Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer
NCT ID: NCT04082364
Last Updated: 2025-06-08
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2/PHASE3
82 participants
INTERVENTIONAL
2019-09-30
2025-03-25
Brief Summary
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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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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Chemotherapy-free arm
margetuximab plus retifanlimab
margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Retifanlimab
Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.
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)
margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Retifanlimab
Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.
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.
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)
margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Tebotelimab
Tebotelimab: anti PD-1, anti-LAG3 bispecific DART (R) molecule 600 mg IV, Day 1 of each 3-week cycle.
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.
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)
margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
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.
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)
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
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.
Interventions
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margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
Retifanlimab
Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.
Tebotelimab
Tebotelimab: anti PD-1, anti-LAG3 bispecific DART (R) molecule 600 mg IV, Day 1 of each 3-week cycle.
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
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. 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
2. Participants 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
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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Zai Lab (Shanghai) Co., Ltd.
INDUSTRY
MacroGenics
INDUSTRY
Responsible Party
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Principal Investigators
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Stephen L. Eck, MD, PhD
Role: STUDY_DIRECTOR
MacroGenics
Locations
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Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center - Duarte
Duarte, California, United States
Norris Comprehensive Cancer Center (USC)
Los Angeles, California, United States
Salinas Memorial
Salinas, California, United States
UCLA School of Medicine
Santa Monica, California, United States
Yale University
New Haven, Connecticut, United States
Florida Cancer Specialists South
Fort Myers, Florida, United States
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States
Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
Ocala, Florida, United States
Florida Cancer Specialists North
St. Petersburg, Florida, United States
Kaiser Permanente
Honolulu, Hawaii, United States
University of Chicago
Chicago, Illinois, United States
Edward H. Kaplan MD & Associates
Skokie, Illinois, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Henry Ford Health System
Detroit, Michigan, United States
Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
Grand Rapids, Michigan, United States
Mayo Clinic - Rochester
Rochester, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Nebraska Heme Onc
Lincoln, Nebraska, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
The University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, United States
Stephenson Cancer Center at OUHSC
Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Oncology Consultants
Houston, Texas, United States
Utah Cancer Specialists
Salt Lake City, Utah, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Swedish Cancer Institute
Seattle, Washington, United States
University of Wisconsin
Madison, Wisconsin, United States
Beijing Cancer Hospital
Beijing, , China
Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)
Changchun, , China
Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
Fuzhou, , China
SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine
Hangzhou, , China
Zhejiang Cancer Hospital
Hangzhou, , China
Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
Harbin, , China
The First Affiliated Hospital of Anhui Medical University
Hefei, , China
Anhui Provincial Cancer Hospital
Hefei, , China
Jinan Center Hospital
Jinan, , China
Nanjing University Medical School; Nanjing Drug Tower
Nanjing, , China
Zhongshan Hospital Fudan University
Shanghai, , China
Liaoning cancer hospital
Shenyang, , China
Hebei cancer hospital (The Fourth Affiliate)
Shijiazhuang, , China
Wuhan Union Hospital
Wuhan, , China
Henan Cancer Hospital
Zhengzhou, , China
The First Affiliated Hospital of Zhengzhou University
Zhenzhou, , China
Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)
Frankfurt, , Germany
Haematologisch-Onkologische Praxis Eppendorf
Hamburg, , Germany
Universitätsmedizin Mainz
Mainz, , Germany
Kliniken Maria Hilf GmbH
Mönchengladbach, , Germany
Ospedale San Raffaele
Milan, , Italy
Istituto Europeo Di Oncologia
Milan, , Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa, , Italy
SPSK nr 1 in Lublin
Lublin, , Poland
Centrum Medyczne MrukMed
Rzeszów, , Poland
National University Hospital (Cancer Institute) -Singapore
Singapore, , Singapore
National Cancer Center Singapore
Singapore, , Singapore
Hallym University Sacred Heart Hospital
Anyang-si, , South Korea
CHA bundang
Gyeonggi-do, , South Korea
Inje University Haeundae Paik Hospital
Haeundae, , South Korea
Seoul National University Bundang Hospital
Seongnam-si, , South Korea
Asan Medical Center
Seoul, , South Korea
Korea University Guro
Seoul, , South Korea
Korea University, Anam Hospital
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Yonsei University College of Medicine (Severance Hospital)
Seoul, , South Korea
Catholic University of Korea St. Vincent Hospital
Suwon, , South Korea
Taipei Medical University Hospital
Taipei City, Taipei, Taiwan
Kaohsiung Chang Gung MemorialHospital
Kaohsiung City, , Taiwan
Chang Gung Memorial Hospital, Keelung
Keelung, , Taiwan
Liuying Chi MeiMedical Hospital
Tainan City, , Taiwan
National Taiwan University
Taipei, , Taiwan
Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital
Cambridge, , United Kingdom
The Christie Hospital NHS Foundation Trust
Manchester, , United Kingdom
Countries
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References
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Catenacci DV, Rosales M, Chung HC, H Yoon H, Shen L, Moehler M, Kang YK. MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Future Oncol. 2021 Apr;17(10):1155-1164. doi: 10.2217/fon-2020-1007. Epub 2020 Dec 2.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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CP-MGAH22-06
Identifier Type: -
Identifier Source: org_study_id
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