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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:
    6ms
    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)
    6ms
    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 • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    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)
    almost2years
    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 • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR amplification
    |
    Keytruda (pembrolizumab) • petosemtamab (MCLA-158)
    over2years
    MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced gastric/esophageal adenocarcinoma (GEA) (AACR 2023)
    1 esophageal cancer pt died due to unrelated G5 GI bleeding. Petosemtamab demonstrated promising clinical efficacy among patients with pretreated GEA having EGFR gene amplification and/or overexpression, with a manageable safety profile.
    Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR amplification • EGFR overexpression
    |
    petosemtamab (MCLA-158)
    over2years
    Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC) (AACR 2023)
    Pts received a median of 2 (range 1-4) lines of prior systemic therapy, including anti-PD-1/PD-L1 in 96% of pts and platinum-based chemotherapy in 92% of pts; 2 pts received prior cetuximab. Petosemtamab demonstrates promising clinical efficacy with a manageable safety profile in pretreated HNSCC pts. Further clinical development in HNSCC is planned with petosemtamab monotherapy and in combination with SOC.
    Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    Erbitux (cetuximab) • petosemtamab (MCLA-158)
    almost3years
    A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=360, Recruiting, Merus N.V. | Unknown status --> Recruiting | Phase classification: P1 --> P1/2 | N=120 --> 360 | Trial completion date: Jan 2021 --> Jun 2024 | Trial primary completion date: Jan 2021 --> Jun 2023
    Enrollment open • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • LGR5 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 5)
    |
    EGFR amplification
    |
    petosemtamab (MCLA-158)
    over3years
    Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. (PubMed, Nat Cancer)
    Our drug discovery strategy resulted in the generation of MCLA-158, a bAb that specifically triggers epidermal growth factor receptor degradation in leucine-rich repeat-containing G-protein-coupled receptor 5-positive (LGR5+) cancer stem cells but shows minimal toxicity toward healthy LGR5+ colon stem cells. MCLA-158 exhibits therapeutic properties such as growth inhibition of KRAS-mutant colorectal cancers, blockade of metastasis initiation and suppression of tumor outgrowth in preclinical models for several epithelial cancer types.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    petosemtamab (MCLA-158)