WCLC 2025 - Posters & ePosters-PT2.12.05 MCLA-129, an Anti-EGFR/MET Bispecific Antibody, in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC): Updated Results of a Phase 1 Study

PT2.12.05 MCLA-129, an Anti-EGFR/MET Bispecific Antibody, in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC): Updated Results of a Phase 1 Study

Back to course

Pdf Summary

The phase 1 study (NCT04930432) evaluated MCLA-129, a bispecific anti-EGFR/MET antibody, as monotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14), EGFR exon 20 insertions (20ins), or non-20ins EGFR mutations. A total of 260 NSCLC patients received varying doses (1500 mg or 2000 mg) of MCLA-129 administered intravenously every two weeks.<br /><br />Key efficacy outcomes included an overall response rate (ORR) of 45.3% in the 1500 mg cohort for METex14 patients, with even higher ORR (83.3%) in patients without prior MET-targeted therapies. Treatment-naïve METex14 patients showed an ORR of 46.2%, and those with prior MET tyrosine kinase inhibitors (TKIs) had modest responses (38.2%). For EGFR 20ins-mutant NSCLC, preliminary efficacy was noted with ORRs of 28.6% (1500 mg). Patients with non-20ins EGFR mutations showed modest activity (ORR ~25%). Median progression-free survival (PFS) ranged around 6–9.7 months for METex14 and approximately 6–7 months for EGFR mutation cohorts.<br /><br />MCLA-129 demonstrated a manageable safety profile; most treatment-related adverse events (TRAEs) were grade 1-2. The most common side effects included infusion-related reactions, hypoalbuminemia, neutropenia, leukopenia, rash, and liver enzyme increases. Grade 3 events were less frequent.<br /><br />This study highlights the promising antitumor activity of MCLA-129 in advanced NSCLC patients with METex14 and EGFR mutations, including those who had progressed on previous chemotherapy or MET TKIs. Given the encouraging safety and efficacy results, further research is warranted to explore MCLA-129 monotherapy's potential in METex14 NSCLC and to identify biomarkers (such as MET amplification or overexpression) for optimal patient selection. The investigation of dual EGFR/MET-targeting antibodies is a promising avenue in NSCLC treatment, especially for molecularly defined subgroups with limited options after standard therapies.<br /><br />In summary, MCLA-129 offers a novel, tolerable therapeutic approach with notable clinical activity against challenging NSCLC mutations, supporting expanded clinical development.

Asset Subtitle

Ma Lin

Meta Tag

Speaker Ma Lin

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

MCLA-129

non-small cell lung cancer

NSCLC

MET exon 14 skipping mutation

METex14

EGFR exon 20 insertion

EGFR mutations

bispecific anti-EGFR/MET antibody

overall response rate

progression-free survival