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

  • Interventional
  • 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 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.

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. 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

At a Glance

National Government IDNCT04082364

IRB#IRB19-1078

Lead SponsorMacroGenics

Lead PhysicianDaniel Catenacci

Collaborator(s)N/A

EligibilityAll
18 Years and up
Recruiting