ANDROMEDA: Targeted androgen-receptor directed therapy with AZD9750 alone or in combination with saruparib in people with metastatic prostate cancerA 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)

Inclusion

• 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:

  1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination.
  2. Radiographic progression of soft tissue disease by RECIST v1.1 with or without PSA progression.
  3. 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.