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OpenTrials
Completed

NCT Number: NCT04082364

Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ 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 conducted in two parts.

Part A is a single-arm cohort (Cohort A, 40 to 110 participants) will evaluate safety and efficacy of margetuximab plus retifanlimab.

Part B Part 1 has 4 arms (50 patients/arm). Participants will be randomized to margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab, plus chemotherapy, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy.

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Key information

Conditions

Gastric Cancer Digestive System Diseases Digestive System Neoplasms Gastroesophageal Junction Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms HER2-positive Gastric Cancer Neoplasms Neoplasms by Site Stomach Diseases Stomach Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Beijing Cancer Hospital, Beijing, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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 participants must have had a disease-free interval of at least 6 months from end of chemo/surgery
  • Participants 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

Key Exclusion Criteria:

  • Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions
  • Participants 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

Treatment and study plan

margetuximab

Biological

margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle

Other names: MGAH22, Margenza®

Retifanlimab

Biological

Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.

Other names: MGA012, INCMGA00012

Tebotelimab

Biological

Tebotelimab: anti PD-1, anti-LAG3 bispecific DART (R) molecule 600 mg IV, Day 1 of each 3-week cycle.

Other names: MGD013

trastuzumab

Biological

Anti-HER2 monoclonal antibody 8 mg/kg loading dose and then 6 mg/kg administered IV on Day 1 of each 3-week cycle

Other names: Herceptin

chemotherapy

Other

Investigator choice of 1 of 2 chemotherapy regimens: XELOX or mFOLFOX6

Chemotherapy

XELOX chemotherapy Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion

mFOLFOX6 chemotherapy: Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion.

Primary outcomes

  1. Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0

    Time frame: Throughout the study, an average of 11 months.

    Evaluation of adverse events and serious adverse events (Cohort A)

  2. Objective Response Rate (ORR) for Non-microsatellite Instability-high (Non-MSI-H) Participants (Cohort A) Using Investigator-assessed Radiology Reviews

    Time frame: Throughout the study, an average of 11 months.

    Percent of non MSI-H participants with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A ) based on investigator assessment.

    CR is defined as the disappearance of all target and non-target lesions with no new lesions appearing PR is defined as >= to a 30% decrease in the sum of the longest dimensions of target lesions, non-progression of non- target lesions, with no new lesions appearing.

    CR + PR = ORR

Secondary outcomes

  1. Median Progression-free Survival Using Investigator-assessed Radiology Reviews in Cohort A

    Time frame: Throughout the study, an average of 11 months.

    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) based on investigator assessment

  2. Median Duration of Response in Cohort A Using Investigator-assessed Radiology Reviews

    Time frame: Throughout the study, an average of 11 months.

    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)

  3. Disease Control Rate

    Time frame: Throughout the study, an average of 11 months.

    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)

  4. ORR for Cohort B

    Time frame: Throughout the study, an average of 11 months.

    Proportion of participants with best overall response of CR plus PR per RECIST 1.1

  5. Number of Participants Who Have Antidrug Antibodies (ADA) to Margetuximab

    Time frame: Throughout the study, an average of 11 months.

  6. Number of Participants Who Have ADA to Retifanlimab

    Time frame: Throughout the study, an average of 11 months.

  7. Number of Participants Who Have ADA to Tebotelimab

    Time frame: Throughout the study, an average of 11 months.

Sponsors and collaborators

Lead sponsor

MacroGenics

Industry

Collaborators

  • Zai Lab (Shanghai) Co., Ltd.

Registry information

Official study title

A 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

Acronym: MAHOGANY

Important dates

Study start
2019
Primary completion
2024
Study completion
2025
First posted
Sep 9, 2019
Registry last updated
Jun 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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