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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Research Site
  New York, New York, United States Recruiting
• Research Site
  Providence, Rhode Island, United States Recruiting
• Research Site
  Houston, Texas, United States Recruiting
• Research Site
  Fairfax, Virginia, United States Recruiting
• Research Site
  Melbourne, Australia Recruiting
• Research Site
  Westmead, Australia Recruiting

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.