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Combination Margetuximab, INCMGA00012, MGD013, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer (MAHOGANY)

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ClinicalTrials.gov Identifier: NCT04082364
Recruitment Status : Recruiting
First Posted : September 9, 2019
Last Update Posted : July 22, 2020
Sponsor:
Collaborator:
Zai Lab (Shanghai) Co., Ltd.
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE September 5, 2019
First Posted Date  ICMJE September 9, 2019
Last Update Posted Date July 22, 2020
Actual Study Start Date  ICMJE September 30, 2019
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2020)
  • Incidence of Adverse Events of margetuximab plus INCMGA00012 as assessed by CTCAE v5.0 [ Time Frame: 6 month intervals ]
    Evaluation of adverse events and serious adverse events (Cohort A)
  • Objective response rate (ORR) for non-microsatellite instability-high (non-MSI-H) patients (Cohort A) [ Time Frame: 3 years ]
    Proportion of non MSI-H patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A and B)
  • Overall survival [ Time Frame: Up to 3 years ]
    Time from randomization to death from any cause (Cohort B)
Original Primary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
  • Incidence of Adverse Events of margetuximab plus INCMGA00012 as assessed by CTCAE v5.0 [ Time Frame: 6 month intervals ]
    Evaluation of adverse events and serious adverse events (Cohort A)
  • Objective response rate (ORR) [ Time Frame: 3 years ]
    Proportion of patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A and B)
  • Overall survival [ Time Frame: Up to 3 years ]
    Time from randomization to death from any cause (Cohort B)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2019)
  • Progression-free survival [ Time Frame: Up to 3 years ]
    Time from start of study treatment to the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. (Cohorts A and B)
  • Duration of response [ Time Frame: Up to 3 years ]
    Time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first (Cohorts A and B)
  • Disease control rate [ Time Frame: Up to 3 years ]
    Percentage of patients who experienced response of CR, PR or stable disease for at least 3 months from start of study treatment (Cohorts A and B)
  • Patient reported quality of life [ Time Frame: Up to 3 years ]
    Quality of life as assessed using the Functional Assessment of Cancer Therapy - Gastric Questionnaire (FACT-Ga) (Cohort B) on a scale of 0 to 184. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
  • Progression-free survival [ Time Frame: Up to 3 years ]
    Time from start of study treatment to the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. (Cohorts A and B)
  • Duration of response [ Time Frame: Up to 3 years ]
    Time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first (Cohorts A and B)
  • Disease control rate [ Time Frame: Up to 3 years ]
    Percentage of patients who experienced response of CR, PR or stable disease for at least 3 months from start of study treatment (Cohorts A and B)
  • Patient reported quality of life [ Time Frame: Up to 3 years ]
    Quality of life as assessed using the Functional Assessment of Cancer Therapy - Gastric Questionnaire (FACT-Ga) (Cohort B)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Margetuximab, INCMGA00012, MGD013, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer (MAHOGANY)
Official Title  ICMJE Phase 2/3 Trial to Evaluate Margetuximab in Combination With INCMGA00012 and Chemotherapy or MGD013 and Chemotherapy in Patients With Metastatic or Locally Advanced, Treatment-naïve, HER2-Positive Gastric or Gastroesophageal Junction Cancer
Brief Summary This is a Phase 2/3, randomized, open-label study for the treatment of patients with HER2-positive Gastric cancer (GC) or Gastroesophageal Junction (GEJ) cancer to determine the efficacy of margetuximab combined with INCMGA00012 (also known as MGA012) (Cohort A) and margetuximab combined with INCMGA00012 or MGD013 and chemotherapy compared to trastuzumab combined with chemotherapy (Cohort B).
Detailed Description A single-arm cohort (Cohort A, 40 to 110 patients) will evaluate safety and efficacy of margetuximab plus INCMGA00012. In a 4-arm cohort (Cohort B Part 1, 50 patients per arm), patients will be randomized to margetuximab plus chemotherapy plus INCMGA00012, margetuximab plus chemotherapy plus MGD013, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy. A checkpoint inhibitor (CPI) (INCMGA00012 or MGD013) will be selected from Cohort B Part 1 and evaluated in a randomized 2-arm cohort (Cohort B Part 2, 250 patients per arm) of margetuximab plus chemotherapy plus INCMGA00012 or MGD013, or trastuzumab plus chemotherapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Cohort A is a single-arm cohort to evaluate safety and efficacy of margetuximab plus INCMGA00012. Cohort B Part 1 is a randomized, 4-arm segment to evaluate margetuximab plus INCMGA00012 plus chemotherapy, margetuximab plus MGD013 plus chemotherapy, margetuximab plus chemotherapy, vs trastuzumab plus chemotherapy. Cohort B Part 2 is a randomized, 2-arm segment to evaluate margetuximab plus the selected checkpoint inhibitor from Part 1, plus chemotherapy vs. trastuzumab plus chemotherapy.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastric Cancer
  • Gastroesophageal Junction Cancer
  • HER2-positive Gastric Cancer
Intervention  ICMJE
  • Combination Product: margetuximab plus INCMGA00012

    margetuximab: Fc-modified anti-HER2 monoclonal antibody:

    • 15 mg/kg IV Day1 of each 3 week cycle

    INCMGA00012: anti-PD-1 checkpoint inhibitor:

    • 375 mg IV Day 1 of each 3 week cycle

    Other Names:
    • MGAH22
    • MGA012
  • Combination Product: Margetuximab plus INCMGA00012 plus chemo

    margetuximab: Fc-modified anti-HER2 monoclonal antibody

    • 15 mg/kg IV Day1 of each 3 week cycle

    INCMGA00012: anti-PD-1 checkpoint inhibitor

    • 375 mg IV Day 1 of each 3 week cycle

    Chemotherapy

    • Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy
    • Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy
    • Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6
    • Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    Other Names:
    • MGAH22
    • MGA012
  • Combination Product: Margetuximab plus MGD013 plus chemo

    margetuximab: Fc-modified anti-HER2 monoclonal antibody

    • 15 mg/kg IV Day1 of each 3 week cycle

    MGD013: Anti-PD-1, anti-LAG-3 dual checkpoint inhibitor DART molecule

    • Dosing regimen located in the protocol

    Chemotherapy

    • Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy
    • Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy
    • Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6
    • Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    Other Name: MGAH22
  • Combination Product: Margetuximab plus chemo

    margetuximab: Fc-modified anti-HER2 monoclonal antibody

    • 15 mg/kg IV Day1 of each 3 week cycle

    Chemotherapy

    • Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy
    • Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy
    • Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6
    • Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    Other Name: MGAH22
  • Combination Product: Trastuzumab plus chemo

    Anti-HER2 monoclonal antibody

    • 8 mg/kg loading dose and then 6 mg/kg administered IV on Day 1 of each 3 week cycle

    Chemotherapy

    • Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy
    • Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy
    • Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    • Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6
    • Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
    Other Name: Herceptin
Study Arms  ICMJE
  • Experimental: Margetuximab plus INCMGA00012
    margetuximab plus INCMGA00012
    Intervention: Combination Product: margetuximab plus INCMGA00012
  • Experimental: Margetuximab plus INCMGA00012 plus chemo
    margetuximab plus INCMGA00012 plus capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
    Intervention: Combination Product: Margetuximab plus INCMGA00012 plus chemo
  • Experimental: Margetuximab plus MGD013 plus chemo
    margetuximab plus MGD013 plus XELOX or mFOLFOX-6
    Intervention: Combination Product: Margetuximab plus MGD013 plus chemo
  • Experimental: Margetuximab plus chemo
    margetuximab plus XELOX or mFOLFOX-6
    Intervention: Combination Product: Margetuximab plus chemo
  • Active Comparator: Control Arm
    Trastuzumab plus XELOX or mFOLFOX-6
    Intervention: Combination Product: Trastuzumab plus chemo
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: June 15, 2020)
860
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2019)
850
Estimated Study Completion Date  ICMJE May 2026
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma

    1. Prior systemic perioperative treatment is allowed; however the patient must have had a disease-free interval of at least 6 months from end of chemo/surgery
    2. Patients receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility
    3. Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%) per central review
    4. Cohort B: HER2-positive (by IHC 3+ or IHC 2+ in combination with FISH+) by local review. PD -L1 status is not required for enrollment.
  • Availability of formalin-fixed, paraffin-embedded tumor specimen, unstained slides or contemporaneous biopsy for tumor target testing
  • Eastern Cooperative Oncology Group performance status of 0 or 1, verified within 3 days of Day 1
  • Life expectancy ≥ 6 months
  • At least one radiographically measurable target lesion
  • Acceptable laboratory parameters and adequate organ function

Key Exclusion Criteria:

  • Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions

    • Patients with known MSI-H status
  • History of allogeneic stem cell or tissue/solid organ transplant
  • Central nervous system metastases
  • Clinically significant cardiovascular disease, gastrointestinal disorders, pulmonary compromise

    • Prior neoadjuvant or adjuvant treatment with immunotherapy
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: Amy Worth 240-660-0757 wortha@macrogenics.com
Contact: Aisha Wynter-Horton 240-552-8069 wynterhortona@Macrogenics.com
Listed Location Countries  ICMJE Korea, Republic of,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04082364
Other Study ID Numbers  ICMJE CP-MGAH22-06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Zai Lab (Shanghai) Co., Ltd.
Investigators  ICMJE
Study Director: Minori K. Rosales, MD, PhD MacroGenics
PRS Account MacroGenics
Verification Date July 2020

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