An Open-label Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

NCT06991556 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CJSB462C122012024-520156-22-00
• Study Type: interventional
• Target: 150
• Locations: 15 countries
• Sites: 65

Brief Summary

This Phase II study aims to evaluate efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg once a day (QD) doses + abiraterone compared with an androgen receptor pathway inhibitor (ARPI, abiraterone or enzalutamide) in participants with metastatic Hormone Sensitive Prostate Cancer (mHSPC) and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and PK data from participants randomized in the study will be evaluated

Conditions

Metastatic Hormone-sensitive Prostate Cancer

Keywords

Interventional; clinical trial; open-label; JSB462; luxdegalutamide; efficacy; safety; tolerability; abiraterone; metastatic hormone-sensitive prostate cancer

Outcome Measures

Primary Outcomes (4)

• Prostate Specific Antigen 90 (PSA90) Rate

  Prostate Specific Antigen 90 (PSA90) Rate is defined as the proportion of participants who achieve a ≥90% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between.

  From date of randomization till 30 days safety fup, assessed up to approximately 75 months

• Incidence rate of adverse events (AEs)

  The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.

  From date of randomization till 30 days safety fup, assessed up to approximately 75 months

• Number of participants with dose adjustments

  The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.

  From date of randomization till 30 days safety fup, assessed up to approximately 75 months

• Duration of exposure to study treatment

  The duration of exposure in weeks to study treatment and for each study treatment component (JSB462, abiraterone and enzalutamide) will be summarized for each study treatment component by means of descriptive statistics using the SAS.

  From date of randomization till 30 days safety fup, assessed up to approximately 75 months

Secondary Outcomes (15)

• Radiographic Progression Free Survival (rPFS)

  From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 83 months

• Overall Survival (OS)

  From date of randomization until date of death from any cause, assessed up to approximately 83 months

• Incidence rate of adverse events (AEs)

  From date of randomization till 30 days safety fup, assessed up to approximately 83 months

• Overall Response Rate (ORR)

  From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months

• Disease Control Rate (DCR)

  From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months

Study Arms (3)

Arm 1

EXPERIMENTAL

JSB462 100 mg QD + abiraterone 1000 mg QD

Drug: JSB462; Drug: Abiraterone

Arm 2

EXPERIMENTAL

JSB462 300 mg QD + abiraterone 1000 mg QD

Drug: JSB462; Drug: Abiraterone

Arm 3

ACTIVE COMPARATOR

abiraterone 1000 mg QD or enzalutamide 160 mg QD

Drug: Abiraterone; Drug: Enzalutamide

Interventions

JSB462 DRUG

JSB462 is administered orally, daily and continuously (100 mg or 300 mg QD) until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.

Also known as: luxdegalutamide

Arm 1; Arm 2

Abiraterone DRUG

Abiraterone 1000 mg is administered orally, daily and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.

Arm 1; Arm 2; Arm 3

Enzalutamide DRUG

Enzalutamide 160 mg is administered orally, daily and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.

Arm 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2
• Histologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible
• High-volume mHSPC, defined by the presence of ≥1 metastatic visceral non-nodal lesion and/or ≥4 metastatic bone lesions (with at least one lesion outside the vertebral column and/or pelvis) in imaging exams (CT/MRI or bone scan) according to local radiology assessment by the investigator obtained ≤28 days prior to randomization
• Participants must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L). Ongoing ADT (as defined by prior orchiectomy and/or ongoing GnRH analog/antagonist) for ≤90 days is allowed prior to randomization, provided that PSA zero (PSA level \<0.2 ng/ml according to local laboratory as assessed by the investigator) is not achieved prior to randomization.

You may not qualify if:

• Prior exposure to a second generation ARPI (such as enzalutamide/darolutamide/apalutamide and/or abiraterone) for the treatment of advanced/metastatic disease is not allowed. Prior exposure to ARPI, to taxane chemotherapy (up to 6 cycles) or to RLT in the context of (neo)adjuvant treatment for localized prostate cancer is allowed, if the last dose of this treatment was administered \>12 months from randomization. Prior use of a first generation ARPI (such as bicalutamide) in the context of ADT initiation with a GnRH analog is allowed, provided the first generation ARPI was administered for ≤14 days and last dose was administered ≥7 days from randomization.
• Participants with biochemical recurrence only or those without evidence of metastatic disease by radiological imaging (CT/MRI or bone scan) are not eligible

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (65)

University of California San Diego - Moores Cancer Center

La Jolla, California, 92093-0658, United States

RECRUITING

Saint Johns Cancer Institute

Santa Monica, California, 90404, United States

RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Advanced Urology Ins Daytona Beach

Daytona Beach, Florida, 32114, United States

RECRUITING

Emory University School of Medicine-Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Associated Urological Specialists

Chicago Ridge, Illinois, 60415, United States

RECRUITING

American Oncology Partners PA Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

RECRUITING

Mass General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Michigan Institute of Urology

West Bloomfield, Michigan, 48322, United States

RECRUITING

XCancer Omaha LLC

Omaha, Nebraska, 68130, United States

RECRUITING

Perlmutter Cancer Centre

New York, New York, 10016, United States

RECRUITING

Associated Med Professionals of NY

Syracuse, New York, 13210, United States

RECRUITING

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Urology San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Fred Hutch Cancer Research

Seattle, Washington, 98109, United States

RECRUITING

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

RECRUITING

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, 01221-020, Brazil

RECRUITING

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Novartis Investigative Site

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Novartis Investigative Site

Beijing, Chaoyang, 100021, China

RECRUITING

Novartis Investigative Site

Beijing, 100034, China

RECRUITING

Novartis Investigative Site

Brno, 656 53, Czechia

RECRUITING

Novartis Investigative Site

Olomouc, 779 00, Czechia

RECRUITING

Novartis Investigative Site

Prague, 150 06, Czechia

RECRUITING

Novartis Investigative Site

Nice, Alpes Maritimes, 06189, France

RECRUITING

Novartis Investigative Site

Marseille, 13273, France

RECRUITING

Novartis Investigative Site

Quint-Fonsegrives, 31130, France

RECRUITING

Novartis Investigative Site

Suresnes, 92150, France

RECRUITING

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Novartis Investigative Site

Hamburg, 20246, Germany

RECRUITING

Novartis Investigative Site

Lübeck, 23538, Germany

RECRUITING

Novartis Investigative Site

Nürtingen, 72622, Germany

RECRUITING

Novartis Investigative Site

Asti, AT, 14100, Italy

RECRUITING

Novartis Investigative Site

Padova, PD, 35128, Italy

RECRUITING

Novartis Investigative Site

Trento, TN, 38122, Italy

RECRUITING

Novartis Investigative Site

Orbassano, TO, 10043, Italy

RECRUITING

Novartis Investigative Site

Verona, VR, 37134, Italy

RECRUITING

Novartis Investigative Site

Zwolle, Overijssel, 8025 AB, Netherlands

RECRUITING

Novartis Investigative Site

Dordrecht, South Holland, 3318 AT, Netherlands

RECRUITING

Novartis Investigative Site

Hoofddorp, 2134 TM, Netherlands

RECRUITING

Novartis Investigative Site

Schiedam, 3118 JH, Netherlands

RECRUITING

Novartis Investigative Site

Kielce, 25-640, Poland

RECRUITING

Novartis Investigative Site

Olsztyn, 10-288, Poland

RECRUITING

Novartis Investigative Site

Oświęcim, 32-600, Poland

RECRUITING

Novartis Investigative Site

Skorzewo, 60-185, Poland

RECRUITING

Novartis Investigative Site

Singapore, 119074, Singapore

RECRUITING

Novartis Investigative Site

Singapore, 169608, Singapore

RECRUITING

Novartis Investigative Site

Singapore, S308433, Singapore

RECRUITING

Novartis Investigative Site

Seoul, 03080, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 06351, South Korea

RECRUITING

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

RECRUITING

Novartis Investigative Site

Badajoz, Extremadura, 06080, Spain

RECRUITING

Novartis Investigative Site

Lugo, Galicia, 27003, Spain

RECRUITING

Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08036, Spain

RECRUITING

Novartis Investigative Site

Córdoba, 14004, Spain

RECRUITING

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

RECRUITING

Novartis Investigative Site

Tainan, 704302, Taiwan

RECRUITING

MeSH Terms

Interventions

abiraterone; enzalutamide

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 28, 2025
• Study Start: July 7, 2025
• Primary Completion (Estimated): March 29, 2032
• Study Completion (Estimated): October 19, 2035
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (4); FR (4); IT (5); US (20); AU (2); PL (4); TW (2); KR (2); BR (1); CA (3); SG (3); CN (2); CZ (3); NL (4); ES (6)