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

A Phase I, Open-Label, Multi-Center Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Patients With Advanced Solid Tumors and Hematological Malignancies

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Hematological Malignancy
• Intervention / Treatment: Drug: ATG-017; Drug: ATG-017+Nivolumab

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)

• Study Type: Interventional
• Enrollment (Estimated): 211
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ashley Liu; Phone Number: 021-23566665; Email: ting.liu@antengene.com
• Study Contact Backup: Name: Ran Wei; Email: ran.wei@antengene.com

Study Locations

• Australia
  • Randwick, Australia
    • Recruiting
    • Scientia Clinical Research
    • Contact: Charlotte Lemech
  • Sydney, Australia
    • Recruiting
    • Chris O'Brien Lifehouse
    • Contact: Lisa Horvath
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Recruiting
      • Peter MacCallum Cancer Centre
      • Principal Investigator: Jayesh Desai
      • Principal Investigator: Ben Tran
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Hospital
      • Contact: Hui Gan
      • Principal Investigator: Hui Gan
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Hospital
      • Principal Investigator: Mark Voskoboynik
      • Contact: Mark Voskoboynik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.; Other Names: AZD0364 hemi-adipic acid
Experimental: 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.	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.; Other Names: AZD0364 hemi-adipic acid+Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs/SAEs	Toxicity will be graded according to the NCI CTCAE, Version 5.0.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR	Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented	18 months
Plasma concentrations	Venous blood samples for determination of total concentrations of ATG 017 in plasma to characterise the PK profile of ATG-017 for a particular dose level	18 months
Overall Response Rate (ORR)	To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006	18 months
Progression-Free Survival (PFS)	The time from the first dose date until disease progression or death from any cause	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of phospho-p90RSK	Blood samples will be analysed for the level of phospho-p90RSK	18 months
Level of transcript biomarker	Blood samples will be analysed for the level of DUSP6	18 months
Level of phospho-ERK	Blood samples will be analysed for the level of phospho-ERK	18 months
Level of total ERK	Blood samples will be analysed for the level of total ERK	18 months

Collaborators and Investigators

• Sponsor: Antengene Therapeutics Limited
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Sai Lou, MD, Clinical Research Physician; Study Director: Anupa Kudva, MD, Clinical Research Physician; Study Director: Yiqiang Zhao, MD, Executive Director

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2020
• Primary Completion (Actual): February 29, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: ATG-017-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No