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

NCT04082364 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CP-MGAH22-06
• Study Type: interventional
• Target: 82
• Locations: 9 countries
• Sites: 73

Brief Summary

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.

Conditions

Gastric Cancer; Gastroesophageal Junction Cancer; HER2-positive Gastric Cancer

Outcome Measures

Primary Outcomes (2)

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

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

  Throughout the study, an average of 11 months.

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

  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

  Throughout the study, an average of 11 months.

Secondary Outcomes (7)

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

  Throughout the study, an average of 11 months.

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

  Throughout the study, an average of 11 months.

• Disease Control Rate

  Throughout the study, an average of 11 months.

• ORR for Cohort B

  Throughout the study, an average of 11 months.

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

  Throughout the study, an average of 11 months.

Study Arms (5)

Chemotherapy-free arm

EXPERIMENTAL

margetuximab plus retifanlimab

Biological: margetuximab; Biological: Retifanlimab

Margetuximab, retifanlimab, and chemotherapy arm

EXPERIMENTAL

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; Biological: Retifanlimab; Other: Chemotherapy

Margetuximab, tebotelimab and chemotherapy arm

EXPERIMENTAL

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; Biological: Tebotelimab; Other: Chemotherapy

Margetuximab and chemotherapy arm

EXPERIMENTAL

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; Other: Chemotherapy

Trastuzumab and chemotherapy arm

ACTIVE COMPARATOR

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

Biological: Trastuzumab; Other: Chemotherapy

Interventions

margetuximab BIOLOGICAL

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

Also known as: MGAH22, Margenza®

Chemotherapy-free arm; Margetuximab and chemotherapy arm; Margetuximab, retifanlimab, and chemotherapy arm; Margetuximab, tebotelimab and chemotherapy arm

Retifanlimab BIOLOGICAL

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

Also known as: MGA012, INCMGA00012

Chemotherapy-free arm; Margetuximab, retifanlimab, and chemotherapy arm

Tebotelimab BIOLOGICAL

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

Also known as: MGD013

Margetuximab, tebotelimab and chemotherapy arm

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

Also known as: Herceptin

Trastuzumab and chemotherapy arm

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.

Margetuximab and chemotherapy arm; Margetuximab, retifanlimab, and chemotherapy arm; Margetuximab, tebotelimab and chemotherapy arm; Trastuzumab and chemotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MacroGenics: lead
• Zai Lab (Shanghai) Co., Ltd.: collaborator

Study Sites (73)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, 91010, United States

Location

Norris Comprehensive Cancer Center (USC)

Los Angeles, California, 90033, United States

Location

Salinas Memorial

Salinas, California, 93901, United States

Location

UCLA School of Medicine

Santa Monica, California, 90404, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Florida Cancer Specialists South

Fort Myers, Florida, 33901, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala

Ocala, Florida, 34474, United States

Location

Florida Cancer Specialists North

St. Petersburg, Florida, 33705, United States

Location

Kaiser Permanente

Honolulu, Hawaii, 96814, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Edward H. Kaplan MD & Associates

Skokie, Illinois, 60076, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Heme Onc

Lincoln, Nebraska, 68506, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

The University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Stephenson Cancer Center at OUHSC

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Oncology Consultants

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)

Changchun, 130000, China

Location

Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)

Fuzhou, 350005, China

Location

SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine

Hangzhou, 310016, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin

Harbin, 150081, China

Location

The First Affiliated Hospital of Anhui Medical University

Hefei, 230022, China

Location

Anhui Provincial Cancer Hospital

Hefei, 230031, China

Location

Jinan Center Hospital

Jinan, 250013, China

Location

Nanjing University Medical School; Nanjing Drug Tower

Nanjing, 210000, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200433, China

Location

Liaoning cancer hospital

Shenyang, 110042, China

Location

Hebei cancer hospital (The Fourth Affiliate)

Shijiazhuang, 050000, China

Location

Wuhan Union Hospital

Wuhan, 430022, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhenzhou, 450052, China

Location

Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)

Frankfurt, 60488, Germany

Location

Haematologisch-Onkologische Praxis Eppendorf

Hamburg, Germany

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Kliniken Maria Hilf GmbH

Mönchengladbach, Germany

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Istituto Europeo Di Oncologia

Milan, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56126, Italy

Location

SPSK nr 1 in Lublin

Lublin, 20-081, Poland

Location

Centrum Medyczne MrukMed

Rzeszów, 35-922, Poland

Location

National University Hospital (Cancer Institute) -Singapore

Singapore, 119074, Singapore

Location

National Cancer Center Singapore

Singapore, 169610, Singapore

Location

Hallym University Sacred Heart Hospital

Anyang-si, 14068, South Korea

Location

CHA bundang

Gyeonggi-do, South Korea

Location

Inje University Haeundae Paik Hospital

Haeundae, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Korea University Guro

Seoul, South Korea

Location

Korea University, Anam Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Yonsei University College of Medicine (Severance Hospital)

Seoul, South Korea

Location

Catholic University of Korea St. Vincent Hospital

Suwon, South Korea

Location

Taipei Medical University Hospital

Taipei City, Taipei, 110, Taiwan

Location

Kaohsiung Chang Gung MemorialHospital

Kaohsiung City, 83301, Taiwan

Location

Chang Gung Memorial Hospital, Keelung

Keelung, 204, Taiwan

Location

Liuying Chi MeiMedical Hospital

Tainan, 73657, Taiwan

Location

National Taiwan University

Taipei, Taiwan

Location

Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital

Cambridge, United Kingdom

Location

The Christie Hospital NHS Foundation Trust

Manchester, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33263418 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

margetuximab; Trastuzumab; Drug Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Chief Medical Officer
• Organization: MacroGenics, Inc.

info@macrogenics.com

301-251-5172

Study Officials

• Stephen L. Eck, MD, PhD

  MacroGenics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort A is a single-arm cohort to evaluate safety and efficacy of margetuximab plus retifanlimab. Cohort B Part 1 is a randomized, 4-arm segment to evaluate margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab plus chemotherapy, margetuximab plus chemotherapy, vs trastuzumab plus chemotherapy.

Study Record Dates

• First Submitted: September 5, 2019
• First Posted: September 9, 2019
• Study Start: September 30, 2019
• Primary Completion: January 15, 2024
• Study Completion: March 25, 2025
• Last Updated: June 8, 2025
• Results First Posted: April 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (28); KR (11); GB (2); DE (4); TW (5); IT (3); CN (16); SG (2); PL (2)