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

Official title

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)

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

• Number of participants with dose-limiting toxicity (DLT), as defined in the protocol (Part A only) [Time frame: From first dose of study intervention to 28 days post first dose]
• Number of participants with Adverse Events and Serious Adverse Events [Time frame: 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 [Time frame: 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. [Time frame: From first study dose up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in physical examination. [Time frame: 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. [Time frame: From first dose of study intervention up to 37 days after the last dose of study treatment]
• Clinically significant changes from baseline in ECGs. [Time frame: 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. [Time frame: 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) [Time frame: From first dose of study intervention up to 14 days after the last dose of study treatment]

Secondary outcome measures (12)

• Proportion of participants achieving a ≥ 50% decrease in PSA from baseline (PSA50) (Part A only) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: From randomisation or first dose of study intervention to progression, assessed up to 60 months]
• Best percentage change in target lesion size from baseline [Time frame: 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) [Time frame: 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 [Time frame: From date of first dose of study intervention up to 115 days after first dose]
• tmax of AZD9750 [Time frame: From date of first dose of study intervention up to 115 days after first dose]
• AUC of AZD9750 [Time frame: From date of first dose of study intervention up to 115 days after first dose]
• Cmax of saruparib (Module 2 only) [Time frame: From date of first dose of study intervention up to 57 days after first dose]

Eligibility criteria

• 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.

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

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• 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

Canada · 2 centers

• Research Site — Calgary
• Research Site — Vancouver

Japan · 2 centers

• Research Site — Chūōku
• Research Site — Kashiwa

Netherlands · 2 centers

• Research Site — Amsterdam
• Research Site — Rotterdam

Australia · 1 center

• Research Site — Melbourne

China · 1 center

• Research Site — Chengdu

Spain · 1 center

• Research Site — Barcelona

United Kingdom · 1 center

• Research Site — Cambridge

Identifiers

NCT: NCT07336446 · D7270C00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗