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    DRUG CLASS:

    LGR5 inhibitor

    Related drugs:
    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)
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    PD-L1 expression
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    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
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    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
    QPH-FR: A Novel Quinoa Peptide Enhances Chemosensitivity by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 in Colorectal Cancer. (PubMed, J Agric Food Chem)
    Mechanistically, QPH-FR competitively suppressed the formation of the LGR5/RSPO1 complex by binding to LGR5, causing RNF43/ZNRF3 to ubiquitinate the FZD receptor, thereby suppressing the Wnt/β-catenin signaling pathway and exerting stemness inhibition. In summary, the study proposes that a novel peptide QPH-FR from quinoa elucidates the mechanism by which QPH-FR targets LGR5 to enhance chemosensitivity, providing theoretical support for the development of chemotherapeutic adjuvant drugs based on plant peptides.
    Journal
    |
    RNF43 (Ring Finger Protein 43) • RSPO1 (R-Spondin 1) • ZNRF3 (Zinc And Ring Finger 3)
    |
    5-fluorouracil
    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
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    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
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    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)
    over1year
    Leucine-rich repeat-containing G protein-coupled receptor 5 expression in lymph node metastases of colorectal cancer: Clinicopathological insights and prognostic implications. (PubMed, Pathol Int)
    LGR5 expression in LN metastases may influence prognosis. Further analysis may lead to new therapeutic strategies.
    Journal
    |
    LGR5 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 5)
    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
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    EGFR (Epidermal growth factor receptor)
    |
    EGFR amplification
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    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)