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

NCT04305249 | Terminated Phase 1 DMC

• 1 other identifier: ATG-017-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

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.

Conditions

Solid Tumor; Hematological Malignancy

Outcome Measures

Primary Outcomes (1)

• AEs/SAEs

  Toxicity will be graded according to the NCI CTCAE, Version 5.0.

  18 months

Secondary Outcomes (4)

• Plasma concentrations

  18 months

• Overall Response Rate (ORR)

  18 months

• DOR

  18 months

• Progression-Free Survival (PFS)

  18 months

Other Outcomes (4)

• Level of phospho-p90RSK

  18 months

• Level of transcript biomarker

  18 months

• Level of phospho-ERK

  18 months

Study Arms (2)

Module A (ATG-017 Monotherapy)

EXPERIMENTAL

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.

Drug: ATG-017

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

EXPERIMENTAL

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.

Drug: ATG-017+Nivolumab

Interventions

ATG-017 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.

Also known as: AZD0364 hemi-adipic acid

Module A (ATG-017 Monotherapy)

ATG-017+Nivolumab 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.

Also known as: AZD0364 hemi-adipic acid+Opdivo

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

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.
• Module A: Patient must have a documented activating alteration of the RAS-MAPK pathway.
• 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.
• Histological or cytological confirmation of a solid tumour.
• Patient with solid tumors must have at least 1 lesion, not previously irradiated.
• Estimated life expectancy of minimum of 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Ability to swallow and retain oral medication.

You may not qualify if:

• Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
• Prior ATG-017 administration in the present study.
• Prior treatment with an ERK1/2 inhibitor.
• Prior major surgery within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.
• Patients receiving unstable or increasing doses of corticosteroids.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.
• Active infection including hepatitis B, and/or hepatitis C.
• Known history of human immunodeficiency virus (HIV) infection.
• Inadequate bone marrow reserve or organ function

Sponsors & Collaborators

• Antengene Therapeutics Limited: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Scientia Clinical Research

Randwick, Australia

Location

Chris O'Brien Lifehouse

Sydney, Australia

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Sai Lou, MD

  Clinical Research Physician

  STUDY DIRECTOR

• Anupa Kudva, MD

  Clinical Research Physician

  STUDY DIRECTOR

• Yiqiang Zhao, MD

  Executive Director

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 12, 2020
• Study Start: August 15, 2020
• Primary Completion: April 11, 2024
• Study Completion: May 24, 2024
• Last Updated: July 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)