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

  • Interventional
  • Not Recruiting
  • NCT04082364
Eligibility Details Visit Clinicaltrials.gov

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

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).

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.

Gender
All

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

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

At a Glance

National Government IDNCT04082364

IRB#IRB19-1078

Lead SponsorMacroGenics

Lead PhysicianDaniel Catenacci

Collaborator(s)N/A

EligibilityAll
18 Years and up
Not Recruiting