PARTHENON: Testing a new drug called AZD4956 by itself and with other anti-cancer treatments for people with advanced or metastatic solid cancers with HRR deficienciesA Modular Open-label, Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Ascending Doses of AZD4956 as Monotherapy, and in Combination With Anti-Cancer Agents in Participants With Advanced/Metastatic Homologous Recombination Repair Defective Solid Tumours

Inclusion

Core Inclusion Criteria:

• Documented locally advanced or metastatic solid tumour malignancy.
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to screening and first day of dosing.
• Minimum life expectancy ≥ 12 weeks.
• Adequate organ and marrow function.
• Female participants must not breastfeed and must not donate or retrieve ova for their own use from screening to approximately 6 months after the last dose of study intervention.

Module 1 Inclusion Criteria:

• Demonstrated evidence of disease progression.
• Participants must have advanced or metastatic solid tumours.
• Participants may have received up to one prior line of therapy with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)-based regimen (either as a treatment or as maintenance).

Module 2 Inclusion Criteria:

Part A (AZD4956 in Combination with Saruparib Dose Escalation) and Part A-PD (PD Backfill Cohorts):

• Participants must have one of the following conditions-

  1. Histologically or cytologically confirmed carcinoma of the breast with recurrent locally advanced or metastatic disease and evidence of a predicted loss of function germline or somatic mutation.
  2. Histologically or cytologically confirmed advanced ovarian, fallopian tube, or primary peritoneal cancer.
  3. Histologically or cytologically confirmed adenocarcinoma of the prostate and advanced/metastatic castrate resistant prostate cancer (CRPC).
  4. Histologically or cytologically confirmed advanced/metastatic pancreatic cancer.
• Participants must have evaluable disease.
• Participants in PD backfill cohorts must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).

Part A (PD Backfill Cohorts) - Participants Undergoing Paired Biopsies:

- Participants must have a tumour suitable for biopsy.

Part A-Non-PD (Non-PD Backfill Cohorts) and Part B (Dose Expansion Cohorts):

• Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and advanced/metastatic CRPC.
• Participants must have documented metastatic disease by clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or ≥ 1 soft tissue lesion (measurable or non-measurable).
• Participants must have received the prior approved systemic therapies for metastatic prostate cancer.
• Participants must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).