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    DRUG:

    tegtociclib (PF-07104091)

    i
    Other names: PF-07104091, PF 07104091, PF07104091
    Company:
    Pfizer
    Drug class:
    CDK2 inhibitor
    Related drugs:
    3ms
    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)
    6ms
    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)
    9ms
    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
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Ibrance (palbociclib) • ebvaciclib (PF-06873600) • tegtociclib (PF-07104091)
    12ms
    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)
    1year
    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)
    over1year
    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)
    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)
    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)
    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: Dec 2027 --> Jul 2027 | Trial primary completion date: Dec 2026 --> Jul 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
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tegtociclib (PF-07104091)
    over2years
    First-in-human phase 1/2a study of a potent and novel CDK2-selective inhibitor PF-07104091 in patients (pts) with advanced solid tumors, enriched for CDK4/6 inhibitor resistant HR+/HER2- breast cancer. (ASCO 2023)
    Treatment with PF-07104091 monotherapy was generally well tolerated and showed antitumor activity in heavily pretreated HR+ HER2- mBC pts who progressed on prior CDK4/6i. Dose expansions of PF-07104091 are ongoing as monotherapy in pts with ovarian cancer and in combination with fulvestrant in pts with breast cancer. Clinical trial information: NCT04553133.
    Clinical • P1/2 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    fulvestrant • tegtociclib (PF-07104091)