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 - ANDROMEDA

Inclusion 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:
• (a) PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination.
• (b) Radiographic progression of soft tissue disease by RECIST v1.1 with or without PSA progression.
• (c) 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)
• o (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).
• o (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)
• o (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).
• o (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.