Purpose

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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • 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 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 names:
    • 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 names:
    • 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 names:
    • Herceptin

Recruiting Locations

Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
MacroGenics

Study Contact

Amy Worth
240-660-0757
wortha@macrogenics.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.