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Safety and Tolerability of AZD4956 Alone or with Saruparib in Adults with Advanced Metastatic Solid Tumors (Phase I/IIa)

Verified siteInvestigationalNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on people with advanced or metastatic solid tumors that have a problem with a DNA‑repair system called homologous recombination repair defective. The investigational medicine being tested is an oral tablet named AZD4956. In some parts of the study the drug is given alone, and in other parts it is taken together with another oral cancer medicine called saruparib. Both medicines are taken by mouth in tablet form.

The purpose of the study is to evaluate the safety of the medicines and to see how they affect the cancer. Participants will start with a low dose that is gradually increased, and they will have regular clinic visits for physical checks, blood tests, heart monitoring, and imaging scans to look at the tumors. The scans are read using a standard system known as RECIST to see if the tumors shrink or grow. Throughout the trial, researchers will also measure how the drug moves through the body (pharmacokinetics) and how it influences cancer cells (pharmacodynamics). The study lasts for several months, with follow‑up visits after treatment ends to monitor any lasting effects.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Baseline assessments
After joining the study, you will undergo a series of baseline checks that include a physical examination, measurement of vital signs, an electrocardiogram (ecg), and laboratory tests. a tumor scan will be performed to document the size and location of the cancer, and a small tissue sample may be taken to study biomarkers. these assessments create a reference point for evaluating safety and treatment effects.
Step 2
Start of azd4956 monotherapy (dose escalation)
You will begin taking azd4956, an oral film‑coated tablet, exactly as instructed by the study team, usually once daily. the dose may be increased in later groups of patients to find the highest amount that can be tolerated safely. blood samples will be collected at scheduled times to measure how the drug moves through your body (pharmacokinetics, pk) and to assess its biological effects (pharmacodynamics, pd).
Step 3
Addition of saruparib (combination therapy)
If you are assigned to the combination part of the trial, an oral tablet of saruparib will be added to your regimen. you will take this medication as directed, typically once daily, together with azd4956. the same safety monitoring and blood sampling will continue.
Step 4
Regular safety monitoring visits
Throughout the treatment period you will attend scheduled clinic visits. during each visit, vital signs, lab tests, and any symptoms will be recorded. any side effects will be classified as adverse events (ae) or serious adverse events (sae). the study will also track dose‑limiting toxicities (dlt), which are side effects that prevent further dose increases.
Step 5
Radiological response assessments
Tumor imaging scans will be repeated at defined intervals to evaluate changes in tumor size. the response will be measured using the standardized criteria known as recist version 1.1. these results help determine whether the treatment is having an anti‑tumor effect.
Step 6
Continuation of treatment
You will continue taking the study medication(s) until one of the following occurs: disease progression (tumor growth), unacceptable side effects, or completion of the planned treatment period as defined by the protocol.
Step 7
End‑of‑treatment visit
When treatment stops, a final assessment will be performed. this includes a physical exam, lab tests, an ecg, and a tumor scan to document the status at the end of therapy.
Step 8
Post‑treatment follow‑up
After the end‑of‑treatment visit, you will be followed for a period of time to monitor long‑term safety and to collect information on progression‑free survival (pfs), which measures the time until the cancer grows or new symptoms appear.

Who can join the trial?

24 criteria

Be able to sign a written informed consent form agreeing to follow the study rules.
If you are a woman, you must not be breastfeeding and must not donate or retrieve eggs from the start of the study until about 6 months after the last dose.
If you are a man, you must use a condom plus another birth‑control method during the study and for about 6 months after the last dose, and you must not father a child or donate sperm during that time.
You must be willing and able to follow the study schedule, including taking the medication and attending all required visits.
You must be able to swallow the oral medication whole and keep it in your mouth without spitting it out.
For the first part of the study (Part A), you need proof that your disease is getting worse on scans after standard treatment that normally helps.
You must have advanced or metastatic solid tumors and have a local genetic test result as required by the study. (Tumors that are stromal, sex‑cord, or germ‑cell are not allowed, but carcinosarcoma is allowed.)
You may have had up to one previous treatment that included a PARP inhibitor (PARPi)‑based regimen, either as therapy or maintenance.
You must have disease that can be measured or evaluated according to the study’s definitions.
If you are in a “PD backfill” group, you must not have had any prior PARPi‑based treatment. In dose‑escalation groups, one prior PARPi treatment is allowed but not required.
The doctor must feel that you are a suitable candidate for treatment with a PARP inhibitor.
You must agree to give a baseline tumor sample before starting treatment, if required for your study module.
You must have documented metastatic disease showing at least one bone lesion (a spot that lights up on a bone scan) and/or at least one soft‑tissue lesion (a tumor in muscle, fat, or other tissue).
If you have metastatic prostate cancer, you must have received at least one but no more than two prior androgen‑receptor‑targeted therapies (ARPI) and, if needed, one or two prior taxane‑based chemotherapies.
If you cannot receive chemotherapy or other standard treatments, you may still be considered if all options have been discussed and the doctor believes the trial is the best next step.
You must not have had any prior PARPi‑based therapy if you are in the non‑PD or Part B groups.
You must be 18 years old or older (or the legal age of consent in your country) at the time you sign the consent form.
You must have a confirmed locally advanced or metastatic solid‑tumor cancer, as specified for each study module.
Your overall health must be good enough to have an ECOG performance status of 0 or 1, with no worsening in the two weeks before screening.
The doctor must estimate that you have at least 12 weeks of life expectancy.
Your blood, liver, kidney, and bone‑marrow function must be adequate for the study.
Both men and women of any gender identity can enroll.
If you are a woman who could become pregnant, you must have a negative pregnancy test at screening and before each treatment cycle.
A woman who could become pregnant and is sexually active with a male partner must use a highly effective birth‑control method plus a barrier method (like a condom with spermicide) from screening until about 6 months after the last dose. Hormonal birth‑control methods are not allowed.

Who cannot join the trial?

17 criteria

If you have any serious laboratory abnormality or an uncontrolled medical problem—such as uncontrolled hypertension (high blood pressure that is not under control), bleeding diathesis (a tendency to bleed easily), hepatic failure (severe liver failure), unstable breathing or heart conditions, active interstitial lung disease (a scarring lung condition), or an infection that needs treatment—you cannot join the study.
If you have an active stomach or intestinal disease, or any condition that makes it hard to swallow, absorb, distribute, metabolize, or eliminate an oral medication, you cannot join.
If you have a history of another primary cancer, you are excluded unless that cancer was treated with the goal of cure, you have been disease‑free for at least two years, or it was a non‑melanoma skin cancer, a carcinoma in situ (early‑stage cancer that has not spread), or a non‑invasive skin cancer being monitored.
If you have a past diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) (blood cancers), or any signs that suggest these conditions, you cannot join.
If you still have moderate or severe side effects (CTCAE Grade 2 or higher) from previous cancer treatment—except hair loss—you are not eligible, unless the side effect is permanent and not expected to get worse.
If you are taking any medication that the study lists as prohibited and you cannot stop it for at least 21 days (or five half‑lives, whichever is longer) before the first dose and until 30 days after the last dose, you cannot join.
If you are using medicines that are known to lengthen the QTc interval (a measurement of the heart’s electrical activity), you cannot take them from the first dose through the safety review period or during scheduled heart tests.
If you are receiving any other cancer treatment at the same time, you cannot participate (hormone therapy for non‑cancer reasons is allowed).
If your scans do not show measurable disease in both bone and soft tissue—as defined by a “superscan” bone scan and no assessable soft‑tissue lesion by RECIST v1.1 criteria—you are not eligible.
If you have any condition that makes you prone to bleeding, such as an active stomach ulcer or proliferative diabetic retinopathy (advanced eye disease from diabetes), you cannot join.
If you have spinal cord compression, active and unstable brain metastases (cancer spread to the brain), or leptomeningeal disease (cancer spread to the membranes covering the brain), you are excluded.
If you have received an organ transplant from another person (allogenic transplantation), you cannot participate.
If you have any heart condition that meets the cardiac criteria listed in the study protocol, you are not eligible.
If you have other cardiovascular (heart or blood‑vessel) diseases as defined by the study, you cannot join.
If you have a current infection, including hepatitis B or hepatitis C (viruses that affect the liver), you are excluded.
If you have a known infection with HIV (human immunodeficiency virus), you cannot participate.
If you have had a severe drop in all blood cell types for more than two weeks—such as very low white blood cells (ANC < 0.5 × 10⁹/L) or low platelets (platelets < 50 × 10⁹/L)—you are not eligible.

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Verified sites

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Hospital Clinic De Barcelona
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Barcelona, Spain
Hospital Vall d’Hebron
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Barcelona, Spain

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Investigated drugs

AZD4956
is an experimental oral tablet that is being studied to see if it is safe and well‑tolerated when given alone or together with other cancer medicines. In this trial, participants with advanced solid tumors that have a specific DNA repair problem will take AZD4956 so researchers can learn how the drug is absorbed and processed in the body, how it affects the tumor, and whether it shows any early signs of helping to shrink or control the cancer.
Saruparib
is another experimental oral tablet that is being tested as a cancer treatment. In the study, it is given in combination with AZD4956 to explore whether the two drugs together are safe and can work against tumors. Researchers will watch for side effects, how the body handles the medication, and any early evidence that the combination may help slow tumor growth in patients with advanced solid tumors.

Saruparib

What is already known about the treatment

AZD4956
This experimental drug is taken by mouth as a film‑coated tablet. It is currently in early clinical trials and not yet approved for general medical use. AZD4956 is being studied for solid tumors that have problems repairing DNA, especially those with homologous recombination repair defects. It works by blocking a protein called PARP that cancer cells use to fix DNA damage, classifying it as a PARP inhibitor and an anti‑cancer agent.
Saruparib
This investigational medication is also taken orally in tablet form. It remains in the research stage and has not received regulatory approval. Saruparib is being evaluated for use in solid tumors, particularly those with defective DNA repair mechanisms. It inhibits the same PARP protein that helps cancer cells survive DNA damage, placing it in the PARP inhibitor class of anti‑cancer drugs.

Investigated diseases

Solid Tumors - Solid tumors are abnormal clumps of cells that form a mass in organs or tissues. They usually begin as a small lump and gradually increase in size. As they grow, they can invade nearby structures and may enter the bloodstream or lymphatic system, leading to new growths in distant sites. This spread is called metastasis and represents a later stage of tumor development.