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

Inclusion Criteria23

• 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.
• 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).
• Part A (AZD4956 in Combination with Saruparib Dose Escalation) and Part A-PD (PD Backfill Cohorts):
• Participants must have one of the following conditions-
• 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.
• Histologically or cytologically confirmed advanced ovarian, fallopian tube, or primary peritoneal cancer.
• Histologically or cytologically confirmed adenocarcinoma of the prostate and advanced/metastatic castrate resistant prostate cancer (CRPC).
• 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).