MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC planned to initiate 1Q24

UTRECHT, The Netherlands and CAMBRIDGE, MA, USA I December 02, 2023 IMerus N.V. (Nasdaq: MRUS) (“Merus”, “the Company”, “we”, or “our”), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced updated interim clinical data on MCLA-129 from ongoing expansion cohorts in non-small cell lung cancer (NSCLC) and in previously treated head and neck squamous cell carcinoma (HNSCC) were presented at the European Society for Medical Oncology (ESMO) Asia Congress 2023.

“MCLA-129 is a very active drug in EGFRm NSCLC and we’re planning a focused investment to evaluate MCLA-129 in combination with chemotherapy, which we expect to start early in 2024,” said Bill Lundberg M.D., President, Chief Executive Officer of Merus. “We are in a fortunate position to have a strong balance sheet. We also recognize the importance of being responsible with our resources to maintain financial strength, as we plan to initiate a phase 3 trial of petosemtamab in 2L+ HNSCC by mid-2024.”  

The reported data are from three expansion cohorts in the open label trial evaluating MCLA-129 in combination with osimertinib, a third generation EGFR TKI, in treatment-naïve EGFR mutant (m) NSCLC (1L) and in EGFRm NSCLC that has progressed on osimertinib (2L+), as well as MCLA-129 monotherapy in previously treated HNSCC.

Efficacy and safety of MCLA-129, an EGFR x c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC) 

Observations in the presentation include:

  • As of an August 10, 2023 data cutoff date, 60 patients (pts) with advanced/metastatic EGFRm NSCLC were treated (16/1L, 44/2L+) 
    • In the 1L setting, 16 pts were treated, with all pts evaluable for response
      • All 16 pts experienced tumor shrinkage
      • 9 confirmed partial responses (PRs) and 3 unconfirmed PRs were observed (12/16, 75%; 95% CI 48-93) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. per investigator assessment; 11 responses were ongoing, including the 3 unconfirmed PRs
      • 94% disease control rate (DCR) (95% CI 70-100)
      • 5.1 months (range 0.5-8.5) median duration of exposure with 81% continuing treatment
    • In the 2L+ setting, 44 pts were treated, with 34 pts evaluable for response  
      • All received prior osimertinib in the 1L/2L setting, 50% as only prior therapy; 36% received prior chemotherapy
      • 11 confirmed PRs and 1 unconfirmed PR were observed (12/34, 35%; 95% CI 20-54) by RECIST v1.1. per investigator assessment, 9 responses were ongoing as of the data cutoff date, including the 1 unconfirmed PR
      • 74% DCR (95% CI 56-87)
      • 2.8 months (range: 0.3-11.5) median duration of exposure with 39% continuing treatment
  • Early safety assessment in 60 NSCLC pts treated with MCLA-129 plus osimertinib included 
    • Most common adverse events (AEs) regardless of causality were infusion related reactions (IRRs; composite term) in 87% (12% ≥ grade(G) 3)
    • Treatment emergent adverse events (TEAEs) led to discontinuations in 14 (23%) pts
    • Treatment related interstitial lung disease (ILD)/pneumonitis in 13 pts (22%), four were G1, two were G2, four were G3, and three were G5
    • Venous thromboembolic (VTE) events in 23%; 5% treatment related

Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in head and neck squamous cell cancer (HNSCC) 

Observations in the presentation include:

  • As of an August 10, 2023 data cutoff date, 22 pts with previously treated HNSCC were treated
    • 20 pts were evaluable for response   
    • Pts received a median of 3 lines of prior therapy, 22% prior chemotherapy, 20% prior anti-PD-(L) 1, 36% prior cetuximab
    • 1 confirmed and 1 unconfirmed PR were observed (2/20, 10%, 95% CI 1–32) by RECIST v1.1. per investigator assessment
      • The confirmed response was ongoing with a duration of response of 3.4+ months at data cutoff date
      • The unconfirmed PR was confirmed after the data cutoff date with treatment still ongoing at the time of presentation
    • 60% DCR (95% CI 36–81)
    • 2.2 months (range 0.5–6) median duration of exposure
  • Early safety assessment in 22 HNSCC pts treated with MCLA-129 monotherapy included
    • IRRs (composite term) in 73% (14% ≥ G3) all on cycle 1 day 1
    • Skin toxicity (composite term) in 86% (14% ≥ G3)
    • No ILD or VTE events were reported
    • No G5 TEAEs were reported

The full presentations are available on the Publications page of our website.

About Merus N.V.
Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, and

About MCLA-129
MCLA-129 is an antibody-dependent cellular cytotoxicity-enhanced Biclonics® that is designed to inhibit the EGFR and c-MET signaling pathways in solid tumors. Preclinical data have shown that MCLA-129 can effectively treat TKI-resistant NSCLC in xenograft models of cancer. MCLA-129 is designed to have two complementary mechanisms of action: blocking growth and survival pathways to stop tumor expansion and recruitment and enhancement of immune effector cells to eliminate the tumor.