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    DRUG:

    JNJ-8177

    i
    Other names: JNJ-8177, JNJ-95298177, ARX517, ARX517-PSMA-ADC, ARX 517, ARX-517, JNJ8177, JNJ 8177, JNJ95298177, JNJ 95298177
    Company:
    J&J
    Drug class:
    Tubulin inhibitor, PSMA-targeted antibody-drug conjugate
    Related drugs:
    3ms
    Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban)
    Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 (dual PSMA/STEAP1-targeted), and DXC008 (dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, the B7-H3-targeted ADC ifinatamab deruxtecan has initiated an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC in May 2025. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of this highly lethal disease.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • STEAP1 (STEAP Family Member 1) • SLC44A4 (Solute Carrier Family 44 Member 4) • SLC4A4 (Solute carrier family 4 member 4)
    |
    Aidixi (disitamab vedotin) • Trodelvy (sacituzumab govitecan-hziy) • ifinatamab deruxtecan (DS-7300) • vobramitamab duocarmazine (MGC018) • ASG 5ME • JNJ-8177 • BNT324 • MEDI3726 • Tivdak (tisotumab vedotin-tftv) • vandortuzumab vedotin (RG7450)
    4ms
    A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer (clinicaltrials.gov)
    P1, N=110, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    JNJ-8177 • pasritamig (JNJ-8343)
    4ms
    A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer (clinicaltrials.gov)
    P1, N=110, Not yet recruiting, Janssen Research & Development, LLC
    New P1 trial
    |
    JNJ-8177 • pasritamig (JNJ-8343)
    5ms
    APEX-01: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1, N=253, Recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2026 --> Dec 2028 | Trial primary completion date: May 2026 --> Jun 2027
    Trial completion date • Trial primary completion date
    |
    abiraterone acetate • prednisone • apalutamide • JNJ-8177
    8ms
    APEX-01: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1, N=253, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2028 --> Sep 2026
    Trial completion date
    |
    abiraterone acetate • prednisone • apalutamide • JNJ-8177
    1year
    APEX-01: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1, N=352, Recruiting, Ambrx, Inc. | N=262 --> 352 | Trial completion date: Mar 2027 --> Dec 2028 | Trial primary completion date: Dec 2025 --> May 2026
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    FOLH1 (Folate hydrolase 1)
    |
    FOLH1 expression
    |
    abiraterone acetate • prednisone • apalutamide • JNJ-8177
    over1year
    APEX-01: ARX517 in Subjects With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov)
    P1, N=262, Recruiting, Ambrx, Inc. | Phase classification: P1/2 --> P1
    Phase classification • Metastases
    |
    FOLH1 (Folate hydrolase 1)
    |
    FOLH1 expression
    |
    JNJ-8177
    almost2years
    APEX-01: ARX517 as Monotherapy and in Combination Regimens in Subjects With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=222, Recruiting, Ambrx, Inc.
    Trial completion date • Trial primary completion date • Metastases
    |
    FOLH1 (Folate hydrolase 1)
    |
    FOLH1 expression
    |
    Xtandi (enzalutamide) • JNJ-8177
    2years
    APEX-01: ARX517 as Monotherapy and in Combination Regimens in Subjects With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=222, Recruiting, Ambrx, Inc. | N=150 --> 222
    Enrollment change • Metastases
    |
    FOLH1 (Folate hydrolase 1)
    |
    FOLH1 expression
    |
    Xtandi (enzalutamide) • JNJ-8177
    over2years
    ARX517-2011: ARX517 in Subjects With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=150, Recruiting, Ambrx, Inc. | Phase classification: P1 --> P1/2 | N=76 --> 150 | Trial completion date: Aug 2024 --> Mar 2027 | Trial primary completion date: Feb 2024 --> Dec 2025
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    |
    JNJ-8177
    over2years
    Preclinical characterization of ARX517, a next-generation anti-PSMA antibody drug conjugate for the treatment of metastatic castration-resistant prostate cancer (AACR 2023)
    The serum stability of ARX517 should effectively deliver more payload to target tumor cells, and in multiple CDX and PDX prostate cancer models, ARX517 showed dose-dependent anti-tumor activity in both enzalutamide-sensitive and enzalutamide-resistant models. The strong preclinical data and recent clinical validation of PSMA as a mCRPC target provide rationale for evaluation of ARX517 as a potential prostate cancer treatment. ARX517 is currently in a Phase 1 dose escalation trial (ARX517-2011 [NCT04662580]) in the United States.
    Preclinical • Metastases
    |
    FOLH1 (Folate hydrolase 1)
    |
    FOLH1 expression • FOLH1 overexpression
    |
    Xtandi (enzalutamide) • JNJ-8177