Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Solid Tumors

Running, not enrolling · Phase 2

Conditions studied: Clear Cell Renal Cell Carcinoma, Locally Advanced Pancreatic Cancer, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Metastatic Renal Cell Carcinoma, Metastatic Urothelial Carcinoma, Metastatic Pancreatic Cancer, Stage III Pancreatic Cancer, Stage III Renal Cell Cancer, Stage IV Pancreatic Cancer, Stage IV Renal Cell Cancer, Endometrial Cancer, Metastatic Castration-resistant Prostate Cancer

In brief

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.

Key facts

Study ID

NCT03682289

Run by

Rahul Aggarwal

People needed

83

Starts

2019-01-17

Expected to finish

2028-03-31

Last updated by the study team

2026-04-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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).
• Patients will be required to maintain castrate levels of testosterone during study treatment with use of Luteinizing hormone-releasing hormone (LHRH) analog (except for patients with history of bilateral orchiectomy).
• Progression by PCWG3 criteria at study entry
• All other solid tumor malignancies (N = 10). Patients are required to have measurable soft tissue disease by RECIST 1.1 criteria.
• Archival tumor tissue evaluable for ATM expression by immunohistochemistry (IHC)
• Evidence of ATM loss by either pathogenic ATM mutation in Chemiluminescent immunoassay (CLIA)-approved assay and/or loss of ATM expression by IHC (Ventana Ab). An interim analysis will be performed after 10 patients are enrolled. If less than 50% of tumors have absence of ATM expression by IHC, subsequent enrollment of the remaining 10 patients will be required to have evidence of both ATM mutation and loss of ATM expression (< 5% of tumor cells expressing ATM) using CLIA-certified IHC test (Ventana).
• Endometrial Cancer Cohort (N = 30):
• Histologically confirmed endometrial cancer
• o A minimum of 15 patients must have the presence of pathogenic ARID1A alteration on CLIA-approved next-generation sequencing panel without evidence of microsatellite instability defined by next-generation sequencing and/or presence of intact mismatch repair proteins by immunohistochemistry.
• Measurable disease by RECIST 1.1.
• Availability of archival tumor tissue for retrospective testing of BAF250a expression by IHC.

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
• History of bowel obstruction within 6 months prior to study entry
• Known malabsorption syndrome
• Significant resection of the small bowel.
• Fridericia's QT correction formula (QTcF) > 470 ms (females) or > 450 ms (males) on screening electrocardiography (ECG), or immediate family history of congenital long QT syndrome or sudden cardiac death at age less than 40.
• History of any one or more of the following cardiovascular conditions within the past 6 months:
• Myocardial infarction
• Unstable angina
• Transient ischemic attack or cerebrovascular accident
• Uncontrolled arrhythmia. Rate controlled atrial fibrillation/flutter is not an exclusion for the study.
• Class III or IV congestive heart failure or documented left ventricle (LV) ejection fraction of < 50% (screening not required).

Where it is running

• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• University of California, San Francisco — San Francisco, California, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States

Full record on ClinicalTrials.gov

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