Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Solid Tumors
Phase II Trial of Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Selected Solid Tumor Malignancies
2 other identifiers
interventional
83
1 country
3
Brief Summary
This phase II trial studies how well ceralasertib, am Ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor, works alone or in combination with olaparib or durvalumab in treating participants with renal cell carcinoma (RCC), urothelial carcinoma, all pancreatic cancers, endometrial cancer, and other solid tumors excluding clear cell ovarian cancer that have spread to nearby tissue or lymph nodes or other parts of the body. ATR kinase inhibitor AZD6738 and olaparib or durvalumab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not known if giving ATR kinase inhibitor AZD6738 with or without olaparib or durvalumab may work better in treating participants with solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2019
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 21, 2018
CompletedFirst Posted
Study publicly available on registry
September 24, 2018
CompletedStudy Start
First participant enrolled
January 17, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2028
April 23, 2026
April 1, 2026
9.2 years
September 21, 2018
April 20, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Objective response rate (ORR) (ARID1A cohort)
On overall response will be reported as a percentage of participants with a complete response (CR) or partial response (PR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Up to 3 years
Composite Prostate Cancer Patient Response Rate (prostate cancer only)
In prostate cancer patients only: To determine the 50% decline in prostate-specific antigen (PSA50) response rate Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or objective response by RECIST 1.1
Up to 3 years
Objective response rate (ORR) for other solid tumors
ORR for participants with other solid tumors will be measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Will be based on one-sided exact binomial test comparison of the observed ORR in evaluable patients to the null-hypothesized value of 5%, using the 5% significance level.
Up to 3 years
Objective response rate (ORR) for endometrial cohort
ORR for participants with endometrial cancers will be measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Will be based on one-sided exact binomial test comparison of the observed ORR in evaluable patients to the null-hypothesized value of 5%, using the 5% significance level.
Up to 3 years
Secondary Outcomes (12)
Median duration of response (DOR) by treatment regimen
Up to 3 years
Median duration of response (DOR) by disease group
Up to 3 years
Median progression-free survival (PFS) at 6 months by treatment regimen
6 months
Median progression-free survival (PFS) at 12 months by treatment regimen
12 months
Median progression-free survival (PFS) at 6 months by disease group
6 months
- +7 more secondary outcomes
Study Arms (3)
Arm I (Ceralasertib Monotherapy)
EXPERIMENTALAs monotherapy ceralasertib will be given at a starting dose of 160 mg two times per day (BID), on days 1-14 of a 28-day cycle for participants who are BAF250a negative or show an ATM-Mutation by CLIA assay. Treatment will continue until disease progression, unacceptable toxicity, or participant withdrawal from study, whichever occurs first.
Arm II (Ceralasertib, Olaparib)
EXPERIMENTALIn combination with olaparib, ceralasertib will be given at a continuous daily dose of 160 mg daily days 1-7 in each 28-day cycle. Olaparib will be given at a starting dose of 300 mg twice daily days 1-28 of a 28-day cycle for participants who are BAF250a positive. Treatment will continue until disease progression, unacceptable toxicity, or participant withdrawal from study, whichever occurs first.
Arm III (Ceralasertib, Durvalumab)
EXPERIMENTALIn combination with durvalumab, ceralasertib will be given at a continuous daily dose of 240 mg BID days 1-7 of a 28-day dosing schedule. Durvalumab will be given at a flat dose of 1500 mg IV on day 8 of a 28-day cycle for participants with histologically confirmed endometrial cancers. Participants treated with the combination of ceralasertib plus durvalumab may continue treatment beyond first radiographic progression until the occurrence of either confirmed radiographic progression or clinical progression, whichever occurs first.
Interventions
Given orally
Given orally
Given intravenously (IV)
Eligibility Criteria
You may qualify if:
- Patients must provide written informed consent prior to performance of study-specific procedures or assessments.
- ARID1A Subgroup (N = 39):
- Histologically confirmed locally advanced or metastatic solid tumor malignancy with progression on at least one prior systemic therapy, including one of the following tumor types:
- Renal cell carcinoma with predominant clear cell histology (Cohort A)
- Urothelial carcinoma (Cohort B)
- All pancreatic cancers (Cohort C)
- Other solid tumors excluding clear cell ovarian cancer and endometrial cancer (Cohort D)
- Endometrial and ovarian cancer (Cohort E)
- Formalin-fixed paraffin embedded tumor tissue evaluable for BAF250a expression by ARID1A immunohistochemistry. Primary or metastatic tumor tissue is permissible. Patients without evaluable archival tissue may undergo optional tumor biopsy during Screening if other eligibility criteria have been met
- Measurable disease by RECIST 1.1
- ATM Loss Subgroup (N = 20):
- Histologically confirmed locally advanced or metastatic solid tumor malignancy with progression on at least one prior systemic therapy, including one of the following tumor types:
- Metastatic castration resistant prostate cancer (N = 10).
- Patients may have evaluable or measurable disease by RECIST 1.1 criteria.
- Prior treatment with at least one androgen signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide, darolutamide).
- +42 more criteria
You may not qualify if:
- History of secondary malignancy requiring treatment within 1 year prior to screening, with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, low/intermediate risk localized prostate cancer (=\< Gleason 7, =\< T2N0M0, and prostate-specific antigen (PSA) =\< 20 ng/mL at diagnosis) (not applicable for prostate cancer cohort), ductal carcinoma in situ, Stage I uterine cancer, and non-muscle invasive urothelial carcinoma
- Patients receiving, or having received within 14 days of C1D1, corticosteroids at a dose \> 10 mg/day of prednisone (or equivalent).
- Patients with myelodysplastic syndrome or features suggestive of myelodysplastic syndrome.
- Prior treatment with ATR inhibitor
- Major surgical procedures \< 28 days prior to C1D1. Patients must have recovered to grade =\< 1 for any adverse events related to the surgical procedure.
- Untreated central nervous system (CNS) metastases. Patients with previously treated central nervous system (CNS) metastases are eligible if:
- No requirement for corticosteroids at study entry
- Radiographically and clinically stable for at least 4 weeks prior to study entry
- No evidence of intra-tumoral hemorrhage
- No evidence of current or prior leptomeningeal disease.
- Clinically significant gastrointestinal abnormalities that may increase the risk of decreased absorption of medications, including:
- Inability to swallow oral medications
- Active peptic ulcer disease
- Known intra-luminal metastatic lesions
- History of abdominal fistula or bowel perforation
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Rahul Aggarwallead
- AstraZenecacollaborator
Study Sites (3)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California, San Francisco
San Francisco, California, 94143, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Related Publications (1)
Zhu X, Alvarez EA, Umetsu SE, Chapman JS, Chen LM, Ueda S, Henderson S, Nguyen P, Calabrese S, Russell J, Aguilar J, Smith SA, Shah N, Feeney L, Van Ziffle J, Turski ML, Ko AH, Munster PN, Ashworth A, Collisson EA, Aggarwal RR. Efficacy of the ATR inhibitor ceralasertib in patients with ARID1A-deficient gynecologic and other solid tumor malignancies. Clin Cancer Res. 2026 Feb 13. doi: 10.1158/1078-0432.CCR-25-4043. Online ahead of print.
PMID: 41686845DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rahul Aggarwal, MD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 21, 2018
First Posted
September 24, 2018
Study Start
January 17, 2019
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
March 31, 2028
Last Updated
April 23, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share