Recruiting
Phase 1
Phase 2

AZD4956

Sponsor:

AstraZeneca

Code:

NCT07446855

Conditions

Solid Tumours

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

AZD4956

Saruparib

Study Details

Brief summary:

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.

Conditions

Solid Tumours

Study ID

NCT07446855

Start date

Mar 17, 2026

Status verified date

Sep, 2026

Completion date

Mar 29, 2030

Anticipated

Primary completion date

Mar 29, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

180 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Module 1 Part A: AZD4956 monotherapy (Dose escalation)

Participants will receive AZD4956 as monotherapy at ascending dose levels.

experimental: Module 2 Part A: AZD4956 + saruparib (Dose escalation)

Participants will receive AZD4956 at ascending dose levels in combination with saruparib.

experimental: Module 2 Part A Optional PD backfill cohort: AZD4956 + saruparib

Participants will receive AZD4956 in combination with saruparib.

experimental: Module 2 Part A Optional PD backfill cohort: Saruparib monotherapy

Participants will receive saruparib monotherapy.

experimental: Module 2 Part A Optional non-PD backfill cohort: AZD4956 + saruparib

Participants with metastatic castrate resistant prostate cancer (mCRPC) will receive AZD4956 in combination with saruparib.

experimental: Module 2 Part B: AZD4956 + saruparib (Dose expansion)

Participants will receive AZD4956 in combination with saruparib.

Interventions

AZD4956

AZD4956 will be administered orally.

Saruparib

Saruparib will be administered orally.

Primary outcome measure

  • Parts A and B: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From Screening (Day -28) to follow-up (up to 3.5 years) ]
  • Part B: Progression free survival (PFS) [ Time Frame: Up to 3.5 years ]
  • Part A - Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

New York, New York, United States, 10065

Research Site

Recruiting

Houston, Texas, United States, 77030

Research Site

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

AstraZeneca

Last update posted

Sep 8, 2026

Last verified

Sep, 2026

Keywords

  • Advanced/metastatic homologous recombination repair defective solid tumours
  • Poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)
  • Pharmacokinetics
  • Pharmacodynamics

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-09-08.