In short
AZD4956 is an investigational oral substance being studied for advanced or metastatic solid tumours with defects in homologous recombination repair. One authorised Phase 1/2 trial (NCT07446855) is currently assessing its safety, tolerability, and preliminary efficacy, both alone and in combination with other anti-cancer agents, in up to 180 participants.
Key points
- AZD4956 is an investigational oral therapy for advanced solid tumours with homologous recombination repair defects.
- The single authorised trial is Phase 1/2 and plans to enrol up to 180 participants.
- The study tests AZD4956 as monotherapy and in combination with anti-cancer agents such as saruparib.
- Part A focuses on dose escalation and Part B on dose expansion to assess preliminary anti-tumour activity.
- Key endpoints include safety, tolerability, pharmacokinetics, and radiological response by RECIST v1.1.
- The trial is currently authorised, meaning it is approved to begin or is ongoing.
What is AZD4956?
AZD4956 is an investigational oral substance under evaluation for the treatment of advanced or metastatic solid tumours with defects in homologous recombination repair (HRR). Homologous recombination repair is a cellular mechanism that fixes damaged DNA; when it is defective, cancer cells may be more vulnerable to certain treatments. The substance is not yet authorised as a medicine and is currently being studied in a modular, open-label Phase 1/2 trial known as PARTHENON.
In the trial, AZD4956 is given orally and is being investigated both as a single agent (monotherapy) and in combination with other anti-cancer agents, including saruparib, another oral drug.
How does AZD4956 work?
The precise mechanism of action of AZD4956 is not described in the available trial record. The study focuses on participants whose tumours have homologous recombination repair defects, suggesting that AZD4956 may interfere with DNA repair pathways in cancer cells, but the registry does not state the molecular target.
Which conditions is AZD4956 studied for?
- Advanced or metastatic solid tumours with homologous recombination repair defects — the trial enrols participants with solid tumours that have spread and carry defects in a specific DNA repair pathway.
How is AZD4956 given?
AZD4956 is administered orally, according to the trial record. The study evaluates ascending doses, meaning the amount given is gradually increased to find a safe and tolerable dose.
What do the clinical trials show?
One authorised Phase 1/2 trial (NCT07446855) is registered for AZD4956. The trial is modular and open-label, meaning both participants and researchers know which treatment is being given. It is divided into two parts: Part A involves dose escalation to assess safety and tolerability of AZD4956 alone and in combination with other anti-cancer agents, while Part B involves dose expansion to assess preliminary anti-tumour activity of the combination.
What are the trials measuring?
For Part A, the trial measures the incidence of dose-limiting toxicities (DLTs), adverse events, serious adverse events, and changes from baseline in physical examination, vital signs, electrocardiograms (ECGs), and laboratory findings. For Part B, it additionally measures radiological response according to RECIST v1.1, a standard way to assess tumour shrinkage, and progression-free survival (PFS), the time without disease worsening.
Who can take part in these trials?
The trial enrols participants with advanced or metastatic solid tumours that have homologous recombination repair defects. The planned enrolment is 180 participants.
What is the status of the trial?
The trial is currently authorised, meaning it has received regulatory approval to proceed.