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

December 22, 2023 updated by: MacroGenics

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

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 patients) will evaluate safety and efficacy of margetuximab plus retifanlimab.

Part B has 2 subparts. Cohort B1 has 4 arms (50 patients/arm). Patients will be randomized to margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab, plus chemotherapy, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy. The most effective combination with margetuximab from Cohort B1 will be used in Cohort B2.

Cohort B2 has 2 arms (250 patients/arm). Patients will be randomized to margetuximab plus retifanlimab or tebotelimab plus chemotherapy, or to trastuzumab plus chemotherapy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100142
        • Beijing Cancer Hospital
      • Changchun, China, 130000
        • Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)
      • Fuzhou, China, 350005
        • Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
      • Hangzhou, China, 310016
        • Sir Run Run Shaw Hospital, Zhejiang University School Of Medicine
      • Hangzhou, China, 310022
        • Zhejiang Cancer Hospital
      • Harbin, China, 150081
        • Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
      • Hefei, China, 230022
        • The First affiliated Hospital of Anhui Medical University
      • Hefei, China, 230031
        • Anhui Provincial Cancer Hospital
      • Jinan, China, 250013
        • Jinan Center Hospital
      • Nanjing, China, 210000
        • Nanjing University Medical School; Nanjing Drug Tower
      • Shanghai, China, 200433
        • Zhongshan Hospital Fudan University
      • Shenyang, China, 110042
        • Liaoning cancer hospital
      • Shijiazhuang, China, 050000
        • Hebei cancer hospital (The Fourth Affiliate)
      • Wuhan, China, 430022
        • Wuhan Union Hospital
      • Zhengzhou, China, 450008
        • Henan Cancer Hospital
      • Zhenzhou, China, 450052
        • The First Affiliated Hospital of Zhengzhou University
  • Germany
      • Frankfurt, Germany, 60488
        • Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)
      • Hamburg, Germany
        • Haematologisch-Onkologische Praxis Eppendorf
      • Mainz, Germany
        • Universitätsmedizin Mainz
      • Monchengladbach, Germany
        • Kliniken Maria Hilf GmbH
  • Italy
      • Milan, Italy, 20132
        • Ospedale San Raffaele
      • Milan, Italy
        • Istituto Europeo di Oncologia
      • Pisa, Italy, 56126
        • Azienda Ospedaliero-Universitaria Pisana
  • Korea, Republic of
      • Anyang-Si, Korea, Republic of, 14068
        • Hallym University Sacred Heart Hospital
      • Gyeonggi-do, Korea, Republic of
        • CHA bundang
      • Haeundae, Korea, Republic of
        • Inje University Haeundae Paik Hospital
      • Seongnam-si, Korea, Republic of
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Korea University Guro
      • Seoul, Korea, Republic of
        • Korea University, Anam Hospital
      • Seoul, Korea, Republic of
        • Yonsei University College of Medicine (Severance Hospital)
      • Suwon, Korea, Republic of
        • Catholic University of Korea St. Vincent Hospital
  • Poland
      • Lublin, Poland, 20-081
        • SPSK nr 1 in Lublin
      • Rzeszów, Poland, 35-922
        • Centrum Medyczne MrukMed
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Center Singapore
      • Singapore, Singapore, 119074
        • National University Hospital (Cancer Institute) -Singapore
  • Taiwan
      • Kaohsiung, Taiwan, 83301
        • Kaohsiung Chang Gung MemorialHospital
      • Keelung, Taiwan, 204
        • Chang Gung Memorial Hospital, Keelung
      • Tainan city, Taiwan, 73657
        • Liuying Chi MeiMedical Hospital
      • Taipei, Taiwan
        • National Taiwan University
    • Taipei
      • Taipei City, Taipei, Taiwan, 110
        • Taipei Medical University Hospital
  • United Kingdom
      • Cambridge, United Kingdom
        • Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital
      • Manchester, United Kingdom
        • The Christie Hospital NHS Foundation Trust
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic - Scottsdale
    • California
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center - Duarte
      • Los Angeles, California, United States, 90033
        • Norris Comprehensive Cancer Center (USC)
      • Salinas, California, United States, 93901
        • Salinas Memorial
      • Santa Monica, California, United States, 90404
        • UCLA School of Medicine
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale University
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists South
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Jacksonville
      • Ocala, Florida, United States, 34474
        • Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists NORTH
    • Hawaii
      • Honolulu, Hawaii, United States, 96814
        • Kaiser Permanente
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University Of Chicago
      • Skokie, Illinois, United States, 60076
        • Edward H. Kaplan MD & Associates
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Grand Rapids, Michigan, United States, 49503
        • Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Nebraska Heme Onc
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • The University of New Mexico Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center at OUHSC
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Oncology Consultants
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemotherapy-free arm
margetuximab plus retifanlimab
Biological: margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Other Names:
  • MGAH22
  • Margenza®
Biological: Retifanlimab
Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.
Other Names:
  • INCMGA00012
  • MGA012
Experimental: Margetuximab, retifanlimab, and chemotherapy arm

margetuximab plus retifanlimab plus investigator choice of chemotherapy options.

Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
Biological: margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Other Names:
  • MGAH22
  • Margenza®
Biological: Retifanlimab
Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.
Other Names:
  • INCMGA00012
  • MGA012
Other: Chemotherapy

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.
Experimental: Margetuximab, tebotelimab and chemotherapy arm
margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
Biological: margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Other Names:
  • MGAH22
  • Margenza®
Other: Chemotherapy

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.

Biological: Tebotelimab
Tebotelimab: anti PD-1, anti-LAG3 bispecific DART (R) molecule 600 mg IV, Day 1 of each 3-week cycle.
Other Names:
  • MGD013
Experimental: Margetuximab and chemotherapy arm
margetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
Biological: margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Other Names:
  • MGAH22
  • Margenza®
Other: Chemotherapy

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.
Active Comparator: Trastuzumab and chemotherapy arm
Trastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
Other: Chemotherapy

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.

Biological: Trastuzumab
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events of margetuximab plus retifanlimab as assessed by CTCAE v5.0
Time Frame: Throughout the study up to 24 months
Evaluation of adverse events and serious adverse events (Cohort A)
Throughout the study up to 24 months
Objective response rate (ORR) for non-microsatellite instability-high (non-MSI-H) patients (Cohort A)
Time Frame: Throughout the study up to 24 months
Proportion of non MSI-H patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A )
Throughout the study up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: Up to 3 years
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)
Up to 3 years
Duration of response
Time Frame: Up to 3 years
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)
Up to 3 years
Disease control rate
Time Frame: Up to 3 years
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)
Up to 3 years
ORR for Cohort B
Time Frame: Throughout study participation, up to 24 months.
Proportion of non-MSI-high patients iwth best overall response of CR plus PR per RECIST 1.1
Throughout study participation, up to 24 months.
Number of patients who have antidrug antibodies (ADA) to margetuximab
Time Frame: Throughout study participation, up to 24 months.
Throughout study participation, up to 24 months.
Number of patients who have ADA to retifanlimab
Time Frame: Throughout study participation, up to 24 months.
Throughout study participation, up to 24 months.
Number of patients who have ADA to tebotelimab
Time Frame: Throughout study participation, up to 24 months.
Throughout study participation, up to 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MacroGenics

Collaborators

Zai Lab (Shanghai) Co., Ltd.

Investigators

  • Study Director: Stephen L. Eck, MD, PhD, MacroGenics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2019

Primary Completion (Estimated)

March 1, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

September 5, 2019

First Submitted That Met QC Criteria

September 5, 2019

First Posted (Actual)

September 9, 2019

Study Record Updates

Last Update Posted (Actual)

December 26, 2023

Last Update Submitted That Met QC Criteria

December 22, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP-MGAH22-06

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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