Clinical Trials /

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

NCT04082364

Description:

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).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CP-MGAH22-06
  • NCT ID: NCT04082364

Conditions

  • Gastric Cancer
  • Gastroesophageal Junction Cancer
  • HER2-positive Gastric Cancer

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).

Detailed Description

      A single-arm cohort (Cohort A, 40 to 100 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 Arms

NameTypeDescriptionInterventions
Margetuximab plus INCMGA00012Experimentalmargetuximab plus INCMGA00012
    Margetuximab plus INCMGA00012 plus chemoExperimentalmargetuximab plus INCMGA00012 plus capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
      Margetuximab plus MGD013 plus chemoExperimentalmargetuximab plus MGD013 plus XELOX or mFOLFOX-6
        Margetuximab plus chemoExperimentalmargetuximab plus XELOX or mFOLFOX-6
          Control ArmActive ComparatorTrastuzumab plus XELOX or mFOLFOX-6

            Eligibility Criteria

                    Key Inclusion Criteria:
            
                      -  Histologically confirmed diagnosis of previously untreated locally advanced
                         unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
            
                           1. Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥
                              1%), and non-MSI-H per central review
            
                              1%), and non-MSI-H per central review
            
                           2. 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 MSI-H status by central test in Cohort A, or patients with known
                              MSI-H status in Cohort B
            
                      -  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
                  
            Maximum Eligible Age:N/A
            Minimum Eligible Age:18 Years
            Eligible Gender:All
            Healthy Volunteers:No

            Primary Outcome Measures

            Measure:Incidence of Adverse Events of margetuximab plus INCMGA00012 as assessed by CTCAE v5.0
            Time Frame:6 month intervals
            Safety Issue:
            Description:Evaluation of adverse events and serious adverse events (Cohort A)

            Secondary Outcome Measures

            Measure:Progression-free survival
            Time Frame:Up to 3 years
            Safety Issue:
            Description: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)
            Measure:Duration of response
            Time Frame:Up to 3 years
            Safety Issue:
            Description: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)
            Measure:Disease control rate
            Time Frame:Up to 3 years
            Safety Issue:
            Description: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)
            Measure:Patient reported quality of life
            Time Frame:Up to 3 years
            Safety Issue:
            Description:Quality of life as assessed using the Functional Assessment of Cancer Therapy - Gastric Questionnaire (FACT-Ga) (Cohort B)

            Details

            Phase:Phase 2/Phase 3
            Primary Purpose:Interventional
            Overall Status:Not yet recruiting
            Lead Sponsor:MacroGenics

            Trial Keywords

            • gastric cancer
            • gastroesophageal junction cancer
            • HER2-positive gastroesophageal cancer
            • anti-HER2 therapy
            • checkpoint inhibitors
            • PD-1
            • LAG-3

            Last Updated