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AZD4956 alone or with saruparib for advanced HRR-deficient solid tumors

A 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

PHASE1; PHASE2 · AstraZeneca · NCT07446855

This will test AZD4956 by itself and together with saruparib in people who have advanced or metastatic solid tumors with homologous recombination repair defects.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment180 (estimated)
Ages18 Years to 130 Years
SexAll
SponsorAstraZeneca (industry)
Locations18 sites (New York, New York and 17 other locations)
Trial IDNCT07446855 on ClinicalTrials.gov

What this trial studies

This is a modular, first-in-human program that explores escalating doses of AZD4956 as monotherapy and in combination with saruparib in participants with advanced or metastatic solid tumors harboring homologous recombination repair (HRR) deficiencies. Each module has a dose‑escalation Part A to determine safety, tolerability, pharmacokinetics, and pharmacodynamics, and a Part B dose‑expansion to further characterize safety and preliminary anti‑tumor activity. Key outcomes include dose‑limiting toxicities, adverse events, drug exposure measures, biomarker changes, and early signals of tumor response. The trial enrolls participants with ECOG 0–1 and adequate organ and marrow function at several US research sites.

Who should consider this trial

Good fit: Ideal participants are adults with documented advanced or metastatic solid tumors with HRR defects, ECOG performance status 0–1, adequate organ function, and an expected life expectancy of at least 12 weeks.

Not a fit: Patients without HRR deficiencies, those with ECOG >1 or significant organ dysfunction, and pregnant or breastfeeding individuals are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, AZD4956 alone or with saruparib could shrink tumors or slow disease progression in patients with HRR-deficient cancers and provide a new treatment option.

How similar studies have performed: PARP inhibitors have demonstrated benefit in HRR‑deficient cancers and combinations with targeted agents have shown promise, but AZD4956 is first‑in‑human and its clinical activity is unproven.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

New York, New York and 17 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Solid Tumours, Advanced/metastatic homologous recombination repair defective solid tumours, Poly polymerase inhibitor, Pharmacokinetics, Pharmacodynamics

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.