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

NCT05514132 | Active Not Recruiting Phase 1

• 1 other identifier: D5330C00017
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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

Conditions

Advanced Solid Tumours

Keywords

Phase 1; Safety; Tolerability; Pharmacokinetics; Advanced solid tumours

Outcome Measures

Primary Outcomes (2)

• The number of subjects with dose-limiting toxicity, as defined in the protocol.

  Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optional therapeutic intervention, meets protocol-defined criteria.

  From the first dose of study treatment Up to and including the end of cycle 1(each cycle is 28 days) .

• Safety and tolerability in terms of adverse events

  Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

  From the first dose of study treatment until 28 days after the last dose.

Secondary Outcomes (6)

• Plasma ceralasertib concentration(Cmax)

  Cycle 0 Day1 to Day7, Cycle1 Day1 and Cycle 1 Day 7 or Day 8. At the end of Cycle1(each cycle is 28 days)

• Area under the plasma concentration versus time curve(AUC)

  Cycle 0 Day1 to Day7, Cycle1 Day1 and Cycle1 Day7 or Day8. At the end of Cycle1(each cycle is 28 days)

• Overall response rate

  At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28days) until objective disease progression as defined by RECIST version 1.1

• Duration of Response

  At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28 days) until objective disease progression as defined by RECIST version 1.1

• Percentage Change in Tumour Size

  At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28 days) until objective disease progression as defined by RECIST version 1.1

Study Arms (1)

Ceralasertib in Combination with Durvalumab

EXPERIMENTAL

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

Drug: Ceralasertib; Drug: Durvalumab

Interventions

Ceralasertib 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.

Also known as: Ceralasertib taken orally

Ceralasertib in Combination with Durvalumab

Durvalumab 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.

Also known as: Durvalumab Infusion

Ceralasertib in Combination with Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent.
• At least 18 years of age at the time of signing the ICF.
• 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.
• Ability to swallow oral medication intact and retain it.
• ECOG/WHO performance status of 0 to 1.
• Must have a life expectancy of at least 12 weeks.
• Participant must have had a treatment-free interval of ≥ 3 weeks from any prior therapy before the first dose of study treatment.
• 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).
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• Inadequate bone marrow reserve or organ function
• 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.
• Spinal cord compression, leptomeningeal disease, or brain metastases, unless asymptomatic, treated, stable, and not requiring continuous corticosteroids
• As judged by the investigator, any active disease or condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy
• History of another primary malignancy.
• 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.
• Known history of HIV infection.
• Active cardiacvascular disease be consider as clinical significant.
• Active or prior documented autoimmune or inflammatory disorders
• Prior exposure to a CHK1 or ATR inhibitor.
• As judged by the investigator, any unresolved treatment-related toxicities from previous anti-cancer therapy of CTCAE v5.0 Grade ≥ 2
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
• Participants must not have experienced a toxicity that led to permanent discontinuation of prior anti-PD-1 or anti-PD-L1 immunotherapy.
• 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
• Participants with a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Beijing, 100021, China

Location

Research Site

Shandong, China

Location

MeSH Terms

Interventions

ceralasertib; durvalumab

Study Officials

• Jie Wang, PHD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: August 24, 2022
• Study Start: September 23, 2022
• Primary Completion: October 20, 2023
• Study Completion: March 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma 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 de-identified individual patient-level datain an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (2)