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

Trial Status: Active

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).

Inclusion Criteria

  • Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
  • 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
  • Patients receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility
  • Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%) per central review
  • 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

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE

Florida

Jacksonville
Mayo Clinic in Florida
Status: ACTIVE

Minnesota

Rochester
Mayo Clinic in Rochester
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New Jersey

New Brunswick
Rutgers Cancer Institute of New Jersey
Status: IN_REVIEW

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: ACTIVE

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: APPROVED

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.

Trial Phase Phase II/III

Trial Type Treatment

Lead Organization
MacroGenics Inc

  • Primary ID CP-MGAH22-06
  • Secondary IDs NCI-2019-07167
  • Clinicaltrials.gov ID NCT04082364