The purpose of this modular, first trial in human study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of ascending dose levels (DLs) of AZD4956 monotherapy and in combination with other anti-cancer agents in participants with advanced/metastatic solid tumours with homologous recombination repair (HRR) deficiencies.
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.
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.
Sequential
AZD4956
DrugAZD4956 will be administered orally.
Saruparib
DrugSaruparib will be administered orally.
6
Treatment groupsSee each treatment group below.
Parts A and B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s).
Part B: Progression free survival (PFS)
PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression.
Part A - Number of participants with dose-limiting toxicities (DLTs)
To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s).
Objective response (OR)
OR is defined as if a participant achieves a best overall response (BOR) of confirmed complete response (CR) or partial response (PR), as assessed by the investigator, according to response evaluation criteria in solid tumours (RECIST) v1.1 criterion.
Duration of response (DoR)
DoR is defined as the time from the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by prostate cancer working group 3 (PCWG3), until the date of documented disease progression or death in the absence of disease progression.
Best Overall Response (BOR)
To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer agent(s).
Time to response (TTR)
TTR is defined as the time from the date of first dose of study intervention until the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, which is subsequently confirmed.
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