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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)

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ClinicalTrials.gov Identifier: NCT04305249
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : January 12, 2023
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Antengene Corporation ( Antengene Therapeutics Limited )

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.

Condition or disease Intervention/treatment Phase
Solid Tumor Hematological Malignancy Drug: ATG-017 Drug: ATG-017+Nivolumab Phase 1

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 211 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 15, 2020
Estimated Primary Completion Date : May 20, 2023
Estimated Study Completion Date : August 20, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

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 Name: 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 Name: AZD0364 hemi-adipic acid+Opdivo




Primary Outcome Measures :
  1. AEs/SAEs [ Time Frame: 18 months ]
    Toxicity will be graded according to the NCI CTCAE, Version 5.0.


Secondary Outcome Measures :
  1. Plasma concentrations [ Time Frame: 18 months ]
    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

  2. Overall Response Rate (ORR) [ Time Frame: 18 months ]
    To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006

  3. DOR [ Time Frame: 18 months ]
    Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented

  4. Progression-Free Survival (PFS) [ Time Frame: 18 months ]
    The time from the first dose date until disease progression or death from any cause


Other Outcome Measures:
  1. Level of phospho-p90RSK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of phospho-p90RSK

  2. Level of transcript biomarker [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of DUSP6

  3. Level of phospho-ERK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of phospho-ERK

  4. Level of total ERK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of total ERK



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04305249


Contacts
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Contact: Shimin Sun Sun, M.D. 021-23566665 jasmine.sun@antengene.com
Contact: Leng Julia, M.Sc julia.leng@antengene.com

Locations
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Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
East Melbourne, Victoria, Australia, 3002
Principal Investigator: Ben Tran         
Principal Investigator: Jayesh Desai         
Austin Hospital Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Hui Gan         
Principal Investigator: Hui Gan         
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Mark Voskoboynik         
Principal Investigator: Mark Voskoboynik         
Australia
Scientia Clinical Research Recruiting
Randwick, Australia
Contact: Charlotte Lemech         
Chris O'Brien Lifehouse Recruiting
Sydney, Australia
Contact: Lisa Horvath         
Sponsors and Collaborators
Antengene Therapeutics Limited
Bristol-Myers Squibb
Investigators
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Study Director: Sai Lou, MD Clinical Research Physician
Study Director: Anupa Kudva, MD Clinical Research Physician
Study Director: Yiqiang Zhao, MD Executive Director
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Responsible Party: Antengene Therapeutics Limited
ClinicalTrials.gov Identifier: NCT04305249    
Other Study ID Numbers: ATG-017-001
First Posted: March 12, 2020    Key Record Dates
Last Update Posted: January 12, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action