A Study to Evaluate the Safety and Pharmacokinetics of Ceralasertib in Combination With Durvalumab in Chinese Patients With Advanced Solid Tumours

NCT ID: NCT05514132

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-23
• Study Completion Date: 2026-03-31

Brief Summary

This is a Phase 1, open-label study of ceralasertib given in combination with durvalumab in Chinese participants with advanced solid tumours. In each cohort, a monotherapy lead-in period (Cycle 0, duration of 7 or 14 days), prior to dosing with durvalumab, is added to investigate the PK profile and safety/tolerability of ceralasertib in Chinese participants.

This study is designed to investigate and characterise preliminary safety, tolerability, and PK of ceralasertib in DLT-evaluable Chinese participants

Detailed Description

<Objectives>

Primary Objective:

To assess the safety and tolerability of ceralasertib in combination with durvalumab in Chinese patients with advanced solid tumours refractory/resistant to prior SoC therapy or for which no appropriate SoC therapy exists.

Secondary Objective:

To characterise the PK profile of ceralasertib after single- and multiple-doses administration. To characterise the anti-tumour activity and efficacy of ceralasertib in combination with durvalumab in Chinese patients .

<Overall design> This is a Phase 1, open-label study of ceralasertib given in combination with durvalumab in Chinese patients with advanced solid tumours.Results from this study will provide dose rationale for future investigations.

Conditions

Advanced Solid Tumours

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ceralasertib in Combination with Durvalumab

This is a sequential group treatment/dose-escalation study with 2 cohorts with no masking.

Group Type: EXPERIMENTAL

Ceralasertib

Intervention Type: DRUG

Ceralasertib (AZD6738) is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ATR, with good selectivity against other phosphatidylinositol 3-kinase-related kinase family members.

Durvalumab

Intervention Type: DRUG

Durvalumab is a human mAb of the immunoglobulin G 1 kappa subclass that blocks the interaction of PD-L1 (but not PD-L2) with PD-1 on T cells and CD80 (B7.1) on immune cells.

Interventions

Ceralasertib

Ceralasertib (AZD6738) is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ATR, with good selectivity against other phosphatidylinositol 3-kinase-related kinase family members.

Intervention Type: DRUG

Durvalumab

Durvalumab is a human mAb of the immunoglobulin G 1 kappa subclass that blocks the interaction of PD-L1 (but not PD-L2) with PD-1 on T cells and CD80 (B7.1) on immune cells.

Intervention Type: DRUG

Other Intervention Names

Ceralasertib taken orally; Durvalumab Infusion

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent.

2. At least 18 years of age at the time of signing the ICF.

3. Histological or cytological confirmation advanced solid tumour with refractory/resistance to a prior line of anti-PD-1/PD-L1-containing therapy (received as monotherapy or in combination) or for which no SoC exists.

4. Ability to swallow oral medication intact and retain it.

5. ECOG/WHO performance status of 0 to 1.

6. Must have a life expectancy of at least 12 weeks.

7. Participant must have had a treatment-free interval of ≥ 3 weeks from any prior therapy before the first dose of study treatment.

8. Body weight > 35 kg and no cancer-associated cachexia (eg, CTCAE Grade 2 or worse weight loss over the 3 months prior to the Screening Visit).

9. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria

1. Inadequate bone marrow reserve or organ function

2. As judged by the investigator, any evidence of uncontrolled intercurrent illness, that in the investigator's opinion makes it undesirable for the participant to participate in the study.

3. Spinal cord compression, leptomeningeal disease, or brain metastases, unless asymptomatic, treated, stable, and not requiring continuous corticosteroids

4. As judged by the investigator, any active disease or condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy

5. History of another primary malignancy.

6. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection including any patient known to have hepatitis B, hepatitis C, and HIV.

7. Known history of HIV infection.

8. Active cardiacvascular disease be consider as clinical significant.

9. Active or prior documented autoimmune or inflammatory disorders

10. Prior exposure to a CHK1 or ATR inhibitor.

11. As judged by the investigator, any unresolved treatment-related toxicities from previous anti-cancer therapy of CTCAE v5.0 Grade ≥ 2

12. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.

13. Participants must not have experienced a toxicity that led to permanent discontinuation of prior anti-PD-1 or anti-PD-L1 immunotherapy.

14. Participants must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged

15. Participants with a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

17. 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.

18. Previous enrolment in the present study.

19. For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jie Wang, PHD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

Research Site

Beijing, , China

Research Site

Shandong, , China

Countries

China

Other Identifiers

D5330C00017

Identifier Type: -

Identifier Source: org_study_id