A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer Drugs

Официальное название

A Phase I/II, Modular, Open-Label, Multi-Centre Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD9750 as Monotherapy and in Combination With Other Anticancer Agents in Participants With Metastatic Prostate Cancer (ANDROMEDA)

Обзор

ANDROMEDA is a first-in-human, Phase I/II, open-label, multicenter study of AZD9750 in participants with metastatic prostate cancer. The trial evaluates safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of AZD9750 as monotherapy and in combination with saruparib.

Подробное описание

This first-in-human (FiH), Phase I/II, open-label, multicenter study will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AZD9750 as monotherapy and in combination with saruparib in participants with metastatic prostate cancer. Additional combinations with other anticancer agents may be added via protocol amendment as separate modules. The study follows a modular design, allowing initial assessment of safety, tolerability, and preliminary efficacy across multiple treatment arms. Each Module has 2 parts: Part A (monotherapy dose escalation or combination dose finding) and Part B (monotherapy dose optimization and expansion or combination dose expansion). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention occur.

Вмешательства

• Препарат AZD9750
  AR-PROTAC
• Препарат AZD5305
  PARP1-selective inhibitor

Первичные конечные точки

• Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only) [Срок оценки: From first dose of study intervention to 28 days post first dose]
• Number of participants with Adverse Events and Serious Adverse Events [Срок оценки: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Number of participants with Adverse Events leading to discontinuation of study intervention [Срок оценки: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in vital signs. [Срок оценки: From first study dose up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in physical examination. [Срок оценки: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in ECOG PS. [Срок оценки: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in ECGs. [Срок оценки: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in laboratory parameters. [Срок оценки: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Proportion of participants achieving a ≥50% decrease in PSA from baseline (PSA50) (Part B only) [Срок оценки: From first dose of study intervention up to 14 days after the last dose of study treatment]

Вторичные конечные точки (12)

• Proportion of participants achieving a ≥ 50% decrease in PSA from baseline (PSA50) (Part A only) [Срок оценки: From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment]
• Proportion of participants achieving a ≥ 90% decrease in PSA from baseline (PSA90) [Срок оценки: From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment]
• Objective response rate (ORR) [Срок оценки: From randomisation or first dose of study intervention to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months]
• Duration of response (DoR) [Срок оценки: From randomisation or first dose of study intervention to the date of first documented radiological disease progression, assessed up to 60 months]
• Time to response (TTR) [Срок оценки: From randomisation or first dose of study intervention to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months]
• Radiographic progression-free survival (rPFS) [Срок оценки: From randomisation or first dose of study intervention to progression, assessed up to 60 months]
• Best percentage change in target lesion size from baseline [Срок оценки: From screening (Day -28) to initiation of subsequent anticancer treatment (or radiotherapy on target lesions) or progression, assessed up to 60 months]
• Time to PSA response (TTPSA50, TTPSA90) [Срок оценки: From first dose of study intervention up to initiation of subsequent anticancer therapy (or radiotherapy on target lesions), PSA progression or 14 days after the last dose of study treatment]
• Cmax of AZD9750 [Срок оценки: From date of first dose of study intervention up to 115 days after first dose]
• tmax of AZD9750 [Срок оценки: From date of first dose of study intervention up to 115 days after first dose]
• AUC of AZD9750 [Срок оценки: From date of first dose of study intervention up to 115 days after first dose]
• Cmax of saruparib (Module 2 only) [Срок оценки: From date of first dose of study intervention up to 57 days after first dose]

Критерии участия

• Inclusion Criteria:

• Participant must be ≥18 years or the legal age at the time of signing the informed consent form.
• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
• Documented metastatic disease.
• Serum testosterone levels ≤ 50 ng/dL.
• Evidence of disease progression with one of the following:

• PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination.
• Radiographic progression of soft tissue disease by RECIST v1.1 with or without PSA progression.
• Radiographic progression of bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
• ECOG performance status score of 0 or 1.
• Adequate bone marrow and organ function.
• Part A (Module 1)

• (a) Part A1 dose escalation: at least 1 prior ARPI and, if applicable, at least 1 taxane-based chemotherapy (regardless of whether in HSPC or CRPC setting).
• (b) Part A2 backfill: at least 1 but no more than 2 prior ARPIs and, if applicable, at least 1 but no more than 2 prior taxane-based chemotherapies (regardless of whether in HSPC or CRPC setting).
• Part B (Module 1)

• (a) B1/B2 dose optimization/expansion: at least 1 but no more than 2 prior ARPIs and, if applicable, at least 1 but no more than 2 prior taxane-based chemotherapies (regardless of whether in HSPC or CRPC setting).
• (b) B3 dose expansion (no taxane cohort): at least 1 but no more than 2 prior ARPIs for metastatic prostate cancer (regardless of whether in HSPC or CRPC setting). No prior taxane is allowed for inclusion in this cohort.
• Exclusion Criteria:

• Participants with pathological finding consistent with any presence of small cell carcinoma, predominant neuroendocrine carcinoma, or any predominant histology other than prostate adenocarcinoma.
• Brain metastases, or spinal cord compression.
• Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
• Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
• Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism of AZD9750 and relevant combination IMPs.
• Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent \[within 6 months\] hemorrhagic stroke, proliferative diabetic retinopathy).
• Prior treatment with an AR-PROTAC.

Other protocol-defined inclusion/exclusion criteria apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• Research Site — Duarte
• Research Site — San Francisco
• Research Site — Tampa
• Research Site — Boston
• Research Site — St Louis
• Research Site — Myrtle Beach
• Research Site — Nashville
• Research Site — Salt Lake City

Канада · 2 центра

• Research Site — Calgary
• Research Site — Vancouver

Япония · 2 центра

• Research Site — Chūōku
• Research Site — Kashiwa

Нидерланды · 2 центра

• Research Site — Amsterdam
• Research Site — Rotterdam

Австралия · 1 центр

• Research Site — Melbourne

Китай · 1 центр

• Research Site — Чэнду

Испания · 1 центр

• Research Site — Barcelona

Великобритания · 1 центр

• Research Site — Cambridge

Идентификаторы

NCT: NCT07336446 · D7270C00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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