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

Primary Purpose

Solid Tumor, Hematological Malignancy

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
ATG-017
ATG-017+Nivolumab
Sponsored by
Antengene Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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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Sites / Locations

  • Peter MacCallum Cancer CentreRecruiting
  • Austin HospitalRecruiting
  • Alfred HospitalRecruiting
  • Scientia Clinical ResearchRecruiting
  • Chris O'Brien LifehouseRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Module A (ATG-017 Monotherapy)

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Overall Response Rate (ORR)
To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006
DOR
Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented
Progression-Free Survival (PFS)
The time from the first dose date until disease progression or death from any cause

Full Information

First Posted
March 5, 2020
Last Updated
January 11, 2023
Sponsor
Antengene Therapeutics Limited
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT04305249
Brief Title
Safety and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Advanced Solid Tumors and Hematological Malignancies
Acronym
ERASER
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 15, 2020 (Actual)
Primary Completion Date
May 20, 2023 (Anticipated)
Study Completion Date
August 20, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Antengene Therapeutics Limited
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Hematological Malignancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
211 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Module A (ATG-017 Monotherapy)
Arm Type
Experimental
Arm Description
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.
Arm Title
Module B (ATG-017+Nivolumab Combination Therapy in Solid Tumors)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ATG-017
Other Intervention Name(s)
AZD0364 hemi-adipic acid
Intervention Description
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
Intervention Name(s)
ATG-017+Nivolumab
Other Intervention Name(s)
AZD0364 hemi-adipic acid+Opdivo
Intervention Description
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.
Primary Outcome Measure Information:
Title
AEs/SAEs
Description
Toxicity will be graded according to the NCI CTCAE, Version 5.0.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Plasma concentrations
Description
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
Time Frame
18 months
Title
Overall Response Rate (ORR)
Description
To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006
Time Frame
18 months
Title
DOR
Description
Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented
Time Frame
18 months
Title
Progression-Free Survival (PFS)
Description
The time from the first dose date until disease progression or death from any cause
Time Frame
18 months
Other Pre-specified Outcome Measures:
Title
Level of phospho-p90RSK
Description
Blood samples will be analysed for the level of phospho-p90RSK
Time Frame
18 months
Title
Level of transcript biomarker
Description
Blood samples will be analysed for the level of DUSP6
Time Frame
18 months
Title
Level of phospho-ERK
Description
Blood samples will be analysed for the level of phospho-ERK
Time Frame
18 months
Title
Level of total ERK
Description
Blood samples will be analysed for the level of total ERK
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shimin Sun Sun, M.D.
Phone
021-23566665
Email
jasmine.sun@antengene.com
First Name & Middle Initial & Last Name or Official Title & Degree
Leng Julia, M.Sc
Email
julia.leng@antengene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sai Lou, MD
Organizational Affiliation
Clinical Research Physician
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Anupa Kudva, MD
Organizational Affiliation
Clinical Research Physician
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Yiqiang Zhao, MD
Organizational Affiliation
Executive Director
Official's Role
Study Director
Facility Information:
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ben Tran
First Name & Middle Initial & Last Name & Degree
Jayesh Desai
Facility Name
Austin Hospital
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hui Gan
First Name & Middle Initial & Last Name & Degree
Hui Gan
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Voskoboynik
First Name & Middle Initial & Last Name & Degree
Mark Voskoboynik
Facility Name
Scientia Clinical Research
City
Randwick
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlotte Lemech
Facility Name
Chris O'Brien Lifehouse
City
Sydney
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Horvath

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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