A Study of ATG-018 (ATR Inhibitor) Treatment in Patients With Advanced Solid Tumors and Hematological Malignancies

NCT05338346 | Terminated Phase 1

• 1 other identifier: ATG-018-001
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

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 .

Conditions

Advanced Solid Tumors; Hematological Malignancies

Outcome Measures

Primary Outcomes (3)

• AE/SAE

  Adverse Event/Serious Adverse Event

  12 months after the last subject enrolled

• MTD

  Maximum Tolerated Dose

  12 months after the last subject enrolled

• RP2D

  RP2D= Recommended Phase 2 Dose

  12 months after the last subject enrolled

Secondary Outcomes (2)

• ORR

  12 months after the last subject enrolled

• DOR

  12 months after the last subject enrolled

Other Outcomes (2)

• PFS

  12 months after the last subject enrolled

• OS

  12 months after the last subject enrolled

Study Arms (1)

ATG-018

EXPERIMENTAL

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.

Drug: ATG-018

Interventions

ATG-018 DRUG

Dose Escalation Phase: For both dose escalation groups, subjects will receive a single dose of ATG-018 monotherapy on Cycle 1 Day 1 (C1D1) for single dose PK samples' collection. From the morning dose on Cycle 1 Day 2, twice daily dosing (except Dose Level 1: 5 mg QD) will be initiated. Subject(s) will receive intermittent dosing in a 3 days on/4 days off schedule in 21-day cycles until disease progression or unacceptable toxicity. Dose Expansion Phase : Dose Expansion Phase will begin at the defined MTD/RP2D for solid tumors and hematological malignancies groups, to further evaluate the safety, tolerability, and PDx profile of ATG-018. Subjects with solid tumors and hematological malignancies will be enrolled.

ATG-018

Eligibility Criteria

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

You may qualify if:

• 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:
• Subject with solid tumors must have at least 1 lesion, not previously irradiated, that can be accurately measured at pre dose as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with CT or MRI and which is suitable for accurate repeated measurements.
• Subject with B-NHL must have measurable disease as defined by at least one bi-dimensionally measurable lesion that node \>1.5 cm in longest diameter (LDi) or extranodal lesion \>1 cm in LDi (per the Lugano 2014 Criteria).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration over the previous 2 weeks, or prior to the first dose of study treatment (C1D1).
• Except for hearing loss, alopecia, and pigmentation, all toxicity caused by previous antitumor therapy has recovered to Grade 1 or less (according to the NCI-CTCAE version 5.0).
• Life expectancy \>3 months.
• Men and women of childbearing potential must agree to use effective contraceptives from they sign the informed consent to 180 days after the last dose of study drug. Women of childbearing potential include premenopausal women and women within 2 years after menopause. Women of childbearing age must have a negative serum pregnancy test at screening.

You may not qualify if:

• 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.
• Subjects receiving unstable or increasing doses of corticosteroids. For patients receiving corticosteroids for endocrine deficiencies or symptoms associated to their disease (excluding central nervous system disease), the dose must have been stabilized (or reducing) for at least 14 days before the first dose of study treatment.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension defined as a blood pressure (BP) ≥150/95 mmHg despite medical therapy, unstable or uncompensated respiratory and renal disease, active bleeding diseases, allogeneic stem cell transplantation, or any solid organ transplant.
• Have active or previous autoimmune diseases that are likely to recur (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, and psoriasis), or are at risk of such diseases.
• Active infection including hepatitis B, and/or hepatitis C (HBV-DNA or HCV-RNA detected above lower limit of normal \[LLN\] by local laboratory, respectively).
• Known history of human immunodeficiency virus (HIV) infection.
• Active infection requiring parenteral antibiotics, antivirals, or antifungals within 14 days prior to C1D1; however, prophylactic use of these agents is acceptable (including parenteral).

Sponsors & Collaborators

• Antengene Discovery Limited: lead

Study Sites (5)

Icon Cancer Centre South Brisbane

Brisbane, Australia

Location

Chris O'Brien Lifehouse

Camperdown, Australia

Location

Austin Health

Heidelberg, Australia

Location

Alfred Health

Melbourne, Australia

Location

Liverpool Hospital

Sydney, Australia

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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: April 14, 2022
• First Posted: April 21, 2022
• Study Start: July 8, 2022
• Primary Completion: January 8, 2024
• Study Completion: January 8, 2024
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

AU (5)