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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:
    4ms
    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)
    5ms
    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)
    5ms
    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)
    5ms
    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)
    5ms
    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)
    10ms
    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)
    almost2years
    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)
    almost2years
    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)
    almost2years
    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)
    over2years
    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)
    4years
    [VIRTUAL] Phase I dose-escalation study of MCLA-158, a first-in-class bispecific antibody targeting EGFR and LGR5, in metastatic colorectal cancer (CRC). (ASCO-GI 2021)
    Metastatic CRC pts progressing after oxaliplatin, irinotecan and fluoropyrimidines, and EGFR monoclonal antibodies if RASwt, received MCLA-158 IV every 2 weeks (q2w; 4-week cycle) in a phase I study. Dual EGFR/LRG5 blockade with MCLA-158 was well tolerated, and the RP2D was 1500 mg IV q2w. Enrollment of pts with gastric and other non-CRC cancers at the RP2D continues in the expansion phase.
    P1 data
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation
    |
    oxaliplatin • irinotecan • petosemtamab (MCLA-158)