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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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 )

Tracking Information
First Submitted Date  ICMJE March 5, 2020
First Posted Date  ICMJE March 12, 2020
Last Update Posted Date January 12, 2023
Actual Study Start Date  ICMJE August 15, 2020
Estimated Primary Completion Date May 20, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)		 AEs/SAEs [ Time Frame: 18 months ]
Toxicity will be graded according to the NCI CTCAE, Version 5.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • 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
  • Overall Response Rate (ORR) [ Time Frame: 18 months ]
    To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006
  • 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
  • Progression-Free Survival (PFS) [ Time Frame: 18 months ]
    The time from the first dose date until disease progression or death from any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 11, 2020)
  • Level of phospho-p90RSK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of phospho-p90RSK
  • Level of transcript biomarker [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of DUSP6
  • Level of phospho-ERK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of phospho-ERK
  • Level of total ERK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of total ERK
Original Other Pre-specified Outcome Measures
 (submitted: March 10, 2020)
  • Level of phospho-p90RSK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of phospho-p90RSK
  • Level of transcript biomarker [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of DUSP6
  • Level of phospho-ERK and total ERK [ Time Frame: 18 months ]
    Blood samples will be analysed for the level of phospho-ERK and total ERK
 
Descriptive Information
Brief Title  ICMJE Safety and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Advanced Solid Tumors and Hematological Malignancies
Official Title  ICMJE 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
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Hematological Malignancy
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: ATG-017
  • 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.
    Intervention: Drug: ATG-017+Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2023)		 211
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2020)		 60
Estimated Study Completion Date  ICMJE August 20, 2023
Estimated Primary Completion Date May 20, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

    -
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shimin Sun Sun, M.D. 021-23566665 jasmine.sun@antengene.com
Contact: Leng Julia, M.Sc julia.leng@antengene.com
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04305249
Other Study ID Numbers  ICMJE ATG-017-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Antengene Corporation ( Antengene Therapeutics Limited )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Antengene Therapeutics Limited
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Sai Lou, MD Clinical Research Physician
Study Director: Anupa Kudva, MD Clinical Research Physician
Study Director: Yiqiang Zhao, MD Executive Director
PRS Account Antengene Corporation
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP