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

Официальное название

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)

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Препарат 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.

Первичные конечные точки

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

Вторичные конечные точки (12)

• Radiographic Progression Free Survival (rPFS) [Срок оценки: 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) [Срок оценки: From date of randomization until date of death from any cause, assessed up to approximately 83 months]
• Incidence rate of adverse events (AEs) [Срок оценки: From date of randomization till 30 days safety fup, assessed up to approximately 83 months]
• Overall Response Rate (ORR) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]
• Prostate Specific Antigen 50 (PSA50) Rate [Срок оценки: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]
• Prostate Specific Antigen 0 (PSA0) Rate [Срок оценки: From date of randomization till 30 days safety fup, assessed up to approximately 75 months]
• Duration of biochemical response (DBR) [Срок оценки: From date of date of first PSA50 response until date of PSA progression or death from any cause, assessed up to approximately 83 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 21 центр

• 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
• … и ещё 13 центров

Испания · 6 центров

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

Италия · 5 центров

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

Франция · 4 центра

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

Германия · 4 центра

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

Нидерланды · 4 центра

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

Польша · 4 центра

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

Канада · 3 центра

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

Чехия · 3 центра

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

Сингапур · 3 центра

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

Австралия · 2 центра

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

Бразилия · 2 центра

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

Китай · 2 центра

• Novartis Investigative Site — Пекин
• Novartis Investigative Site — Пекин

South Korea · 2 центра

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

Тайвань · 2 центра

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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