^
    2ms
    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) • tagtociclib (PF-07104091)
    6ms
    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 • tagtociclib (PF-07104091)
    8ms
    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) • tagtociclib (PF-07104091)
    1year
    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) • tagtociclib (PF-07104091)
    1year
    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) • tagtociclib (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)
    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) • tagtociclib (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)
    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) • tagtociclib (PF-07104091)
    over1year
    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 • tagtociclib (PF-07104091)
    over1year
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P1/2, N=320, Recruiting, Pfizer | Phase classification: P2 --> P1/2 | N=240 --> 320 | Trial completion date: Nov 2027 --> Jan 2026 | Trial primary completion date: Nov 2026 --> Jan 2025
    Phase classification • Enrollment change • Trial completion date • Trial primary 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
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • tagtociclib (PF-07104091)
    almost2years
    A Phase 1b/2 Study of PF-07220060 in Combination with PF-07104091 Plus Endocrine Therapy in Participants with BC and other Advanced Solid Tumors (clinicaltrialsregister.eu)
    P2, N=144, Ongoing, Pfizer Inc.
    New P2 trial • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HR positive + HER-2 positive
    |
    fulvestrant • letrozole • atirmociclib (PF-07220060) • tagtociclib (PF-07104091)
    2years
    Combined Inhibition of CDK2 and BCL2 Overrides Resistance to Targeting BTK and CDK4/6 in Mantle Cell Lymphoma Therapy (ASH 2022)
    Unrestrained proliferation of MCL cells is mainly driven by aberrant cyclin D1 expression and dysregulated CDK4 activity that promotes cell cycle progression from G1 to S. In our phase 1 clinical trial inhibiting CDK4/6 with palbociclib and BTK with ibrutinib (PALIBR) in recurrent MCL, the complete response rate (CR) was 42% compared to 21% in response to ibrutinib alone, despite a comparable 67% overall response rate...Indeed, combined inhibition of CDK2 with PF-07104091 and BCL2 with venetoclax (PF-VEN) cooperatively impaired growth and killed ibrutinib-resistant MAVER-1 cells, more effectively in the isogenic derivative MAVER-1R cells which we generated to recapitulate cCNV in PALIBR resistance – depletion of RB protein through translational termination mutation (W99, AAF 75%) in RB1, loss of CDKN2A and gain of CDK4...In summary, by longitudinal genomic analysis, we have provided the first evidence that 1) resistance to CDK4/6i and BTKi stems from MCL intrinsic cCNV; 2) MCL cells comprise 4 major transcriptomically distinct clusters; cluster 2 expressing copious CDK2 and BCL2 is pivotal in fueling proliferation of MCL cells in resistance; 3) cluster 3 cells also accumulate with resistance due to longevity; 4) combined inhibition of CDK2 and BCL2 overrides resistance to CDK4i and BTKi, in MCL cell lines and primary MCL cells from PALIBR resistant patient. Combined inhibition of CDK2 and BCL2, therefore, represents a mechanism-based strategy to overcome CDK4/6i and BTKi resistance in MCL therapy.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • BCL2L1 (BCL2-like 1) • IRF4 (Interferon regulatory factor 4) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • TK1 (Thymidine Kinase 1)
    |
    RB1 deletion • BCL2 expression • CCND1 expression • IRF4 expression • RB deletion • TK1 expression • CDK2 expression
    |
    Venclexta (venetoclax) • Ibrance (palbociclib) • Imbruvica (ibrutinib) • tagtociclib (PF-07104091)
    over2years
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P2, N=240, Recruiting, Pfizer | Phase classification: P1/2 --> P2 | Trial completion date: Nov 2026 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2026
    Phase classification • Trial completion date • Trial primary 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
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • tagtociclib (PF-07104091)
    almost3years
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P1/2, N=240, Recruiting, Pfizer | Phase classification: P2 --> P1/2
    Phase classification • Combination therapy
    |
    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 • tagtociclib (PF-07104091)
    3years
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P2, N=240, Recruiting, Pfizer | N=144 --> 240 | Trial completion date: Mar 2025 --> Sep 2026 | Trial primary completion date: Mar 2025 --> Sep 2025
    Clinical • Enrollment change • Trial completion date • Trial primary 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
    |
    Ibrance (palbociclib) • fulvestrant • letrozole • tagtociclib (PF-07104091)
    4years
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P2, N=144, Recruiting, Pfizer | Not yet recruiting --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    Ibrance (palbociclib) • letrozole • tagtociclib (PF-07104091)
    4years
    PF-07104091 as a Single Agent and in Combination Therapy (clinicaltrials.gov)
    P2, N=144, Not yet recruiting, Pfizer
    Clinical • New P2 trial • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    Ibrance (palbociclib) • letrozole • tagtociclib (PF-07104091)