^
    9d
    Phase 1b Study of Dazostinag Plus Pembrolizumab After Hypofractionated Radiotherapy in Patients With Select Advanced Solid Tumors. (PubMed, Cancer Res Commun)
    Dazostinag, combined with pembrolizumab after radiotherapy, was well tolerated and demonstrated clinical activity in some patients with advanced/metastatic tumors whose disease had progressed on CPIs.
    P1 data • Journal
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    IFNG (Interferon, gamma)
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    Keytruda (pembrolizumab) • dazostinag (TAK-676)
    1m
    Identification of a Novel Linker Enabling the Bioconjugation of a Cyclic Dinucleotide for the STING Antibody-Drug Conjugate TAK-500. (PubMed, Bioconjug Chem)
    The stochastic cysteine conjugation of the dazostinag containing these linkers provided ADC TAK-500 and its mouse surrogate mTAK-500 with DAR = 4. In syngeneic tumor-bearing mouse models, mTAK-500 showed target specific antitumor activity as well as the induction of immune-stimulating cytokines.
    Journal
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    STING (stimulator of interferon response cGAMP interactor 1) • CCR2 (C-C Motif Chemokine Receptor 2)
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    plozalizumab plevistinag (TAK-500) • dazostinag (TAK-676)
    5ms
    In Situ Pro-Inflammatory Effects of Dazostinag Alone or With Chemotherapy Upon the Tumor Microenvironment of Patients With Head and Neck Squamous Cell Carcinoma. (PubMed, Cancer Res Commun)
    Utilizing CIVO and spatial profiling technology, dazostinag alone and combined with chemotherapy promoted an early pro-inflammatory response and enhanced chemotherapy-mediated cell death in the native TME of intact human HNSCC tumors.
    Journal
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    CXCL9 (Chemokine (C-X-C motif) ligand 9) • CASP3 (Caspase 3)
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    dazostinag (TAK-676)
    6ms
    Iintune-1: A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=248, Active, not recruiting, Takeda | N=374 --> 248
    Enrollment change
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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    MSI-H/dMMR
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    Keytruda (pembrolizumab) • cisplatin • carboplatin • 5-fluorouracil • dazostinag (TAK-676)
    8ms
    Reversible downregulation of HLA class I in adenoid cystic carcinoma. (PubMed, J Immunother Cancer)
    Low B2M/HLA class I expression may explain why ACCs are immunologically cold and the lack of response to ICIs. Our findings suggest that the normal cell of ACC origin exists in a B2M/HLA-class I low state, and that pharmacologic manipulation with immune activators, such as STING agonists, can restore HLA/B2M in ACCs, as supported by the promising response observed in a patient with metastatic ACC. These findings indicate a potential path to urgently needed immunotherapies.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • IFNG (Interferon, gamma) • B2M (Beta-2-microglobulin) • IRF1 (Interferon Regulatory Factor 1) • NFIB (Nuclear Factor I B) • TP63 (Tumor protein 63) • GBP1 (Guanylate Binding Protein 1) • TAP1 (Transporter 1)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab) • dazostinag (TAK-676)
    9ms
    Iintune-1: A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=374, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • 5-fluorouracil • dazostinag (TAK-676)
    over1year
    A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers (clinicaltrials.gov)
    P1, N=34, Completed, Takeda | Active, not recruiting --> Completed | N=65 --> 34
    Trial completion • Enrollment change • Checkpoint inhibition
    |
    Keytruda (pembrolizumab) • dazostinag (TAK-676)
    almost2years
    A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers (clinicaltrials.gov)
    P1, N=65, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting
    Enrollment closed • Checkpoint inhibition
    |
    Keytruda (pembrolizumab) • dazostinag (TAK-676)
    2years
    PBI-MST-01(NCT04541108) Substudy TAK-02: Intratumoral Microdosing of TAK-676 in HNSCC (clinicaltrials.gov)
    P1, N=15, Completed, Presage Biosciences
    New P1 trial
    |
    CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • GZMB (Granzyme B) • CD86 (CD86 Molecule)
    |
    carboplatin • paclitaxel • 5-fluorouracil • dazostinag (TAK-676)
    2years
    A Study of TAK-676 as Single Agent and TAK-676 in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=368, Recruiting, Takeda | Phase classification: P1 --> P1/2 | Trial completion date: Jul 2025 --> Oct 2025 | Trial primary completion date: Jul 2025 --> Oct 2025
    Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • STING (stimulator of interferon response cGAMP interactor 1)
    |
    MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • 5-fluorouracil • dazostinag (TAK-676)
    over2years
    Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced or metastatic solid tumors: Preliminary safety, PK/PD, and anti-tumor activity in a phase I dose escalation study supporting a recommended dose for expansion (RDE) (ESMO 2023)
    Conclusions Preliminary safety, PK/PD data, and anti-tumor activity support the declaration of the RDE of dazostinag 5 mg + pembro 200 mg. Expansion cohorts in colorectal and head and neck cancer are enrolling.
    Clinical • P1 data • PK/PD data • Combination therapy • PD(L)-1 Biomarker • Metastases
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    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • STING (stimulator of interferon response cGAMP interactor 1)
    |
    Keytruda (pembrolizumab) • dazostinag (TAK-676)
    over2years
    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)
    |
    Keytruda (pembrolizumab) • plozalizumab plevistinag (TAK-500) • dazostinag (TAK-676)