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

Official title

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)

Overview

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.

Interventions

• Drug JSB462
  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.
• Drug Abiraterone
  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.
• Drug Enzalutamide
  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.

Primary outcome measures

• Prostate Specific Antigen 90 (PSA90) Rate [Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]
• Incidence rate of adverse events (AEs) [Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]
• Number of participants with dose adjustments [Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]
• Duration of exposure to study treatment [Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]

Secondary outcome measures (12)

• 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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

Other inclusion/exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 21 centers

• University of California San Diego - Moores Cancer Center — La Jolla
• Saint Johns Cancer Institute — Santa Monica
• Rocky Mountain Cancer Centers — Denver
• Yale Cancer Center — New Haven
• Advanced Urology Ins Daytona Beach — Daytona Beach
• Emory University School of Medicine-Winship Cancer Institute — Atlanta
• Associated Urological Specialists — Chicago Ridge
• American Oncology Partners PA Center for Cancer and Blood Disorders — Bethesda
• … and 13 more centers

Spain · 6 centers

• Novartis Investigative Site — Santander
• Novartis Investigative Site — Badajoz
• Novartis Investigative Site — Lugo
• Novartis Investigative Site — Pamplona
• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Córdoba

Italy · 5 centers

• Novartis Investigative Site — Asti
• Novartis Investigative Site — Padova
• Novartis Investigative Site — Trento
• Novartis Investigative Site — Orbassano
• Novartis Investigative Site — Verona

France · 4 centers

• Novartis Investigative Site — Nice
• Novartis Investigative Site — Marseille
• Novartis Investigative Site — Quint-Fonsegrives
• Novartis Investigative Site — Suresnes

Germany · 4 centers

• Novartis Investigative Site — Düsseldorf
• Novartis Investigative Site — Hamburg
• Novartis Investigative Site — Lübeck
• Novartis Investigative Site — Nürtingen

Netherlands · 4 centers

• Novartis Investigative Site — Zwolle
• Novartis Investigative Site — Dordrecht
• Novartis Investigative Site — Hoofddorp
• Novartis Investigative Site — Schiedam

Poland · 4 centers

• Novartis Investigative Site — Kielce
• Novartis Investigative Site — Olsztyn
• Novartis Investigative Site — Oświęcim
• Novartis Investigative Site — Skorzewo

Canada · 3 centers

• Novartis Investigative Site — Vancouver
• Novartis Investigative Site — Halifax
• Novartis Investigative Site — Montreal

Czechia · 3 centers

• Novartis Investigative Site — Brno
• Novartis Investigative Site — Olomouc
• Novartis Investigative Site — Prague

Singapore · 3 centers

• Novartis Investigative Site — Singapore
• Novartis Investigative Site — Singapore
• Novartis Investigative Site — Singapore

Australia · 2 centers

• Novartis Investigative Site — Adelaide
• Novartis Investigative Site — Clayton

Brazil · 2 centers

• Novartis Investigative Site — Fortaleza
• Novartis Investigative Site — São Paulo

China · 2 centers

• Novartis Investigative Site — Beijing
• Novartis Investigative Site — Beijing

South Korea · 2 centers

• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Seoul

Taiwan · 2 centers

• Novartis Investigative Site — Kaohsiung City
• Novartis Investigative Site — Tainan

Identifiers

NCT: NCT06991556 · CJSB462C12201 · 2024-520156-22-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗