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Trial record 1 of 1 for:    NCT04082364
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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

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).

Condition or disease Intervention/treatment Phase
Gastric Cancer Gastroesophageal Junction Cancer HER2-positive Gastric Cancer Combination Product: margetuximab plus INCMGA00012 Combination Product: Margetuximab plus INCMGA00012 plus chemo Combination Product: Margetuximab plus MGD013 plus chemo Combination Product: Margetuximab plus chemo Combination Product: Trastuzumab plus chemo Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 860 participants
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
Official Title: 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
Actual Study Start Date : September 30, 2019
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Margetuximab plus INCMGA00012
margetuximab plus INCMGA00012
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

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)
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

Experimental: Margetuximab plus MGD013 plus chemo
margetuximab plus MGD013 plus XELOX or mFOLFOX-6
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

Experimental: Margetuximab plus chemo
margetuximab plus XELOX or mFOLFOX-6
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

Active Comparator: Control Arm
Trastuzumab plus XELOX or mFOLFOX-6
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




Primary Outcome Measures :
  1. 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)

  2. 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)

  3. Overall survival [ Time Frame: Up to 3 years ]
    Time from randomization to death from any cause (Cohort B)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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.



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

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

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): NCT04082364


Contacts
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Contact: Amy Worth 240-660-0757 wortha@macrogenics.com
Contact: Aisha Wynter-Horton 240-552-8069 wynterhortona@Macrogenics.com

Locations
Show Show 30 study locations
Sponsors and Collaborators
MacroGenics
Zai Lab (Shanghai) Co., Ltd.
Investigators
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Study Director: Minori K. Rosales, MD, PhD MacroGenics
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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT04082364    
Other Study ID Numbers: CP-MGAH22-06
First Posted: September 9, 2019    Key Record Dates
Last Update Posted: July 22, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MacroGenics:
gastric cancer
gastroesophageal junction cancer
HER2-positive gastroesophageal cancer
anti-HER2 therapy
checkpoint inhibitors
PD-1
LAG-3
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Trastuzumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs