A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
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
Detailed description
The study for each participant consists of a Screening period (28 days), a treatment period, a post-treatment safety follow-up (30 days) followed by a long-term follow-up period. During the treatment period: * JSB462 is administered from randomization, 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. * Abiraterone 1000 mg or enzalutamide 160 mg are administered from randomization, 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. During the post-treatment follow up period: * Safety follow-Up: After discontinuation of study treatment, all participants will be followed for at least 1 safety follow-up visit (30 days \[+/- 7 days\] after treatment discontinuation). Subsequent lines of therapy may be administered according to investigator's discretion after treatment discontinuation. * Long-term follow-up: Starts after the Safety follow-up period and lasts until the end of study. Safety, efficacy and survival information may be collected from participants during this period.
Arms & interventions
- DrugJSB462
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.
- DrugAbiraterone
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.
- DrugEnzalutamide
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.
Outcome measures
Primary
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
Secondary
Radiographic Progression Free Survival (rPFS)
Time frame: 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)
Time frame: From date of randomization until date of death from any cause, assessed up to approximately 83 months
Incidence rate of adverse events (AEs)
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 83 months
Overall Response Rate (ORR)
Time frame: 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)
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months
Duration of Response (DOR)
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months
Time to Response (TTR)
Time frame: From date of randomization until date of first documented Complete Response (CR) or Partial Response (PR), assessed up to approximately 83 months
Time to soft tissue progression (TTSTP)
Time frame: From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 83 months
Prostate Specific Antigen 30 (PSA30) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
Prostate Specific Antigen 50 (PSA50) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
Prostate Specific Antigen 0 (PSA0) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months
Duration of biochemical response (DBR)
Time frame: From date of date of first PSA50 response until date of PSA progression or death from any cause, assessed up to approximately 83 months
Time to first symptomatic skeletal event (TTSSE)
Time frame: From date of randomization till EOT or death, whichever happens first, assessed up to approximately 83 months
Plasma concentrations of JSB462 and plasma concentrations of its metabolite ARV-767
Time frame: Day 1 of Cycles 1 and 2: Pre-dose/0h and Post-dose 4h +/- 1h. Day 1 of Cycles 3 to 8: Pre-dose/0h. End of Treatment Visit (EOT): Anytime. 1 cycle = 28 days.
Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time frame: From randomization up till 30 day safety Follow-up, assessed up to approximately 83 months
Eligibility criteria
Study locations (21)
University of California San Diego - Moores Cancer Center
La Jolla, California, 92093-0658
Saint Johns Cancer Institute
Santa Monica, California, 90404
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Yale Cancer Center
New Haven, Connecticut, 06520
Advanced Urology Ins Daytona Beach
Daytona Beach, Florida, 32114
Emory University School of Medicine-Winship Cancer Institute
Atlanta, Georgia, 30322
Associated Urological Specialists
Chicago Ridge, Illinois, 60415
American Oncology Partners PA Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Mass General Hospital
Boston, Massachusetts, 02114
Michigan Institute of Urology
West Bloomfield, Michigan, 48322
XCancer Omaha LLC
Omaha, Nebraska, 68130
Perlmutter Cancer Centre
New York, New York, 10016
Associated Med Professionals of NY
Syracuse, New York, 13210
Montefiore Medical Center
The Bronx, New York, 10467
MidLantic Urology
Bala-Cynwyd, Pennsylvania, 19004
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Tennessee Oncology
Nashville, Tennessee, 37203
Urology San Antonio
San Antonio, Texas, 78229
Virginia Oncology Associates
Norfolk, Virginia, 23502
Fred Hutch Cancer Research
Seattle, Washington, 98109