Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy

Официальное название

PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy

Обзор

This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment

Подробное описание

Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.

Вмешательства

• Препарат Investigators choice of SoC
  The control treatment in Phase III is investigator's choice of SoC
• Препарат AAA817
  The investigational treatment is AAA817
• Препарат AAA817
  The investigational treatment is AAA817
• Препарат AAA817
  Investigational treatment is the Dose B of AAA817

Первичные конечные точки

• Biochemical response rate (Phase II) [Срок оценки: from date of randomization up to approximately 24 months]
• Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II [Срок оценки: from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later]
• Tolerability of the proposed dose of AAA817- Phase II [Срок оценки: From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817]
• Radiographic progression-free survival (rPFS)- Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• Overall survival (OS)- Phase III [Срок оценки: from date of randomization up to approximately 24 months]

Вторичные конечные точки (12)

• Radiographic progression-free survival (rPFS)- Phase II [Срок оценки: from date of randomization up to approximately 24 months]
• Progression free survival (PFS)- Phase II [Срок оценки: from date of randomization up to approximately 24 months]
• Overall response rate (ORR)- Phase II [Срок оценки: from date of randomization up to approximately 24 months]
• Disease control rate (DCR)- Phase II [Срок оценки: from date of randomization up to approximately 24 months]
• Overall survival (OS)- Phase II [Срок оценки: from date of randomization up to approximately 24 months]
• Progression free survival (PFS) -Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• Overall response rate (ORR)- Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• Disease control rate (DCR) -Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• Duration of response (DoR)- Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• Time to first radiographic soft tissue progression (TTSTP)- Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• First symptomatic skeletal event (TTSSE)_Phase III [Срок оценки: from date of randomization up to approximately 24 months]
• Prostate specific antigen (PSA) response -Phase III [Срок оценки: from date of randomization up to approximately 24 months]

Критерии участия

Inclusion Criteria: ∙

• adults ≥ 18 years of age.
• ECOG performance status of 0 to 2.
• histopathological and/or cytological confirmation of adenocarcinoma of the prostate.
• PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed,
• castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
• Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy.
• ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
• eGFR as requested by the sponsor

Критерии исключения

• Any investigational agents within 28 days prior to the day of randomization.
• Any 225Ac-based investigational compound used prior to the day of randomization.
• Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
• Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury)
• Baseline xerostomia ≥ Grade 2 by CTCAE v.5
• History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
• History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed).

Other protocol-defined 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 · 27 центров

• VA Greater LA Healthcare System — Los Angeles
• VA Palo Alto Health Care System — Palo Alto
• Stanford University Medical Center — Palo Alto
• Sansum Clinic — Santa Barbara
• Saint Johns Cancer Institute — Santa Monica
• Hartford Hospital — Hartford
• AdventHealth — Orlando
• University Cancer and Blood Center LLC — Athens
• … и ещё 19 центров

Китай · 15 центров

• Novartis Investigative Site — Фучжоу
• Novartis Investigative Site — Ухань
• Novartis Investigative Site — Ухань
• Novartis Investigative Site — Нанкин
• Novartis Investigative Site — Нанкин
• Novartis Investigative Site — Шэньян
• Novartis Investigative Site — Сиань
• Novartis Investigative Site — Сиань
• … и ещё 7 центров

Япония · 11 центров

• Novartis Investigative Site — Kashiwa
• Novartis Investigative Site — Sapporo
• Novartis Investigative Site — Kobe
• Novartis Investigative Site — Yokohama
• Novartis Investigative Site — Chiba
• Novartis Investigative Site — Fukuoka
• Novartis Investigative Site — Fukuoka
• Novartis Investigative Site — Fukuoka
• … и ещё 3 центра

Израиль · 6 центров

• Novartis Investigative Site — Beersheba
• Novartis Investigative Site — Haifa
• Novartis Investigative Site — Jerusalem
• Novartis Investigative Site — Petah Tikva
• Novartis Investigative Site — Ramat Gan
• Novartis Investigative Site — Tel Aviv

South Korea · 4 центра

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

Тайвань · 4 центра

• Novartis Investigative Site — Taipei
• Novartis Investigative Site — Taipei
• Novartis Investigative Site — Taipei
• … и ещё 1 центр

Австралия · 3 центра

• Novartis Investigative Site — Darlinghurst
• Novartis Investigative Site — Herston
• Novartis Investigative Site — Melbourne

Сингапур · 3 центра

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

Швейцария · 3 центра

• Novartis Investigative Site — Basel
• Novartis Investigative Site — Bellinzona
• Novartis Investigative Site — Bern

Бразилия · 2 центра

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

Малайзия · 2 центра

• Novartis Investigative Site — Petaling Jaya
• Novartis Investigative Site — Petaling Jaya

Гонконг · 1 центр

• Novartis Investigative Site — Гонконг

Идентификаторы

NCT: NCT06780670 · CAAA817A12201 · 2024-512342-42-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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