholangiocarcinoma, esophageal, pancreatic, and renal cancers.

The study, conducted by the Cancer Hospital Chinese Academy of Medical Sciences, will employ a standard dose-escalation design to assess TPD3310's safety profile. Patients with c-MET positive advanced solid tumors who have progressed on standard therapies will be enrolled, with an anticipated target of approximately 30 participants. The trial will explore multiple dose levels and assess pharmacodynamic markers, maximum tolerated dose, and initial signs of therapeutic activity.

Research Context

The therapeutic strategy targets the c-MET receptor tyrosine kinase, a critical driver of tumor progression through its role in cell proliferation, survival, and metastasis. Aberrant c-MET activation is associated with poor prognosis across multiple solid tumor types, making it an attractive therapeutic target.

In the same target class, several molecules are advancing through clinical development. Capmatinib (Novartis, FDA-approved) and Tepotinib (Merck KGaA, FDA-approved) represent established c-MET inhibitors for non-small cell lung cancer. Savolitinib from AstraZeneca/HUTCHMED is currently in phase III trials, targeting papillary renal cell carcinoma and non-small cell lung cancer with MET alterations.

The protein degradation approach of TPD3310 distinguishes it from traditional kinase inhibitors. By completely eliminating c-MET rather than simply inhibiting its activity, the molecule potentially offers a more comprehensive method of disrupting oncogenic signaling pathways.

Current standard treatments for advanced solid tumors typically involve combination chemotherapies, targeted therapies, and immunotherapeutics. TPD3310 represents an innovative approach that could provide an alternative for patients with c-MET positive tumors who have exhausted existing treatment options.

The trial's outcomes will be critical in determining whether this novel protein degradation strategy can translate the promising preclinical data into meaningful clinical benefits for patients with c-MET driven malignancies.

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