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    DRUG CLASS:

    CDK2 inhibitor

    Related drugs:
    6d
    INX-315-01: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (clinicaltrials.gov)
    P1/2, N=150, Recruiting, Incyclix Bio | Trial completion date: Jun 2026 --> Sep 2027 | Trial primary completion date: Dec 2025 --> Jul 2027
    Trial completion date • Trial primary completion date • First-in-human
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Verzenio (abemaciclib) • fulvestrant • INX-315
    1m
    CYCAD-1: A First-in-human Dose Escalation and Expansion Study to Evaluate the Safety, and Tolerability of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=564, Recruiting, AstraZeneca | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027
    Trial completion date • Trial primary completion date • First-in-human
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • camizestrant (AZD9833)
    2ms
    INCB123667-203: Phase 2 Study of INCB123667 in Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (2025-521513-14-00)
    P1/2, N=29, Recruiting, Incyte Corp.
    New P1/2 trial • Platinum resistant
    |
    CCNE1 (Cyclin E1) • FOLR1 ( Folate receptor alpha )
    |
    FOLR1 expression
    2ms
    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
    |
    CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2)
    |
    tegtociclib (PF-07104091)
    2ms
    MAESTRA 2: Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (clinicaltrials.gov)
    P3, N=466, Recruiting, Incyte Corporation | Not yet recruiting --> Recruiting
    Enrollment open • Platinum resistant
    |
    FOLR1 ( Folate receptor alpha )
    |
    gemcitabine • paclitaxel • pegylated liposomal doxorubicin • topotecan
    3ms
    CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction. (PubMed, Nat Commun)
    In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. CRISPR knockout of p21 or p27 in palbociclib-resistant cells eliminated this synergy. Further, RNA sequencing revealed that combination treatment upregulated senescence and interferon pathways, providing mechanistic insight into the observed therapeutic synergy.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    Ibrance (palbociclib) • Kisqali (ribociclib) • cirtociclib (BLU-222)
    3ms
    CYCAD-1: A First-in-human Dose Escalation and Expansion Study to Evaluate the Safety, and Tolerability of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=564, Recruiting, AstraZeneca | N=348 --> 564
    Enrollment change • First-in-human
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • camizestrant (AZD9833)
    3ms
    INCB123667-103: Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]-INCB123667 in Healthy Male Participants (clinicaltrials.gov)
    P1, N=9, Completed, Incyte Corporation | Recruiting --> Completed
    Trial completion
    4ms
    Study of GVV858 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=205, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    fulvestrant • letrozole
    4ms
    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)
    4ms
    Study of GVV858 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=205, Not yet recruiting, Novartis Pharmaceuticals
    New P1/2 trial
    |
    fulvestrant • letrozole
    4ms
    Cyclin E1 as a driver of oncogenesis; high grade serous ovarian cancer as an exemplar. (PubMed, Crit Rev Oncol Hematol)
    The WEE1 inhibitor adavosertib and the CDK2 inhibitor INCB123667 achieved response rates of 53% and 33% respectively in platinum-resistant ovarian cancer patients whose tumours overexpressed cyclin E1. Targeting of cyclin E dysregulation via a synthetic lethality approach is therefore a key area of focus for improving treatment strategies in HGSOC and other cancers with high unmet clinical need. In this review we discuss the functions of cyclin E1, mechanisms and consequences of dysregulation, and strategies for therapeutic exploitation of cyclin E1 dysregulated tumours, combining fundamental biology with clinical perspectives.
    Review • Journal
    |
    CCNE1 (Cyclin E1)
    |
    adavosertib (AZD1775)