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Gastric CancerPhase 2/3MAHOGANYNCT04082364

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

A Phase 2/3 study testing margetuximab, Retifanlimab and Tebotelimab in people with Gastric Cancer and Gastroesophageal Junction Cancer, run by MacroGenics at 73 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
margetuximab, Retifanlimab and Tebotelimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
73 sitesin 9 countries
Study dates
30 Sep 2019to 25 Mar 2025
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

73 sites in 9 countries.

73 sites in 9 countries

United States28 sites

  • The University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87131

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • University of Chicago

    Chicago, Illinois, 60637

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • City of Hope Comprehensive Cancer Center - Duarte

    Duarte, California, 91010

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Florida Cancer Specialists South

    Fort Myers, Florida, 33901

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

    Grand Rapids, Michigan, 49503

  • Kaiser Permanente

    Honolulu, Hawaii, 96814

  • Oncology Consultants

    Houston, Texas, 77030

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Nebraska Heme Onc

    Lincoln, Nebraska, 68506

  • Norris Comprehensive Cancer Center (USC)

    Los Angeles, California, 90033

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06511

  • Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala

    Ocala, Florida, 34474

  • Stephenson Cancer Center at OUHSC

    Oklahoma City, Oklahoma, 73104

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • Salinas Memorial

    Salinas, California, 93901

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • UCLA School of Medicine

    Santa Monica, California, 90404

  • Mayo Clinic - Scottsdale

    Scottsdale, Arizona, 85259

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Edward H. Kaplan MD & Associates

    Skokie, Illinois, 60076

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Florida Cancer Specialists North

    St. Petersburg, Florida, 33705

Other trials in United States

China16 sites

  • Beijing Cancer Hospital

    Beijing, 100142

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

    Changchun, 130000

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

    Fuzhou, 350005

  • SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine

    Hangzhou, 310016

  • Zhejiang Cancer Hospital

    Hangzhou, 310022

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

    Harbin, 150081

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, 230022

  • Anhui Provincial Cancer Hospital

    Hefei, 230031

  • Jinan Center Hospital

    Jinan, 250013

  • Nanjing University Medical School; Nanjing Drug Tower

    Nanjing, 210000

  • Zhongshan Hospital Fudan University

    Shanghai, 200433

  • Liaoning cancer hospital

    Shenyang, 110042

  • Hebei cancer hospital (The Fourth Affiliate)

    Shijiazhuang, 050000

  • Wuhan Union Hospital

    Wuhan, 430022

  • Henan Cancer Hospital

    Zhengzhou, 450008

  • The First Affiliated Hospital of Zhengzhou University

    Zhenzhou, 450052

Other trials in China

South Korea11 sites

  • Hallym University Sacred Heart Hospital

    Anyang-si, 14068

  • CHA bundang

    Gyeonggi-do

  • Inje University Haeundae Paik Hospital

    Haeundae

  • Seoul National University Bundang Hospital

    Seongnam-si

  • Asan Medical Center

    Seoul

  • Korea University Guro

    Seoul

  • Korea University, Anam Hospital

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Yonsei University College of Medicine (Severance Hospital)

    Seoul

  • Catholic University of Korea St. Vincent Hospital

    Suwon

Other trials in South Korea

Taiwan5 sites

  • Kaohsiung Chang Gung MemorialHospital

    Kaohsiung City, 83301

  • Chang Gung Memorial Hospital, Keelung

    Keelung, 204

  • Liuying Chi MeiMedical Hospital

    Tainan, 73657

  • National Taiwan University

    Taipei

  • Taipei Medical University Hospital

    Taipei City, Taipei, 110

Other trials in Taiwan

Germany4 sites

  • Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)

    Frankfurt, 60488

  • Haematologisch-Onkologische Praxis Eppendorf

    Hamburg

  • Universitätsmedizin Mainz

    Mainz

  • Kliniken Maria Hilf GmbH

    Mönchengladbach

Other trials in Germany

Italy3 sites

  • Ospedale San Raffaele

    Milan, 20132

  • Istituto Europeo Di Oncologia

    Milan

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa, 56126

Other trials in Italy

Poland2 sites

  • SPSK nr 1 in Lublin

    Lublin, 20-081

  • Centrum Medyczne MrukMed

    Rzeszów, 35-922

Other trials in Poland

Singapore2 sites

  • National University Hospital (Cancer Institute) -Singapore

    Singapore, 119074

  • National Cancer Center Singapore

    Singapore, 169610

Other trials in Singapore

United Kingdom2 sites

  • Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital

    Cambridge

  • The Christie Hospital NHS Foundation Trust

    Manchester

Other trials in United Kingdom

About this study

Official 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

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.

Being tested
margetuximab, Retifanlimab, Tebotelimab, Trastuzumab, Chemotherapy
Medical subject headings
Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • margetuximabBiological

    Also called MGAH22, Margenza®

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

  • RetifanlimabBiological

    Also called MGA012, INCMGA00012

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

  • TebotelimabBiological

    Also called MGD013

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

  • TrastuzumabBiological

    Also called Herceptin

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

  • ChemotherapyOther

    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.

Study groups in NCT04082364
Study groupRoleWhat they receive
Chemotherapy-free armExperimentalmargetuximab plus retifanlimab
Receives: Biological: margetuximab; Biological: Retifanlimab
Margetuximab, retifanlimab, and chemotherapy armExperimentalmargetuximab 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)
Receives: Biological: margetuximab; Biological: Retifanlimab; Other: Chemotherapy
Margetuximab, tebotelimab and chemotherapy armExperimentalmargetuximab 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)
Receives: Biological: margetuximab; Biological: Tebotelimab; Other: Chemotherapy
Margetuximab and chemotherapy armExperimentalmargetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
Receives: Biological: margetuximab; Other: Chemotherapy
Trastuzumab and chemotherapy armActive comparatorTrastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
Receives: Biological: Trastuzumab; Other: Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Throughout the study, an average of 11 months.

  2. 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

    Measured: Throughout the study, an average of 11 months.

Secondary outcomes (7)

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

    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

    Measured: Throughout the study, an average of 11 months.

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

    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)

    Measured: Throughout the study, an average of 11 months.

  3. Disease Control Rate

    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)

    Measured: Throughout the study, an average of 11 months.

  4. ORR for Cohort B

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

    Measured: Throughout the study, an average of 11 months.

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

    Measured: Throughout the study, an average of 11 months.

  6. Number of Participants Who Have ADA to Retifanlimab

    Measured: Throughout the study, an average of 11 months.

  7. Number of Participants Who Have ADA to Tebotelimab

    Measured: Throughout the study, an average of 11 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2019
  2. Study start30 Sep 2019
  3. Primary completion15 Jan 2024
  4. Study completion25 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04082364
Sponsor's protocol ID
CP-MGAH22-06
Acronym
MAHOGANY
Status last verified
May 2025
First submitted
5 Sep 2019
Last updated
8 Jun 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bautista J, Echeverria CE, Maldonado-Noboa I, Adatty-Molina J, Suarez Urresta S, Coral-Riofrio EC, Araujo-Abad S, Kyriakidis NC, Lopez-Cortes A. Next-Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy. J Immunol Res. 2026;2026(1):e7864229. doi: 10.1155/jimr/7864229.

    PubMed 41811823

  • 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.

    PubMed 33263418

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing margetuximab, Retifanlimab and Tebotelimab in people with Gastric Cancer and Gastroesophageal Junction Cancer, run by MacroGenics at 73 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United States, China, South Korea, Taiwan, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04082364, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2025.

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