^
    4d
    Small-molecule modulators of the androgen receptor N-terminal domain: Advances in medicinal chemistry for prostate cancer. (PubMed, Eur J Med Chem)
    Advances in screening platforms and the optimization of structure-activity relationships are beginning to address the challenges of targeting disordered protein domains. With agents like EPI-7386 entering clinical evaluation and others advancing through preclinical development, AR NTD-targeted therapies represent a promising avenue to overcome resistance in castration-resistant prostate cancer (CRPC), potentially in combination with existing LBD-directed treatments to achieve more durable disease control.
    Review • Journal
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    AR (Androgen receptor)
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    AR splice variant 7
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    masofaniten (EPI-7386)
    11ms
    EPI-7386-CS-010: EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC (clinicaltrials.gov)
    P1/2, N=77, Terminated, ESSA Pharmaceuticals | N=150 --> 77 | Active, not recruiting --> Terminated; Study was terminated early due to a lack of improved efficacy.
    Enrollment change • Trial termination
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    Xtandi (enzalutamide) • masofaniten (EPI-7386)
    11ms
    EPI-7386-CS-001: Oral EPI-7386 in Patients with Castration-Resistant Prostate Cancer (clinicaltrials.gov)
    P1, N=71, Terminated, ESSA Pharmaceuticals | Active, not recruiting --> Terminated; Study was terminated early due to a lack of improved efficacy.
    Trial termination
    |
    abiraterone acetate • apalutamide • masofaniten (EPI-7386)
    12ms
    A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov)
    P1, N=3, Terminated, Janssen Research & Development, LLC | Phase classification: P1b --> P1
    Phase classification
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    abiraterone acetate • prednisone • apalutamide • masofaniten (EPI-7386)
    1year
    EPI-7386-CS-010: EPI-7386 in Combination with Enzalutamide Compared with Enzalutamide Alone in Subjects with MCRPC (clinicaltrials.gov)
    P1/2, N=150, Active, not recruiting, ESSA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jan 2025 | Trial primary completion date: Aug 2025 --> Oct 2024
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    Xtandi (enzalutamide) • masofaniten (EPI-7386)
    1year
    EPI-7386-CS-001: Oral EPI-7386 in Patients with Castration-Resistant Prostate Cancer (clinicaltrials.gov)
    P1, N=99, Active, not recruiting, ESSA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Sep 2026 --> Jan 2025 | Trial primary completion date: Apr 2026 --> Oct 2024
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    abiraterone acetate • apalutamide • masofaniten (EPI-7386)
    almost2years
    Combining EPI-7386 w/ Enzalutamide & Androgen Deprivation Therapy for Newly Diagnosed Prostate Cancer (clinicaltrials.gov)
    P2, N=35, Not yet recruiting, Pedro Barata, MD, MSc
    New P2 trial • Metastases
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    Xtandi (enzalutamide) • masofaniten (EPI-7386)
    2years
    EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC (clinicaltrials.gov)
    P1/2, N=150, Recruiting, ESSA Pharmaceuticals
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    Xtandi (enzalutamide) • masofaniten (EPI-7386)
    over2years
    Phase I/II trial of oral EPI-7386 in combination with enzalutamide (enz) compared to enz alone in metastatic castration-resistant prostate cancer (mCRPC) subjects: Current phase I (PI) results (ESMO 2023)
    Conclusions With no safety concerns from cohorts 1-3, cohort 4 is currently enrolling at EPI-7386 BID + 160 mg QD Enz to evaluate optimal RP2Ds before the P2 component of the trial. Updated results, including cohort 4, will be presented.
    Clinical • P1/2 data • Combination therapy • Metastases
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    CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    Xtandi (enzalutamide) • masofaniten (EPI-7386)
    over2years
    A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov)
    P1b, N=3, Terminated, Janssen Research & Development, LLC | N=82 --> 3 | Trial completion date: Jun 2025 --> Sep 2022 | Suspended --> Terminated | Trial primary completion date: Jan 2024 --> Sep 2022; Administrative Decision
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
    |
    abiraterone acetate • prednisone • apalutamide • masofaniten (EPI-7386)