Evaluating the absorption and metabolism of Saruparib in patients with advanced solid tumors

A Phase I, Open-label Study to Assess the Absolute Bioavailability of Saruparib (AZD5305) and Absorption, Distribution, Metabolism, and Excretion (ADME) of [14C]-Saruparib ([14C]-AZD5305) in Patients With Advanced Solid Malignancies

This study is testing how well a new cancer drug called Saruparib is absorbed and processed in the body of patients with advanced solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Liverpool and 1 other locations)
• Trial ID: NCT06713369 on ClinicalTrials.gov

What this trial studies

This Phase I, open-label study investigates the bioavailability and pharmacokinetics of Saruparib (AZD5305) in patients with advanced solid malignancies. The study consists of two parts: Part A involves a single-dose oral administration of Saruparib along with a radiolabeled microtracer, while Part B assesses the absorption, distribution, metabolism, and excretion (ADME) of the drug. Participants will be monitored in a hospital setting for safety and to collect various biological samples. The study aims to provide insights into how the drug behaves in the body, which is crucial for its future development.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with locally advanced or metastatic solid tumors for which standard therapies are ineffective or intolerable.

Not a fit: Patients with lymphoma or those who do not meet the eligibility criteria, such as those with a poor ECOG performance status, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of Saruparib's pharmacokinetics, potentially leading to improved treatment options for patients with advanced solid tumors.

How similar studies have performed: While this study explores the pharmacokinetics of Saruparib, similar studies have shown promise in understanding drug behavior in patients with advanced malignancies.

Eligibility criteria

Inclusion Criteria:

1. Male or female ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the ICF.
2. Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
3. ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to dosing.
4. Predicted life expectancy ≥ 12 weeks.
5. Adequate organ and marrow function as defined in the protocol
6. Willingness and ability to comply with study and follow-up procedures.
7. Able and willing to stay in hospital for specified residential periods following administration of Saruparib/\[14C\]-Saruparib
8. Regular bowel movements
9. Body weight within normal range specified in protocol
10. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Reproduction
11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol

Exclusion Criteria:

1. Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML is not required.
2. Participants with any known predisposition to bleeding
3. Any history of persisting severe cytopenia due to any cause
4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of Saruparib.
5. History of another primary malignancy, with some exceptions
6. Persistent toxicities (CTCAE Grade ≥ 2), excluding alopecia, caused by previous anticancer therapy.
7. Spinal cord compression or brain metastases for at least 4 weeks prior to start of study intervention unless asymptomatic and stable
8. Abnormal cardiac function exclusions or cardiovascular disease
9. History of arrhythmia
10. Active HBV (positive HBsAg result) or HCV.
11. Evidence of active and uncontrolled HIV infection.
12. Active tuberculosis infection
13. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
14. As judged by the investigator, any other evidence of diseases (such as severe or uncontrolled systemic diseases or active uncontrolled infections which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol.
15. Any prior treatment with a PARP inhibitor or platinum chemotherapy.
16. Other anticancer therapy (chemotherapy, immunotherapy, hormonal anticancer therapy, radiotherapy \[except for palliative local radiotherapy\]), biological therapy or other novel agent is not permitted until the last PK sampling is completed.
17. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
18. Concomitant use of medications or herbal supplements known to be CYP3A4 strong and moderate inhibitors or inducers
19. Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes
20. Participants who have participated in another absorption, distribution, metabolism, and excretion study within 1 year prior to screening.
21. Participation in another clinical study with a study intervention administered in the last 3 months or 5 half-lives prior to dosing, whichever is longer.
22. Participants with a known hypersensitivity to Saruparib or any of the excipients of the product.
23. Participants who have been administered any amount of a \[14C\]-labelled compound within the last 12 months.
24. Use of tobacco- or nicotine-containing products or alcohol may be exclusionary
25. Poor peripheral venous access (venous access via a port will be permitted).
26. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
27. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
28. Previous enrolment in the present study.
29. For female participants only: currently pregnant (confirmed with positive pregnancy test) or planning to become pregnant, breast-feeding, or intending to donate/retrieve ova before 6 months after the last dose of Saruparib.

Where this trial is running

Liverpool and 1 other locations

• Research Site — Liverpool, United Kingdom (Recruiting)
• Research Site — Manchester, United Kingdom (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Locally Advanced or Metastatic Solid Tumor; hADME; saruparib; AZD5305; advanced solid tumour / tumor; neoplasm