A Phase I, Open-Label, Multi-Center, Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG-018 (ATR Inhibitor) Treatment in Patients With Advanced Solid Tumors and Hematological Malignancies

Antengene Discovery Limited5 sites in 1 country22 target enrollmentJuly 8, 2022

ConditionsAdvanced Solid Tumors Hematological Malignancies

InterventionsATG-018

DrugsATG-018

Overview

Phase: Phase 1
Intervention: ATG-018
Conditions: Advanced Solid Tumors
Sponsor: Antengene Discovery Limited
Enrollment: 22
Locations: 5
Primary Endpoint: AE/SAE
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase I, Open-Label, Multi-Center, Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG-018 (ATR inhibitor) Treatment in Patients with Advanced Solid Tumors and Hematological Malignancies .

Detailed Description

This is a Phase I, multi-center, open-label study of ATG-018 administered orally as monotherapy in patients with advanced solid tumors and hematological malignancies. The study design includes a Dose Escalation Phase and a Dose Expansion Phase.

Registry

clinicaltrials.gov

Start Date

July 8, 2022

End Date

January 8, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Antengene Discovery Limited

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects must meet all the following inclusion criteria to be eligible to enroll in this study:
•Provision of signed and dated, written informed consent prior to any study specific procedures, sampling, and analyses.
•Aged at least 18 years.
•After completion of Dose level 3, subjects will need to demonstrate a defect in one or more DDR genes such as: ATM (including ATM protein loss by IHC), ATRX, ARID1A, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, MSH2, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, or other related genes at the discretion of the investigator in consultation with sponsor Medical Monitor; Or mutations in p53 pathway/MYC pathway.
•Subjects with solid tumor must meet the following criteria: histological or cytological confirmation of a solid tumor, and have progressed despite standard therapy(ies), or are intolerant to standard therapy(ies), or have a tumor for which no standard therapy(ies) exists. Locally recurrent disease must not be amenable to surgical resection or radiotherapy with curative intent (subjects who are considered suitable for surgical or ablative techniques following down-staging with study treatment are not eligible).
•Subjects with hematological malignancies must meet the following criteria: have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (eg, follicular lymphoma) or B-cell indolent Non-Hodgkin's Lymphoma (iNHL) with histological subtype limited to FL Grade 1, Grade 2, or Grade 3a, or Grade 3b, or splenic marginal zone lymphoma (MZL), or nodal MZL, or extranodal MZL based on criteria established by the World Health Organization (WHO) 2016 classification.
•Subjects with DLBCL must have received at least 2 previous systemic regimens for the treatment of their de novo or transformed DLBCL including at least 1 course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine, or gemcitabine must have been given) combined with at least 1 course of anti-CD20 immunotherapy (eg, rituximab), unless contraindicated due to severe toxicity. Prior stem cell transplantation was allowed; induction, consolidation, stem cell collection, preparative regimen, and transplantation ± maintenance were considered a single line of therapy.
•Subjects with B-cell iNHL must have received at least one previous line of therapy including a CD20-targeted monoclonal antibody, and systemic therapy does not include local involved field radiotherapy for limited stage disease and/or H. Pylori eradication.
•Please note that all hematological malignancies must have documented clinical or radiographic evidence of progressive prior to dosing.
•Subjects must have measurable lesion defined as below:

Exclusion Criteria

•Subjects meeting any of the following exclusion criteria are not eligible to enroll in this study:
•Central nervous system (CNS) metastatic disease, leptomeningeal disease, or metastatic cord compression.
•Prior treatment with ATR inhibitor.
•Subjects with B-NHL in the condition as below:
•DLBCL with MALT lymphoma.
•Composite lymphoma (Hodgkin's lymphoma + NHL).
•Primary mediastinal (thymic) large B-cell lymphoma.
•Prior therapy with any other investigational product or anticancer systemic therapy including chemotherapy, immunotherapy, or other anticancer agents within 21 days (or within a period during which the investigational product or systemic anticancer treatment has not been cleared from the body, eg, a period of 5 'half-lives') of the first dose of study treatment, whichever is the most appropriate as judged by the investigator.
•Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first dose of study treatment. Subject must have recovered from all radiation related toxicity, not requiring corticosteroids.
•Prior major surgery (excluding placement of vascular access) within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days. No waiting is required following implantable port and catheter placement.

Arms & Interventions

ATG-018

Dose Escalation Phase: For Solid Tumors Group: A maximum of 44 subjects with solid tumors will be enrolled during the Dose Escalation Phase. For Hematological Malignancies Group: Subjects with hematological malignancy will be enrolled. Dose Expansion Phase: The tumor types in Dose Expansion Phase may involve other tumor types based on the signals from the Dose Escalation Phase. Each tumor type is planned to enroll at least 12 subjects, and a further expansion (up to 40 subjects in each tumor type) may be triggered if 2 or more confirmed responses are observed in this cohort.

Intervention: ATG-018