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    DRUG:

    MCLA-129

    i
    Other names: MCLA-129, MCLA129, MCLA 129
    Company:
    Betta Pharma, Merus
    Drug class:
    EGFR inhibitor, c-MET inhibitor
    Related drugs:
    3ms
    METex14: Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR, Anti-c-MET Bispecific Antibody, in Advanced NSCLC and Other Solid Tumors, Alone and in Combination (clinicaltrials.gov)
    P1/2, N=576, Recruiting, Merus N.V. | N=380 --> 576 | Trial completion date: Apr 2025 --> Mar 2027 | Trial primary completion date: Apr 2024 --> Mar 2026
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    Tagrisso (osimertinib) • MCLA-129
    1year
    Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in head and neck squamous cell cancer (HNSCC) (ESMO Asia 2023)
    Pts received a median of 2 lines of prior systemic therapy, including anti-PD-(L)1 (78%) and platinum-based chemotherapy (89%); 28% received cetuximab in the RM setting. No cases of interstitial lung disease were reported in this cohort. Conclusions MCLA-129 monotherapy demonstrated antitumor activity in pts with pretreated RM HNSCC with a manageable safety profile.
    Clinical
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • MET expression
    |
    Erbitux (cetuximab) • MCLA-129
    1year
    Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC) (ESMO Asia 2023)
    Conclusions MCLA-129 plus osimertinib showed promising clinical efficacy in EGFRmut NSCLC, in 1L and 2L+. IRRs and ILD/pneumonitis were observed.
    Clinical
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR expression • MET expression
    |
    Tagrisso (osimertinib) • MCLA-129
    1year
    Study of MCLA-129 Combined With Befotertinib in the Treatment of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation (clinicaltrials.gov)
    P1, N=172, Not yet recruiting, Betta Pharmaceuticals Co., Ltd.
    New P1 trial • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion
    |
    MCLA-129 • Semena (befotertinib)
    over1year
    Preclinical evaluation of MCLA-129, a bispecific antibody targeting EGFR and c-MET on solid tumor cells, in comparison with amivantamab (AACR 2023)
    A phase 1/2 clinical trial of MCLA-129 in solid tumors is ongoing. These data support the further clinical development of MCLA-129 in patients with NSCLC and other solid tumors.
    Preclinical • Tumor cell
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • MET exon 14 mutation • MET mutation
    |
    Rybrevant (amivantamab-vmjw) • MCLA-129 • onartuzumab (RG3638)
    almost2years
    A Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors (clinicaltrials.gov)
    P1/2, N=380, Recruiting, Merus N.V. | N=150 --> 380
    Enrollment change • Metastases
    |
    IL6 (Interleukin 6) • IL2 (Interleukin 2)
    |
    Tagrisso (osimertinib) • MCLA-129
    2years
    MCLA-129, a human anti-EGFR and anti-c-MET bispecific antibody, in patients with advanced NSCLC and other solid tumors: an ongoing phase 1/2 study (AACR-NCI-EORTC 2022)
    At the data cut-off date of 8 May 2022, 20 pts were enrolled, across the 100, 300, 600, 1000 and 1500 mg cohorts. Median age was 65.5 years (range 43-79). Pts enrolled included: 14 pts with EGFR mutant (mt) NSCLC (4 pts L858R, 8 pts Del19, 1 pt exon 20 insertion , 1 pt with other mutation), 2 pts with c-MET exon 14 mt NSCLC, 1 pt with c-MET amplified gastric adenocarcinoma , 1 pt with squamous esophageal cancer , and 2 pts with HNSCC.
    Clinical • P1/2 data
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR L858R • MET amplification • EGFR exon 20 insertion • MET exon 14 mutation • MET mutation
    |
    MCLA-129
    over2years
    Mechanism of action of MCLA-129, a bispecific antibody that targets EGFR and c-MET and impairs growth of EGFR exon 20 insertion mutant non-small cell lung cancer (AACR 2022)
    Mutagenesis analysis identified critical binding residues of domain III of EGFR for MCLA-129 binding that are distinct from cetuximab binding. MCLA-129 is a Biclonics® common light chain bispecific antibody with multiple mechanisms of action including potent inhibition of c-MET and EGFR ligand binding, ligand-induced receptor dimerization and phosphorylation, ADCC and ADCP. MCLA-129 demonstrates significant growth inhibition of a patient-derived EGFR exon20ins tumor in a preclinical xenograft model. A phase 1/2 clinical trial of MCLA-129 in solid tumors is ongoing.
    EGFR exon 20
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Erbitux (cetuximab) • MCLA-129
    almost3years
    Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors (clinicaltrials.gov)
    P1/2, N=400, Recruiting, Betta Pharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    EGFR (Epidermal growth factor receptor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • IL1B (Interleukin 1, beta)
    |
    MET positive
    |
    MCLA-129
    over3years
    Phase 1/2 study of MCLA-129 in patients with NSCLC and other solid tumors (clinicaltrials.gov)
    P1/2; N=180; Ongoing; Sponsor:Merus N.V.
    New P1/2 trial
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR T790M • EGFR amplification • EGFR exon 20 insertion • MET exon 14 mutation • EGFR C797S • MET mutation • EGFR exon 20 mutation
    |
    FoundationOne® CDx
    |
    MCLA-129
    over3years
    Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors (clinicaltrials.gov)
    P1/2, N=400, Not yet recruiting, Betta Pharmaceuticals Co., Ltd.
    Clinical • New P1/2 trial
    |
    EGFR (Epidermal growth factor receptor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • IL1B (Interleukin 1, beta)
    |
    MET positive
    |
    MCLA-129
    over3years
    A Phase 1/2 Study Evaluating MCLA-129, a Human Anti-EGFR and Anti-c-MET Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors (clinicaltrials.gov)
    P1/2, N=150, Recruiting, Merus N.V.
    Clinical • New P1/2 trial
    |
    IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • IL1B (Interleukin 1, beta)
    |
    MCLA-129
    over3years
    [VIRTUAL] Preclinical Evaluation of MCLA-129: A Bispecific Antibody Targeting c-MET and EGFR (PEGS 2021)
    MCLA-129 is glycoengineered to enhance its Fc mediated ADCC and ADCP activity, thus allowing it to inhibit tumor growth independent of EGFR or c-MET signaling. MCLA-129 holds promise as a potential treatment option for NSCLC and other solid tumors.
    Preclinical
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MCLA-129