Study of AZD4956 as Monotherapy and in Combination with Anti-Cancer Agents in Participants with Advanced/Metastatic Homologous Recombination Deficient Solid Tumours - PARTHENON

Inclusion Criteria

• 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).
• Core Exclusion Criteria:
• - Any significant laboratory finding or any severe and uncontrolled medical condition.
• - Participants with any known predisposition to bleeding.
• - Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.
• - Allogenic organ transplantation.
• - Known to have active infection, including hepatitis B virus (HBV) or hepatitis C virus (HCV).
• - Known history of infection with human immunodeficiency virus (HIV).
• - Active gastrointestinal disease or other condition that will interfere significantly with the swallowing, absorption, distribution, metabolism or excretion of oral therapy.
• - Participants with history of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
• - Participants with a known hypersensitivity to the investigational product(s) or any of the excipients of the product(s).
• - Previous dosing with AZD4956.