An Open-Label Phase 1 Study of Ceralasertib in Japanese Patients With Advanced Solid Malignancies

NCT05469919 | Completed Phase 1

• 1 other identifier: D5330C00014
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label study designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of ceralasertib in Japanese patients with advanced solid malignancies. Cycle 0 duration is 4 days and each cycle from Cycle 1 has a duration of 28 days.

Conditions

Advanced Solid Malignancies

Keywords

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

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)

• 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

• Progression Free Survival

  From start of treatment until the date of objective disease progression or death. (approximately 6 months).

• Plasma ceralasertib concentration(Cmax)

  Cycle 0 Day1 to Day4, Cycle1 Day1 and Cycle 1 Day 7 or Day 8. At the end of Cycle1(each cycle is 28 days)

Study Arms (1)

Ceralasertib monotherapy

EXPERIMENTAL

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

Drug: Ceralasertib

Interventions

Ceralasertib DRUG

Ceralasertib taken orally

Ceralasertib monotherapy

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 of a solid, malignant tumor that is refractory to standard therapies or for which no standard therapies exist.
• Measurable or non-measurable disease according to RECIST version 1.1.
• Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance status of 0 to 1 with no deterioration between screening and the first dose of the study treatment, and a minimum life expectancy of 12 weeks
• Body weight \>30 kg and no cancer-associated cachexia (e.g., common terminology criteria for adverse events \[CTCAE\] Grade 2 or worse weight loss over the past 3 months).

You may not qualify if:

• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting the study treatment, with the exception of alopecia and chemotherapy-related peripheral neuropathy.
• Presence of life-threatening metastatic visceral disease, as judged by the investigator, uncontrolled central nervous system (CNS) metastatic disease. Patients with spinal cord compression and/or brain metastases may be enrolled if definitively treated (e.g., surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start of the study treatment.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B virus \[HBV\], surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
• Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
• Diagnosis of ataxia telangiectasia.
• Past medical history of interstitial lung disease (ILD) / pneumonitis requiring steroid treatment or any evidence of clinically active ILD / pneumonitis or potential ILD / pneumonitis which is not excluded by the screening test.
• Treatment with any of the following:
• Any investigational medicinal product or other systemic anticancer treatment within 4 weeks prior to the first dose of the study treatment, except for immunotherapy or antibody therapy which has five-fold half-life \>4 weeks is within 8 weeks.
• Note: androgen-deprivation therapy is permitted for patients with prostate cancer
• The potent inducers or inhibitors of CYP3A within 2 weeks of the first dose of the study treatment; except for St. John's wort, which is 3 weeks.
• Prior exposure to an ATR inhibitor.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Chūōku, 104-0045, Japan

Location

Related Publications (1)

• Kuboki Y, Matsubara N, Nakajima H, Fujisawa T, Koyama T, Sato J, Katsuya Y, Kmieciak A, Slade D, Iwata K, Takahashi Y, Nii M, Murayama K, Kawata T, Kawasumi H, Yamamoto N. Ceralasertib, an ATR kinase inhibitor, as monotherapy in Japanese patients with advanced solid malignancies: Results from a phase 1 study. Invest New Drugs. 2025 Dec;43(6):1235-1246. doi: 10.1007/s10637-025-01592-x. Epub 2025 Dec 6.

  PMID: 41351730 DERIVED

MeSH Terms

Interventions

ceralasertib

Study Design

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

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: July 22, 2022
• Study Start: June 9, 2022
• Primary Completion: August 17, 2023
• Study Completion: March 12, 2024
• Last Updated: August 2, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• 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 deidentified 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

JP (1)