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    DRUG:

    petosemtamab (MCLA-158)

    i
    Other names: MCLA-158, MCLA 158, MCLA158, LGR5 x EGFR Biclonics, Peto
    Company:
    Merus
    Drug class:
    EGFR antagonist, LGR5 inhibitor
    Related drugs:
    1d
    Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=180, Recruiting, Merus B.V. | Initiation date: Dec 2025 --> Mar 2025
    Trial initiation date
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • petosemtamab (MCLA-158)
    29d
    Recent highlights and breakthroughs in immunotherapy for head and neck cancers. (PubMed, Curr Opin Oncol)
    Recent advances highlight a rapid surge in positive immunotherapy trials across different head and neck cancer entities, with clinical benefit observed both when immune checkpoint inhibitors are moved earlier in the disease course and when they are combined with agents targeting resistance mechanisms or enabling more precise drug delivery to tumors.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Erbitux (cetuximab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Bavencio (avelumab) • Loqtorzi (toripalimab-tpzi) • AiRuiKa (camrelizumab) • Padcev (enfortumab vedotin-ejfv) • Meiyouheng (becotatug vedotin) • ficerafusp alfa (BCA101) • petosemtamab (MCLA-158) • becotarug (JMT101) • izalontamab (SI-B001) • izalontamab brengitecan (BL-B01D1) • Cotelet (tagitanlimab)
    2ms
    Beyond EGFR inhibition in Head and Neck Squamous Cell Carcinoma: overcoming resistance mechanisms and novel therapeutic frontiers. (PubMed, Crit Rev Oncol Hematol)
    Cetuximab, a chimeric IgG1 monoclonal antibody anti-EGFR, is the only EGFR-targeted agent approved for HNSCC and has shown efficacy in both locally advanced (in platinum-unfit patients) and recurrent/metastatic (R/M) settings...Irreversible pan-HER tyrosine kinase inhibitors (e.g., afatinib, dacomitinib), dual-target bispecific antibodies such as duligotuzumab (EGFR/HER3), petosemtamab (EGFR/LGR5) or ficerafusp alfa (EGFR/TGF-β) have led to promising preclinical and early-phase clinical activity...While EGFR remains a valid therapeutic target, future efforts must focus on biomarker-driven patient selection and combination strategies to enhance efficacy and durability of response. Ongoing trials will further define the role of emerging anti-EGFR agents and their integration into HNSCC treatment algorithms.
    Review • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    PIK3CA mutation
    |
    Erbitux (cetuximab) • Gilotrif (afatinib) • Vizimpro (dacomitinib) • ficerafusp alfa (BCA101) • petosemtamab (MCLA-158)
    2ms
    Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=180, Recruiting, Merus N.V.
    New P2 trial
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • petosemtamab (MCLA-158)
    10ms
    LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC. (PubMed, Future Oncol)
    LiGeR-HN2 (NCT06496178) evaluates petosemtamab versus investigator's choice of monotherapy (cetuximab, methotrexate, or docetaxel) in patients with previously treated r/m HNSCC. Primary endpoints in both trials are objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review, and overall survival. Both trials are recruiting at the time of publication.Clinical Trial Registration: NCT06525220 and NCT06496178 (ClinicalTrials.gov).
    P3 data • Journal
    |
    EGFR (Epidermal growth factor receptor) • LGR5 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 5)
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • docetaxel • methotrexate • petosemtamab (MCLA-158)
    10ms
    Petosemtamab, a Bispecific Antibody Targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G Repeat-Containing Protein-Coupled Receptor (LGR5) Designed for Broad Clinical Applications. (PubMed, Cancers (Basel))
    The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • LGR5 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 5)
    |
    PD-L1 expression
    |
    petosemtamab (MCLA-158)
    over1year
    MCLA-158-CL03: A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (clinicaltrials.gov)
    P3, N=500, Recruiting, Merus N.V. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Keytruda (pembrolizumab) • petosemtamab (MCLA-158)
    over1year
    A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Recurrent or Metastatic PD-L1+ Head and Neck Squamous Cell Carcinoma Patients (clinicaltrials.gov)
    P3, N=500, Not yet recruiting, Merus N.V.
    New P3 trial • Metastases
    |
    Keytruda (pembrolizumab) • petosemtamab (MCLA-158)
    over1year
    LiGeR-HN2: A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (clinicaltrials.gov)
    P3, N=500, Recruiting, Merus N.V. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Erbitux (cetuximab) • docetaxel • petosemtamab (MCLA-158)
    over1year
    MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=567, Recruiting, Merus N.V. | N=360 --> 567 | Trial completion date: Jun 2025 --> Nov 2027 | Trial primary completion date: Jun 2024 --> Nov 2025
    Enrollment change • Trial completion date • Trial primary completion date • First-in-human
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR amplification
    |
    Keytruda (pembrolizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • petosemtamab (MCLA-158)
    over1year
    A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (clinicaltrials.gov)
    P3, N=500, Not yet recruiting, Merus N.V.
    New P3 trial • Metastases
    |
    Erbitux (cetuximab) • docetaxel • petosemtamab (MCLA-158)
    2years
    MCLA-158-CL01: A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=360, Recruiting, Merus N.V. | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • First-in-human
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR amplification
    |
    Keytruda (pembrolizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • petosemtamab (MCLA-158)