A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer

NCT04564027 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: D5339C000012024-515102-12-002020-002529-27
• Study Type: interventional
• Target: 54
• Locations: 3 countries
• Sites: 18

Brief Summary

The study is investigating efficacy, safety and tolerability of DNA-damage Response Agents (or Combinations), in participants with advanced/metastatic solid malignancies whose tumours contain molecular alterations

Conditions

Advanced Solid Tumours

Keywords

Ataxia telangiectasia mutated; Metastatic castration-resistant prostate cancer; Rad3-related protein

Outcome Measures

Primary Outcomes (2)

• Cohort A (aST): Objective Response Rate (ORR).

  ORR is defined as the percentage of participants who have at least one response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by response evaluation criteria in solid tumours \[RECIST\] 1.1) that is confirmed at least 4 weeks later. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.

  2 years 4 months

• Cohort B (mCRPC): Composite Response Rate.

  Composite response rate is defined as the investigator assessed radiological response by RECIST 1.1 for soft tissue and visceral lesions and Prostate Cancer Working Group 3 (PCWG3) for bone lesions, confirmed prostate specific antigen (PSA) decline of more than 50%, and/or confirmed circulating tumour cell \[CTC\] conversion from unfavorable (\>=5 cells/7.5 ml blood) to favorable (\<5 cells). Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.

  Up to 2 years 4 months

Secondary Outcomes (5)

• Cohort A (aST): Duration of Radiological Response (DoR)

  Up to 2 years 4 months

• Cohort A (aST): Progression Free Survival (PFS)

  Up to 2 years 4 months

• Cohort A (aST): Percentage Change in Tumor Size

  Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32), 5 (Week 40), 6 (Week (48), 7 (Week 56)

• Cohort B (mRCPC): Percentage Change in Tumor Size

  Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32)

• Cohort A (aST) and B (mCRPC): Number of Participants With Serious and Non-serious Adverse Events

  From Screening (Day -28 to Day -1) Until Follow-up (30 days post last dose), up to 2 years 4 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.

Drug: Ceralasertib

Cohort B

EXPERIMENTAL

Eligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy.

Drug: Ceralasertib

Interventions

Ceralasertib DRUG

Tablets will be administered orally

Also known as: AZD6738

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a histologically confirmed diagnosis of AST (excluding NSCLC) or mCRPC tumour.
• Participants must have a deleterious or suspected deleterious ATM mutation in tumour or blood (germline or ctDNA). Definitions of qualifying ATM mutations may include deleterious/suspected deleterious, pathogenic/likely pathogenic, disease- or cancer-associated variants, or equivalent wording. Variants of unknown significance, benign or likely benign alterations are not qualifying.
• Participant must have normal organ and bone marrow function measured within 28 days prior to the first dose of study intervention.
• Participants who have no curative treatment options and are deemed appropriate for an investigational study in the opinion of the investigator.
• Availability of archival or fresh tumour specimens for central testing of ATM protein loss using immunohistochemistry and for confirmation of ATM mutation using next generation sequencing.
• Previously received and progressed on at least one novel hormonal agent (eg, abiraterone acetate, apalutamide, and/or enzalutamide) for the treatment of prostate cancer
• Participants with histologically confirmed metastatic castrate resistant prostate cancer.
• Documented prostate cancer progression at study entry while on androgen deprivation or after bilateral orchiectomy as assessed by the investigator.
• Serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before enrolment.

You may not qualify if:

• Any of the following cardiac diseases currently or within the last 6 months:
• Unstable angina pectoris.
• Congestive heart failure \> Class 2 as defined by the New York Heart Association
• Acute myocardial infarction.
• Significant ventricular or supraventricular arrhythmias.
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from three electrocardiograms (ECGs) in 24 hours using the Fredericia formula.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age.
• For Cohort B (mCRPC\]), surgery or local prostatic intervention (excluding a prostatic biopsy) within 28 days of Cycle 1 Day 1.
• Participants with known active infections ((i.e., hepatitis B or C, tuberculosis, or COVID-19).
• Participants considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• Participants with symptomatic and/or uncontrolled brain metastases.
• Previous therapy with an telangiectasia and rad3 related protein inhibitor.
• Exposure to a small molecule investigational product within 14 days or 5 half-lives.
• Concomitant use of known strong CYP 3A inhibitors and inducers.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (18)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Los Angeles, California, 90089, United States

Location

Research Site

San Francisco, California, 94115, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Indianapolis, Indiana, 46202, United States

Location

Research Site

Baltimore, Maryland, 21231, United States

Location

Research Site

Ann Arbor, Michigan, 48109, United States

Location

Research Site

Las Vegas, Nevada, 89119, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Ephrata, Pennsylvania, 17522, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Myrtle Beach, South Carolina, 29572, United States

Location

Research Site

Bordeaux, 33076, France

Location

Research Site

Dijon, 21079, France

Location

Research Site

Lyon, 69373, France

Location

Research Site

Vandœuvre-lès-Nancy, 54519, France

Location

Research Site

Barcelona, 08036, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Related Links

• CSP\_redacted
• CSR Synopsis\_redacted
• SAP\_redacted

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies

Interventions

ceralasertib

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

Information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 25, 2020
• Study Start: December 1, 2020
• Primary Completion: February 18, 2025
• Study Completion: February 18, 2025
• Last Updated: August 29, 2025
• Results First Posted: June 25, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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 data in 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

US (12); ES (2); FR (4)