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.
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.
Eligibility
- 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.
