Safety and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Advanced Solid Tumors and Hematological Malignancies

NCT ID: NCT04305249

Last Updated: 2024-07-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-15
• Study Completion Date: 2024-05-24

Brief Summary

This is a Phase I, multi-center, open-label study of ATG-017 administered orally, alone or in combination with nivolumab in patients with advanced solid tumors and hematological malignancies. The study is composed of two modules: ATG-017 monotherapy (Module A) and ATG-017 in combination with nivolumab (Module B). Both Modules A and B will include Dose Escalation Phase and Dose Expansion Phase.

Detailed Description

The dose escalation of ATG 017 will be conducted with intensive safety monitoring to ensure the safety of the patients with solid tumors (Module A and Module B) and hematological malignancies (Module A) harbouring activating alterations in the RAS-MAPK pathway, and will include the continuous and intermittent dosing schedules.

The Dose Expansion Phase will start based on dose level and schedule (continuous or intermittent)

Conditions

Solid Tumor; Hematological Malignancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Module A (ATG-017 Monotherapy)

Dosing will begin at 5 mg QD ATG-017 as starting dose. A treatment cycle will be 21 days for continuous dosing and 28 days for 7 days on/7 days off intermittent dosing of ATG-017 treatment.

Group Type: EXPERIMENTAL

ATG-017

Intervention Type: DRUG

Dosing will begin at 5 mg QD ATG-017 as starting dose. A treatment cycle will be 21 days for continuous dosing and 28 days for 7 days on/7 days off intermittent dosing of ATG-017 treatment.

Module B (ATG-017+Nivolumab Combination Therapy in Solid Tumors)

With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be given at fixed dosing, 480 mg Q4W, on D1 of each cycle.

Group Type: EXPERIMENTAL

ATG-017+Nivolumab

Intervention Type: DRUG

With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be specified dose on specified days.

Interventions

ATG-017

Dosing will begin at 5 mg QD ATG-017 as starting dose. A treatment cycle will be 21 days for continuous dosing and 28 days for 7 days on/7 days off intermittent dosing of ATG-017 treatment.

Intervention Type: DRUG

ATG-017+Nivolumab

With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be specified dose on specified days.

Intervention Type: DRUG

Other Intervention Names

AZD0364 hemi-adipic acid; AZD0364 hemi-adipic acid+Opdivo

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

2. Aged at least 18 years.

3. Module A: Patient must have a documented activating alteration of the RAS-MAPK pathway.

4. Module B: Dose Escalation Phase: Patient must have a documented activating alteration of the RAS-MAPK pathway; Dose Expansion Phase: Expansion cohorts will be further defined based on information from the Dose Escalation.

5. Histological or cytological confirmation of a solid tumour.

6. Patient with solid tumors must have at least 1 lesion, not previously irradiated.

7. Estimated life expectancy of minimum of 12 weeks.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

9. Ability to swallow and retain oral medication.

Exclusion Criteria

1. Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.

2. Prior ATG-017 administration in the present study.

3. Prior treatment with an ERK1/2 inhibitor.

4. Prior major surgery within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.

5. Patients receiving unstable or increasing doses of corticosteroids.

6. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.

7. Active infection including hepatitis B, and/or hepatitis C.

8. Known history of human immunodeficiency virus (HIV) infection.

9. Inadequate bone marrow reserve or organ function

-

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Antengene Therapeutics Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sai Lou, MD

Role: STUDY_DIRECTOR

Clinical Research Physician

Anupa Kudva, MD

Role: STUDY_DIRECTOR

Clinical Research Physician

Yiqiang Zhao, MD

Role: STUDY_DIRECTOR

Executive Director

Locations

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Scientia Clinical Research

Randwick, , Australia

Chris O'Brien Lifehouse

Sydney, , Australia

Countries

Australia

Other Identifiers

ATG-017-001

Identifier Type: -

Identifier Source: org_study_id