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    DRUG:

    PRT2527

    i
    Other names: PRT2527
    Company:
    Prelude Therap
    Drug class:
    CDK9 inhibitor
    Related drugs:
    3ms
    PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer. (PubMed, Front Oncol)
    Increased MCL1 activity has been described as a resistance mechanism to Sunitinib and Everolimus, two approved agents for ccRCC. PRT2527, a potent CDK9 inhibitor which depletes MCL1, was similarly efficacious in monotherapy and in combination with Sunitinib in PBRM1-loss cells. Taken together, these findings suggest PBRM1 loss is associated with MCL1i sensitivity in ccRCC and provide rationale for the evaluation of PRT1419 and PRT2527 for the treatment for PBRM1-deficient ccRCC.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • PBRM1 (Polybromo 1)
    |
    PBRM1 mutation
    |
    sunitinib • everolimus • PRT1419 • PRT2527
    5ms
    A Study of PRT2527 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=30, Completed, Prelude Therapeutics | Active, not recruiting --> Completed
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    HR positive • HER-2 negative • MYC amplification
    |
    PRT2527
    5ms
    A Phase 1 Study Evaluating PRT2527, a Potent and Highly Selective CDK9 Inhibitor, As Monotherapy and in Combination with Zanubrutinib in Patients with Select Relapsed/Refractory B-Cell Malignancies (ASH 2023)
    The study is open to enrollment and registered at ClinicalTrials. gov (NCT05665530).
    Clinical • P1 data • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2) • BMF (Bcl2 Modifying Factor)
    |
    Brukinsa (zanubrutinib) • PRT2527
    5ms
    PRT2527, a Novel Highly Selective Cyclin-Dependent Kinase 9 (CDK9) Inhibitor, Has Potent Antitumor Activity in Combination with BTK and BCL2 Inhibition in Various Lymphoid Malignancies (ASH 2023)
    In a similar fashion, Venetoclax-driven BCL2 inhibition also potentiated the anti-tumor activity of PRT2527...Additionally, we demonstrated that PRT2527 potently inhibits growth in Ibrutinib-resistant MCL cell lines. Further work characterizing PRT2527 as monotherapy and in combination with BTKi and BCL2i in in vivo models of BTKi-resistant MCL and CLL is currently ongoing. Altogether these data provide a rationale for evaluating PRT2527 in combination with BTK and BCL2 inhibitors for the treatment of patients with relapsed/refractory hematologic malignancies.
    Combination therapy
    |
    MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CDK9 (Cyclin Dependent Kinase 9) • BMF (Bcl2 Modifying Factor)
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • PRT2527
    8ms
    A phase 1 dose-escalation study of PRT2527, a cyclin-dependent kinase 9 (CDK9) inhibitor, in adult patients with advanced solid tumors: an updated analysis. (AACR-NCI-EORTC 2023)
    No abstract available
    Clinical • P1 data • Metastases
    |
    CDK9 (Cyclin Dependent Kinase 9)
    |
    PRT2527
    9ms
    A phase 1 study evaluating PRT2527, a potent and highly selective CDK9 inhibitor, in patients with select relapsed/refractory B-cell malignancies (IWCLL 2023)
    Secondary endpoints include objective response rate, duration of response, duration of complete response, and pharmacokinetic profile of PRT2527. The study is open to enrollment and registered at ClinicalTrials.gov, NCT05665530.
    Clinical • P1 data
    |
    CASP3 (Caspase 3)
    |
    PRT2527
    9ms
    A Study of PRT2527 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=30, Active, not recruiting, Prelude Therapeutics | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2023 --> Oct 2023
    Enrollment closed • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    HR positive • HER-2 negative • MYC amplification
    |
    PRT2527
    1year
    A phase 1, open-label, multicenter, dose-escalation study of PRT2527, a cyclin-dependent kinase 9 (CDK9) inhibitor, in adult patients (pts) with advanced solid tumors (AACR 2023)
    PRT2527 is generally well tolerated in adults with advanced solid tumors. Updated data (including efficacy) will be presented.
    Clinical • P1 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDK9 (Cyclin Dependent Kinase 9)
    |
    HER-2 amplification • HER-2 negative • MYC amplification • MYC expression
    |
    PRT2527
    over1year
    A Study of PRT2527 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=30, Recruiting, Prelude Therapeutics | Trial primary completion date: Dec 2022 --> Jul 2023
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    HR positive • HER-2 negative • MYC amplification
    |
    PRT2527
    over1year
    PRT2527, a Novel Highly Selective Cyclin-Dependent Kinase 9 (CDK9) Inhibitor, Has Potent Anti-Leukemic Activity in Preclinical Primary Models of Human B-ALL, T-ALL, and CLL (ASH 2022)
    Doxorubicin, Ibrutinib and Venetoclax served as positive control therapeutic agents to assess the responsiveness of primary cultures ex vivo...Notably, the two less responsive models were from CLL patients who responded to Rituximab/Ibrutinib SoC therapy without further disease progression...These data and those reported previously support the advancement of PRT2527 into clinical studies in leukemia patients, especially in patients refractory or progressing on standard therapies. PRT2527 is currently in phase 1 studies in solid tumor patients.
    Preclinical
    |
    CD19 (CD19 Molecule) • KMT2A (Lysine Methyltransferase 2A) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • PRAME (Preferentially Expressed Antigen In Melanoma) • CDK9 (Cyclin Dependent Kinase 9) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
    |
    KMT2A rearrangement • MLL rearrangement • MLL rearrangement
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Rituxan (rituximab) • doxorubicin hydrochloride • PRT2527
    almost2years
    A Study of PRT2527 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=30, Recruiting, Prelude Therapeutics | N=100 --> 30
    Enrollment change
    |
    HER-2 (Human epidermal growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    HER-2 negative • MYC amplification
    |
    PRT2527
    2years
    PRT2527, a novel highly selective cyclin-dependent kinase 9 (CDK9) inhibitor, is active in preclinical models of prostate cancer (AACR 2022)
    Collectively, our data demonstrate that PRT2527 has potent pharmacodynamic and antitumor activity in multiple models of castration-sensitive and castration-resistant prostate cancer. PRT2527 is advancing into phase 1 studies in solid tumors.
    Preclinical
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • SOX2 • CDK9 (Cyclin Dependent Kinase 9)
    |
    MYC expression
    |
    PRT2527
    over2years
    A Study of PRT2527 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=100, Recruiting, Prelude Therapeutics | Not yet recruiting --> Recruiting
    Enrollment open
    |
    ER (Estrogen receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    ER positive
    |
    PRT2527
    over2years
    A Study of PRT2527 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=100, Not yet recruiting, Prelude Therapeutics
    New P1 trial
    |
    ER (Estrogen receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    ER positive
    |
    PRT2527
    over2years
    [VIRTUAL] PRT2527 is a potent and selective CDK9 inhibitor that demonstrates anti-cancer activity in preclinical models of hematological malignancies and solid tumors with MYC amplification (AACR-NCI-EORTC 2021)
    No abstract available
    Preclinical
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog)
    |
    MYC amplification
    |
    PRT2527