WCLC 2025 - Posters & ePosters-P3.18.67 First-In-Human Phase I/II Trial of PFL-002/VERT-002 in Locally Advanced or Metastatic Solid Tumors Including NSCLC With MET Alterations

P3.18.67 First-In-Human Phase I/II Trial of PFL-002/VERT-002 in Locally Advanced or Metastatic Solid Tumors Including NSCLC With MET Alterations

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Pdf Summary

This first-in-human, phase I/II open-label, multicenter trial evaluates PFL-002/VERT-002, a novel anti-MET degrader, in patients with locally advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC) harboring MET alterations. NSCLC accounts for approximately 85% of lung cancers, with 2-4% exhibiting MET exon 14 skipping mutations, associated with poor prognosis and median overall survival of 8-11 months without MET inhibitor treatment. Current MET tyrosine kinase inhibitors (TKIs) have safety limitations such as peripheral edema, gastrointestinal toxicity, and hepatotoxicity, and no approved treatments exist for patients developing resistance or with de novo MET amplification (found in 1-5% of NSCLCs), representing a significant unmet medical need.<br /><br />PFL-002 has a unique mechanism targeting MET exon 14 mutations, MET amplification, and resistance mutations to first-generation MET inhibitors, showing promising tolerability in preclinical toxicology studies and a potential for improved therapeutic index compared to existing agents.<br /><br />The study comprises two parts: Part 1 includes dose escalation in patients with various solid tumors harboring MET alterations; Part 2 focuses on NSCLC patients with METex14 mutations and/or de novo MET amplification. Key eligibility includes adults with histologically confirmed relapsed/refractory advanced tumors, appropriate MET alterations confirmed by local testing, and no recent MET TKI or other systemic anticancer therapy.<br /><br />Primary objectives are to establish safety, tolerability, and optimal dosing of PFL-002, including determination of the optimal biologically active dose (OBD), maximum tolerated dose (MTD), or maximum administered dose (MAD). Secondary objectives include pharmacokinetics, immunogenicity, and preliminary antitumor activity assessment.<br /><br />The multinational trial is ongoing across 20 sites in nine countries, with first patient dosing initiated in October 2024. This study aims to address critical gaps in treatment options for NSCLC patients with challenging MET-driven disease profiles.

Asset Subtitle

Julien Mazieres

Meta Tag

Speaker Julien Mazieres

Topic Clinical Trials in Progress

Keywords

PFL-002

VERT-002

anti-MET degrader

non-small cell lung cancer

NSCLC

MET exon 14 skipping mutation

MET amplification

phase I/II clinical trial

dose escalation

MET tyrosine kinase inhibitors