MAHOGANY
Research type
Research Study
Full 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
IRAS ID
282019
Contact name
Muzamil Asif
Contact email
Sponsor organisation
MacroGenics, Inc.
Eudract number
2019-004699-21
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 7 months, 30 days
Research summary
Summary of Research
This is a Phase 2/3, randomised, open-label study for the treatment of patients with HER2-positive Gastric cancer (GC) or Gastroesophageal Junction (GEJ) cancer to determine the efficacy of margetuximab combined with INCMGA00012 (also known as MGA012) (Cohort A) and margetuximab combined with INCMGA00012 or MGD013 and chemotherapy compared to trastuzumab combined with chemotherapy (Cohort B).
A single-arm cohort (Cohort A, 40 to 110 patients) will evaluate safety and efficacy of margetuximab plus INCMGA00012.
In a 4-arm cohort (Cohort B Part 1, 50 patients per arm), patients will be randomized to margetuximab plus chemotherapy plus INCMGA00012, margetuximab plus chemotherapy plus MGD013, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy. A checkpoint inhibitor (CPI) (INCMGA00012 or MGD013) will be selected from Cohort B Part 1 and evaluated in a randomized 2-arm cohort (Cohort B Part 2, 250 patients per arm) of margetuximab plus chemotherapy plus INCMGA00012 or MGD013, or trastuzumab plus chemotherapy.
Summary of Results
Thank You to Study Participants We sincerely thank all the individuals who participated in this study. Your involvement has been essential in advancing research for HER2-positive gastric and gastroesophageal cancers.
General Information About the Research
• 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.
• Who Carried Out the Research: The study was sponsored and funded by MacroGenics, Inc., a biopharmaceutical company. The coordinating principal investigator was Dr. Daniel Catenacci, formerly of the University of Chicago.
• Public Involvement: The report does not mention direct public or patient involvement in the design or conduct of the study.
• Where and When the Study Took Place: The study was conducted at 70 sites across 9 countries, including the U.S., China, South Korea, and others, between October 15, 2019, and May 28, 2024.
• Why Was the Research Needed: HER2-positive gastric and gastroesophageal cancers are aggressive and difficult to treat. This study aimed to explore whether combining new immunotherapies with standard treatments could improve outcomes.
• Main Questions Studied:
1. Is the combination of margetuximab and retifanlimab safe and effective?
2. How does this combination compare to standard treatments like trastuzumab plus chemotherapy?Who Participated in the Study?
• Cohort A: 48 participants with HER2-positive and PD-L1-positive cancers.
• Cohort B Part 1: 34 participants with HER2-positive cancers regardless of PD-L1 status.
• Most participants were male, aged around 63 years, and either White or Asian.
What Treatments Did Participants Receive?
• Cohort A: Received margetuximab and retifanlimab every 3 weeks.
• Cohort B: Participants were randomized into four groups:
- Trastuzumab + chemotherapy (control)
- Margetuximab + retifanlimab + chemotherapy
- Margetuximab + tebotelimab + chemotherapy
- Margetuximab + chemotherapyWhat Medical Problems (Side Effects) Did Participants Have?
“Side effects” are defined as unwanted medical events that the study doctors thought might be caused by the study treatment.• In Cohort A, most participants (79%) experienced at least one side effect. Common ones included diarrhea, nausea, vomiting, anemia, and fatigue.
• Serious side effects occurred in 42% of participants, and 2% had fatal side effects.• In Cohort B, nearly all participants (94%) experienced at least one side effect. Common side effects included low blood counts, liver enzyme changes, and gastrointestinal issues.
• Serious side effects occurred in 18% of participants, and no participants had fatal side effects.What Happened During the Study?
• Participants were treated in cycles and monitored for tumor response and side effects.
• The study was stopped early for business reasons, not due to safety concerns.What Were the Results of the Study?
• Cohort A: The combination of margetuximab and retifanlimab showed a 52.1% response rate, with a median response duration of 16.1 months.
• Cohort B: All treatment arms showed tumor responses, with the highest response rate (90%) in the group receiving margetuximab + chemotherapy.How Has This Study Helped Patients and Researchers?
This study supports the potential of combining margetuximab with immunotherapies and chemotherapy to treat HER2-positive gastric cancers. It provides valuable safety and efficacy data that can guide future treatment strategies.Details of Any Further Research Planned
The study was closed early. No further development is planned by the sponsor. However, the findings may inform future trials.Where Can I Learn More About This Study?
You can find more details on the clinical trial registry at https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%2FNBTI%2FvGG_AQ%2FAQ%2F9892b14d-a67f-4852-9d1b-2a87744b8436%2F2%2FzIEaUygpqo&data=05%7C02%7Capprovals%40hra.nhs.uk%7C4f5976f93e2545bc7ae808ddb874b046%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638869533501001246%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=s65%2F%2BGf9zlBOgg8oj3o4H4rC82XCJL44mWqODHMPhFI%3D&reserved=0 using the identifier NCT04082364.REC name
East of Scotland Research Ethics Service REC 2
REC reference
20/ES/0072
Date of REC Opinion
3 Sep 2020
REC opinion
Further Information Favourable Opinion