NCT07446855

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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
180

participants targeted

Target at P75+ for phase_1

Timeline
47mo left

Started Mar 2026

Longer than P75 for phase_1

Geographic Reach
6 countries

18 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress4%
Mar 2026Mar 2030

First Submitted

Initial submission to the registry

February 26, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 3, 2026

Completed
14 days until next milestone

Study Start

First participant enrolled

March 17, 2026

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 29, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 29, 2030

Last Updated

April 20, 2026

Status Verified

April 1, 2026

Enrollment Period

4 years

First QC Date

February 26, 2026

Last Update Submit

April 17, 2026

Conditions

Solid Tumours

Keywords

Advanced/metastatic homologous recombination repair defective solid tumoursPoly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)PharmacokineticsPharmacodynamics

Outcome Measures

Primary Outcomes (3)

  • 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).

    From Screening (Day -28) to follow-up (up to 3.5 years)

  • 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.

    Up to 3.5 years

  • 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).

    Up to 28 days

Secondary Outcomes (23)

  • Objective response (OR)

    Up to 3.5 years

  • Duration of response (DoR)

    Up to 3.5 years

  • Best Overall Response (BOR)

    Up to 3.5 years

  • Time to response (TTR)

    Up to 3.5 years

  • Disease control (DC)

    Up to 3.5 years

  • +18 more secondary outcomes

Study Arms (6)

Module 1 Part A: AZD4956 monotherapy (Dose escalation)

EXPERIMENTAL

Participants will receive AZD4956 as monotherapy at ascending dose levels.

Drug: AZD4956

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

EXPERIMENTAL

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

Drug: AZD4956Drug: Saruparib

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

EXPERIMENTAL

Participants will receive AZD4956 in combination with saruparib.

Drug: AZD4956Drug: Saruparib

Module 2 Part A Optional PD backfill cohort: Saruparib monotherapy

EXPERIMENTAL

Participants will receive saruparib monotherapy.

Drug: Saruparib

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

EXPERIMENTAL

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

Drug: AZD4956Drug: Saruparib

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

EXPERIMENTAL

Participants will receive AZD4956 in combination with saruparib.

Drug: AZD4956Drug: Saruparib

Interventions

AZD4956DRUG

AZD4956 will be administered orally.

Module 1 Part A: AZD4956 monotherapy (Dose escalation)Module 2 Part A Optional PD backfill cohort: AZD4956 + saruparibModule 2 Part A Optional non-PD backfill cohort: AZD4956 + saruparibModule 2 Part A: AZD4956 + saruparib (Dose escalation)Module 2 Part B: AZD4956 + saruparib (Dose expansion)
SaruparibDRUG

Saruparib will be administered orally.

Module 2 Part A Optional PD backfill cohort: AZD4956 + saruparibModule 2 Part A Optional PD backfill cohort: Saruparib monotherapyModule 2 Part A Optional non-PD backfill cohort: AZD4956 + saruparibModule 2 Part A: AZD4956 + saruparib (Dose escalation)Module 2 Part B: AZD4956 + saruparib (Dose expansion)

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • +8 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Research Site

New York, New York, 10065, United States

NOT YET RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

NOT YET RECRUITING

Research Site

Houston, Texas, 77030, United States

NOT YET RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

RECRUITING

Research Site

Melbourne, 3000, Australia

NOT YET RECRUITING

Research Site

Westmead, 2145, Australia

NOT YET RECRUITING

Research Site

Chūōku, 104-0045, Japan

NOT YET RECRUITING

Research Site

Kashiwa, 277-8577, Japan

NOT YET RECRUITING

Research Site

Seoul, 03080, South Korea

NOT YET RECRUITING

Research Site

Seoul, 120-752, South Korea

NOT YET RECRUITING

Research Site

Barcelona, 08023, Spain

NOT YET RECRUITING

Research Site

Barcelona, 08036, Spain

NOT YET RECRUITING

Research Site

Barcelona, 8035, Spain

NOT YET RECRUITING

Research Site

Logroño, 26006, Spain

NOT YET RECRUITING

Research Site

Pozuelo de Alarcón, 28223, Spain

NOT YET RECRUITING

Research Site

Seville, 41013, Spain

NOT YET RECRUITING

Research Site

London, SE1 9RT, United Kingdom

NOT YET RECRUITING

Research Site

Sutton, SM25PT, United Kingdom

NOT YET RECRUITING

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 26, 2026

First Posted

March 3, 2026

Study Start

March 17, 2026

Primary Completion (Estimated)

March 29, 2030

Study Completion (Estimated)

March 29, 2030

Last Updated

April 20, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

Locations

KR(2)JP(2)US(4)AU(2)ES(6)GB(2)