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    A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=313, Recruiting, Takeda | Phase classification: P1a/1b --> P1/2 | N=118 --> 313 | Trial completion date: Mar 2025 --> Aug 2026 | Trial primary completion date: Mar 2025 --> Aug 2026
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    Keytruda (pembrolizumab) • TAK-500
    over1year
    TAK-500 as a single agent and in combination with pembrolizumab in patients (pts) with advanced solid tumors: Rationale and design of a phase I/II study (ESMO 2023)
    Background TAK-500 is a novel immune-cell-directed antibody drug conjugate comprising the STING agonist TAK-676 conjugated to a human IgG1 anti-C-C chemokine receptor 2 (CCR2) antibody. A single-stage statistical design will be utilized for 3rd-line NS NSCLC and RCC. As of May 2023, 6 sites in the United States are recruiting; the global phase 2 is planned to start in 2024.
    Clinical • P1/2 data • Combination therapy • Metastases
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    CCR2 (C-C Motif Chemokine Receptor 2)
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    Keytruda (pembrolizumab) • TAK-500 • dazostinag (TAK-676)
    over1year
    TAK-500 is a clinical stage immune-cell directed antibody drug conjugate (iADC) inducing STING activation in CCR2-expressing intratumor myeloid cells and favorable immunomodulation (AACR 2023)
    The iADC TAK-500 and mTAK-500 induces CCR2-dependent immune cell activation and anti-tumor effect. CCR2 is highly expressed in intratumor myeloid cells from NSCLC. High CCR2 is associated with enhanced local adaptive immune responses and specific clinical/molecular tumor subsets.
    Clinical • PD(L)-1 Biomarker • IO biomarker • Immunomodulating • Immune cell
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • CD68 (CD68 Molecule) • ITGAM (Integrin, alpha M) • CCR2 (C-C Motif Chemokine Receptor 2)
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    PD-L1 expression • KRAS mutation • EGFR mutation • PD-L1 overexpression
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    Keytruda (pembrolizumab) • TAK-500
    2years
    Preclinical activity of C-C chemokine receptor 2 (CCR2)-targeted immune stimulating antibody conjugate (ISAC), motivating clinical testing of TAK-500 (SITC 2022)
    Single agent α-PD-1 treatment also resulted in a 12.5% CR rate, however, when combined, mTAK-500 and α-PD-1 treatment achieved enhanced anti-tumor response with a 37.5% CR rate. Conclusions Nonclinical antitumor activity and mechanistic insight have motivated design and clinical testing of TAK-500, a CCR2-targeted STING ISAC comprising the clinical stage STING agonist TAK-676 and a high-affinity antibody targeting human CCR2, as a single agent and in combination with pembrolizumab in adults with select locally advanced or metastatic solid tumors ( NCT05070247 ).
    Preclinical • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • CCR2 (C-C Motif Chemokine Receptor 2)
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    Keytruda (pembrolizumab) • TAK-500 • dazostinag (TAK-676)
    over2years
    A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1a/1b, N=106, Recruiting, Takeda | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
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    STING (stimulator of interferon response cGAMP interactor 1)
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    Keytruda (pembrolizumab) • TAK-500