Human ADME Study of [14C]-Ceralasertib (AZD6738) and Absolute Bioavailability of Ceralasertib

A Phase I, Open-label Study to Assess the Absolute Bioavailability of Ceralasertib (AZD6738) and Absorption, Distribution, Metabolism, and Excretion (ADME) of [14C]-Ceralasertib in Patients With Non-small Cell Lung Cancer, Ovarian Cancer, or Endometrial Cancer

This is an open-label, two-part study in participants with NSCLC, ovarian cancer, or endometrial cancer and will be conducted at multiple study sites.

Participants will be assessed for study eligibility prior to admission to the study site.

Part A will assess the absolute bioavailability, determine the excretory routes of [14C]-Ceralasertib, and evaluate the PK parameters of a Ceralasertib oral dose and a radiolabelled IV microdose of [14C]-Ceralasertib.

Participants will be admitted to the study site pre-dose Part A and will remain at the study site for excreta (urine and faeces) collections, PK sampling and safety assessments. A washout period days will be observed between dosing in Part A and Part B. Part B will assess the ADME of [14C]-Ceralasertib.

Participants will be readmitted to the study site for Part B and will remain at the study site for excreta (urine, faeces, and any vomitus) collections, PK sampling, and safety assessments.

Participants will return to the study site for a Follow-up Visit after the last dose of Ceralasertib which will include routine safety assessments.

After the completion of Parts A and B, and following the Follow-up Visit, participants may be allowed further access to Ceralasertib if in the opinion of the investigator and medical monitor they may derive clinical benefit.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoplasm
• Intervention / Treatment: Drug: [14C] AZD6738; Drug: AZD6738 / ceralasertib

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L7 8YA
    • Research Site
  • London, United Kingdom, NW1 2PG
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants are eligible to be included in the study only if all of the following criteria apply:

Age

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.

   Type of Participant and Disease Characteristics

2. Sufficient ECOG performance status, life expectancy, and ability to swallow and retain oral medication
3. Adequate organ and marrow function
4. Willingness and ability to comply with study and follow-up procedures.
5. Able and willing to stay in hospital for specified residential periods following administration of Ceralasertib/[14C]-Ceralasertib
6. Regular bowel movements
7. Participants with NSCLC must have appropriately documented NSCLC diagnosis, mutation status, treatment history, and disease status according to protocol-specified eligibility criteria
8. Participants with Ovarian cancer must have appropriately documented ovarian cancer diagnosis, mutation status, treatment history, and disease status according to protocol-specified eligibility criteria 9. Participants with Endometrial cancer must have appropriately documented endometrial cancer diagnosis, treatment history, and disease status according to protocol-specified eligibility criteria 10. Sex and Contraceptive/Barrier Requirements: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 11. Informed Consent: patient must be capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

• Participants are excluded from the study if any of the following criteria apply:

  1. History of Diagnosis of protocol-specified medical conditions
  2. Spinal cord compression or brain metastasis prior to start of study intervention unless asymptomatic and stable
  3. Persistent toxicities (CTCAE Grade ≥ 2), with the exception of alopecia and vitiligo, caused by previous anticancer therapy.
  4. History of allogenic organ transplant or autoimmune or inflammatory disorders requiring use of immunosuppressive medications with some protocol specified conditions/exceptions
  5. Any medical or surgical condition that would preclude adequate absorption of Ceralasertib
  6. Inadequate cardiac function / status or other cardiovascular diseases
  7. Participants with active infection requiring systemic antibiotics, antifungal or antiviral drugs
  8. Any evidence of severe or uncontrolled systemic disease, as judged by the investigator that would make it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol
  9. Protocol-specified prior/concomitant therapy exclusions
  10. Protocol-specified prior/concurrent clinical study experience
  11. Other Exclusions including but not limited to tobacco/nicotine and/or alcohol use, or drug/alcohol abuse history
  12. Not currently pregnant, breast-feeding, or planning to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Treatment Arm - AZD6738; Part A - oral dose of Ceralasertib and a radiolabelled IV microdose of [14C]-Ceralasertib Part B - oral dose of [14C]-Ceralasertib	Drug: [14C] AZD6738; radiolabeled AZD6738 / ceralasertib; Drug: AZD6738 / ceralasertib; Ceralasertib (AZD6738) is a potent, selective inhibitor of the serine/threonine-specific protein kinase ATR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate absolute bioavailability Ceralasertib and PK of Ceralasertib and [14C]-Ceralasertib after administration of oral dose of Ceralasertib and IV [14C]-Ceralasertib (Part A	Absolute bioavailability (F) of Ceralasertib and PK parameters	Through end of Part A, approximately 5 weeks including screening period
To determine the rates and major excretory routes of Ceralasertib and its metabolites after IV dose of [14C]-Ceralasertib (Part A) and a oral dose of [14C]-Ceralasertib (Part B)	[14C]-Ceralasertib (Part A) or total radioactivity (Part B) recovery in urine and faeces	Through end of Part B, approximately 10 weeks including screening period
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	AUCinf	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	AUClast	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	Cmax	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	tmax	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	t1/2(lambda)z	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	Ratio of AUCinf of plasma Ceralasertib relative to AUCinf of plasma total radioactivity	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	Ratio of AUCinf of whole blood total radioactivity relative to AUCinf of plasma total radioactivity	Through end of the part B, approximately 10 weeks (Including screening period)
To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B)	Pharmacokinetic activity of ceralasertib present in urine	Through end of the part B, approximately 10 weeks (Including screening period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To provide biologic samples for metabolic profiling and identification after oral dose of [14C]-Ceralasertib (Part B)	Quantification and identification of major metabolites of Ceralasertib in plasma and excreta (will be reported separately)	Through end of the part B, approximately 10 weeks (Including screening period)
To assess the safety of Ceralasertib in participants with NSCLC, ovarian cancer, or endometrial cancer (Parts A and B)	Incidence and severity of AEs Incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results 12-lead ECG parameters Vital signs measurements Physical examinations	Through study completion, approximately 9 - 11 weeks, with screening included

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): January 17, 2025
• Primary Completion (Estimated): August 8, 2025
• Study Completion (Estimated): August 8, 2025

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: endometrial cancer; non-small cell lung cancer; ovarian cancer; AZD6738; ceralasertib; hADME, bioavailability
• Other Study ID Numbers: D533BC00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No