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    DRUG:

    PRT3789

    i
    Other names: PRT3789, PRT-SCA2, PRT-3789, PRT 3789
    Company:
    Prelude Therap
    Drug class:
    SMARCA2 degrader
    Related drugs:
    3d
    A Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, Prelude Therapeutics
    New P2 trial
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation • SMARCA4 deletion
    |
    Keytruda (pembrolizumab) • PRT3789
    5ms
    PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation (clinicaltrials.gov)
    P1, N=186, Recruiting, Prelude Therapeutics | N=118 --> 186
    Enrollment change • Combination therapy • Metastases
    |
    docetaxel • PRT3789
    9ms
    PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation (clinicaltrials.gov)
    P1, N=118, Recruiting, Prelude Therapeutics | N=86 --> 118
    Enrollment change • Combination therapy • Metastases
    |
    docetaxel • PRT3789
    over1year
    A phase I study of PRT3789, a potent and selective degrader of SMARCA2 in patients with advanced or metastatic solid tumors and a SMARCA4 mutation (ESMO 2023)
    Secondary endpoints include objective response rate, progression-free survival, duration of response, disease control rate, and PK and PD profiles of PRT3789. The study began enrolling patients in January 2023.
    Clinical • P1 data • Metastases
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    SMARCA4 mutation
    |
    PRT3789
    almost2years
    A Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation (clinicaltrials.gov)
    P1, N=86, Recruiting, Prelude Therapeutics | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    PRT3789
    almost2years
    A Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation (clinicaltrials.gov)
    P1, N=86, Not yet recruiting, Prelude Therapeutics
    New P1 trial • Metastases
    |
    SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    PRT3789
    over2years
    Preclinical characterization of PRT3789, a potent and selective SMARCA2 targeted degrader (AACR 2022)
    In subcutaneous cell-line derived xenograft (CDX) models of NSCLC, administration of PRT3789 demonstrated significant dose-related inhibition of SMARCA4-deleted NSCLC growth at tolerated doses, but no effect on the growth of SMARCA4 WT cancers. In summary, consistent with our previous validation studies and genomic perturbation analyses, our potent and selective SMARCA2 targeted degrader PRT3789 induces strong synthetic lethality in SMARCA4-deleted cancers in vitro and in vivo.
    Preclinical
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    SMARCA4 mutation • SMARCA4 deletion
    |
    PRT3789
    over2years
    Combination of the MCL1 inhibitor PRT1419 and SMARCA2 degrader PRT3789 shows combinatorial benefit in SMARCA4 deleted lung cancer (AACR 2022)
    In a broader lung cancer cell line viability screen conducted with PRT1419, we observed that the presence of multiple, co-occurring alterations in SWI/SNF family members such as SMARCA4, ARID1A/B mutations and loss of SMARCA2 protein were associated with sensitivity to PRT1419. Based on these findings, preclinical evaluation of PRT1419 in other tumor types with recurrent SWI/SNF mutations is ongoing.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    ARID1A mutation • SMARCA4 mutation • SMARCA4 deletion • MCL1 amplification
    |
    PRT1419 • PRT3789