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    DRUG:

    cirtociclib (BLU-222)

    i
    Other names: BLU-222, BLU222, BLU 222
    Company:
    Sanofi, UT MD Anderson Cancer Center
    Drug class:
    CDK2 inhibitor
    Related drugs:
    1d
    CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen. (PubMed, NPJ Breast Cancer)
    Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1)
    |
    HR positive • HER-2 negative
    |
    Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    6d
    (VELA) Study of BLU-222 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=50, Terminated, Blueprint Medicines Corporation | Phase classification: P1/2 --> P1 | N=366 --> 50 | Trial completion date: Sep 2026 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2025 --> Jul 2025; This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.
    Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
    |
    HER-2 negative
    |
    carboplatin • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    10ms
    Profiling the Activity of the Potent and Highly Selective CDK2 Inhibitor BLU-222 Reveals Determinants of Response in CCNE1-Aberrant Ovarian and Endometrial Tumors. (PubMed, Cancer Res)
    BLU-222 demonstrated robust activity in combination with carboplatin or paclitaxel in CCNE1-aberrant models, rendering chemotherapy-resistant tumors strongly sensitive to the combination. These findings demonstrate that response to CDK2 inhibition by BLU-222 can be further predicted using a combinatorial biomarker signature that could refine patient selection criteria in CCNE1-high patients and support clinical development.
    Journal
    |
    CCNE1 (Cyclin E1)
    |
    carboplatin • paclitaxel • cirtociclib (BLU-222)
    11ms
    (VELA) Study of BLU-222 in Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=366, Active, not recruiting, Blueprint Medicines Corporation | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
    |
    HER-2 negative • CCNE1 amplification
    |
    carboplatin • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    over3years
    A first-in-human phase I/II study of BLU-222, a potent, selective CDK2 inhibitor in patients with CCNE1-amplified or CDK4/6 inhibitor-resistant advanced solid tumors (ESMO 2022)
    Preclinically, BLU-222 has shown potent CDK2 inhibition and antitumor activity, and combination with carboplatin/paclitaxel led to significant tumor regression. Phase II dose expansion: part 2A (CCNE1-amplified tumors including EC [≥2 prior therapies], platinum-resistant/refractory OC, or other advanced solid tumors [progression on SOC]; BLU-222], part 2B and 2D (CDK4/6i-resistant ER+HER2- BC; BLU-222 and fulvestrant with/without ribociclib), part 2C (CCNE1-amplified platinum-resistant/refractory OC; BLU-222 and carboplatin). Approximately 50 sites are anticipated to enroll patients across North America, Europe, and Asia/Pacific.
    Clinical • P1/2 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCNE1 (Cyclin E1)
    |
    ER positive • HER-2 negative • CCNE1 amplification • CDK4 amplification • CCNE1 expression
    |
    carboplatin • paclitaxel • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    over3years
    (VELA) Study of BLU-222 in Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=366, Recruiting, Blueprint Medicines Corporation | Trial completion date: Dec 2025 --> Sep 2026
    Trial completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
    |
    HER-2 negative • CCNE1 amplification
    |
    carboplatin • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    over3years
    BLU-222, an investigational, potent, and selective CDK2 inhibitor, demonstrated robust antitumor activity in CCNE1-amplified ovarian cancer models (AACR 2022)
    These data provide a strong rationale for advancing BLU-222 towards clinical development in patients with CCNE1-amplified ovarian cancer.
    Preclinical
    |
    CCNE1 (Cyclin E1) • CDK1 (Cyclin-dependent kinase 1)
    |
    CCNE1 amplification • CCNE1 overexpression
    |
    carboplatin • cirtociclib (BLU-222)
    almost4years
    (VELA) Study of BLU-222 in Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=366, Recruiting, Blueprint Medicines Corporation
    New P1/2 trial • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
    |
    HER-2 negative • CCNE1 amplification
    |
    carboplatin • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)