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    DRUG:

    tegtociclib (PF-07104091)

    i
    Other names: PF-07104091, PF 07104091, PF07104091
    Company:
    Pfizer
    Drug class:
    CDK2 inhibitor
    Related drugs:
    6d
    Pro-Tumorigenic Roles of Cyclin Dependent Kinase 2 and its Associated Cyclins in Cholangiocarcinoma Progression under High Glucose Condition. (PubMed, Arch Med Res)
    CCA cells with upregulated CDK2 and its cyclin partners in HG were more sensitive to tagtociclib at a higher dose. Cyclin E and cyclin A also regulated CCA metastasis by controlling epithelial-mesenchymal transition. Targeting CDK2 and its associated cyclins in CCA cells demonstrated therapeutic potential that requires further translational and clinical verification.
    Journal
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    CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2)
    |
    tegtociclib (PF-07104091)
    2ms
    A Study to Understand How the Body Processes [14C]PF-07104091 in Healthy Participants (clinicaltrials.gov)
    P1, N=9, Completed, Pfizer
    New P1 trial
    |
    tegtociclib (PF-07104091)
    5ms
    Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors. (PubMed, Front Oncol)
    In this study, we evaluated the effectiveness of the CDK4/6 inhibitor, palbociclib, the CDK2 inhibitor, PF-07104091, the dual CXCR1 and CXCR2 (CXCR1/2) antagonist, SX-682, and the combination of these inhibitors for effective treatment of melanoma in preclinical models. This combination also decreased the percentage of CD8+ T cells that expressed PD-1 or TIM-3 and increased the ratio of MHCII+F4/80+ M1-like macrophages to CD206+F4/80+ M2-like macrophages. These data suggest that inhibiting CDK4/6 and CDK2, combined with antagonism of CXCR1/2, may be an effective treatment for BRAF wild-type melanoma tumors and NRAS mutant melanoma tumors that express Rb and are resistant to immune checkpoint inhibitors.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • IFNG (Interferon, gamma) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • CCNA2 (Cyclin A2) • FOXP3 (Forkhead Box P3) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • CXCR2 (Chemokine (C-X-C motif) receptor 2) • MRC1 (Mannose Receptor C-Type 1)
    |
    BRAF mutation • NRAS mutation • BRAF wild-type • NRAS wild-type
    |
    Ibrance (palbociclib) • SX-682 • tegtociclib (PF-07104091)
    8ms
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P2, N=154, Active, not recruiting, Pfizer | Phase classification: P1/2 --> P2 | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026
    Phase classification • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • tegtociclib (PF-07104091)
    11ms
    18F-FLT PET, a Non-Invasive Pharmacodynamic Biomarker of Tumor Cell Proliferation, Detected Differential Response to Various Cyclin Dependent Kinase (CDK) Inhibitors. (PubMed, Mol Cancer Ther)
    Consistent with this observation, 18F-FLT PET was able to differentiate the resistance to Palbociclib from sensitivity to PF-06873600 (CDK2/4/6 inhibitor) and PF-07104091 in OVCAR-3 model. This work highlights the utility of 18F-FLT PET as a quantitative, non-invasive biomarker which provides whole-body information. 18F-FLT PET has potential to be a biomarker in novel CDK inhibitor clinical trials to evaluate Palbociclib resistance and identifying responding and non-responding patients.
    PK/PD data • Journal
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    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • ebvaciclib (PF-06873600) • tegtociclib (PF-07104091)
    1year
    Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer. (PubMed, Adv Sci (Weinh))
    Combination of CDK2 inhibitors in clinical trials (Dinaciclib or PF-07104091) and lenvatinib markedly suppressed growth of xenograft tumors from the lenvatinib-resistant patient. The findings support the combination therapy strategy of lenvatinib and CDK2 inhibitor for lenvatinib-resistant ATC patients with high CDK2 expression.
    Journal
    |
    FBXW7 (F-Box And WD Repeat Domain Containing 7) • CDK2 (Cyclin-dependent kinase 2) • RACK1 (Receptor For Activated C Kinase 1)
    |
    CDK2 expression
    |
    Lenvima (lenvatinib) • dinaciclib (MK-7965) • tegtociclib (PF-07104091)
    over1year
    C4391002: A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors (clinicaltrials.gov)
    P1/2, N=192, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Aug 2026 | Trial primary completion date: Dec 2026 --> Aug 2026
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HR positive + HER-2 positive • PTEN mutation + HR positive
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tegtociclib (PF-07104091)
    over1year
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P1/2, N=154, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=320 --> 154 | Trial completion date: Jan 2026 --> Mar 2025
    Enrollment closed • Enrollment change • Trial completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • PTEN mutation + HR positive
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • tegtociclib (PF-07104091)
    almost2years
    A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors (clinicaltrials.gov)
    P1/2, N=240, Recruiting, Pfizer | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2026 --> Dec 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HR positive + HER-2 positive • PTEN mutation + HR positive
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tegtociclib (PF-07104091)
    2years
    A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors (clinicaltrials.gov)
    P1/2, N=240, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2
    Phase classification • Combination therapy • Metastases
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HR positive + HER-2 positive
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tegtociclib (PF-07104091)
    over2years
    A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors (clinicaltrials.gov)
    P1b/2, N=240, Recruiting, Pfizer | N=144 --> 240
    Enrollment change • Combination therapy • Metastases
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HR positive + HER-2 positive
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tegtociclib (PF-07104091)
    over2years
    A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors (clinicaltrials.gov)
    P1b/2, N=144, Recruiting, Pfizer | Trial completion date: Jul 2027 --> Sep 2026
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HR positive + HER-2 positive
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tegtociclib (PF-07104091)