Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
A Phase 1b/2, Open Label, Dose Escalation Study of Margetuximab in Combination With Pembrolizumab in Patients With Relapsed/Refractory Advanced HER2+ Gastroesophageal Junction or Gastric Cancer
1 other identifier
interventional
95
5 countries
28
Brief Summary
This main purpose of this clinical study is to learn about the safety and activity of margetuximab and pembrolizumab combination treatment in patients with HER2+ gastric and gastroesophageal junction cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 gastric-cancer
Started Jan 2016
Typical duration for phase_1 gastric-cancer
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2016
CompletedFirst Submitted
Initial submission to the registry
January 27, 2016
CompletedFirst Posted
Study publicly available on registry
February 23, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2021
CompletedResults Posted
Study results publicly available
August 4, 2022
CompletedMarch 17, 2025
February 1, 2025
5 years
January 27, 2016
February 28, 2022
February 24, 2025
Conditions
Outcome Measures
Primary Outcomes (5)
Number of Patients With Dose Limiting Toxicities
Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab when administered in combination with pembrolizumab
21 days
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).
The number of patients that experience either an AE or a SAE during the study participation
up to 24 months
Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment
Investigate the preliminary anti-tumor activity as measured by response to treatment of margetuximab when administered in combination with pembrolizumab, using conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
12 months
Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment Using irRC Criteria
Investigate the preliminary anti-tumor activity, as measured by objective response rate (ORR) of margetuximab when administered in combination with pembrolizumab, using immune-related response criteria (irRC).
12 Months
Duration of Response
Duration of response is calculated at the time from CR or PR to relapse or cancer progression.
up to 24 months
Secondary Outcomes (10)
Overall Survival (OS)
24 Months
Progression Free Survival (PFS)
24 Months
Change From Baseline in Pharmacodynamic Markers in Whole Blood
from first dose to the end of treatment, average about 12 months
Analysis of HER2 Tumor Cell Membrane Expression in Biopsy Specimens Before and After Treatment
from first dose to the end of treatment, average 12 months.
Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab (Immunogenicity)
Assessed Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Day 1 of every odd cycle, and end of treatment visit, average 12 months
- +5 more secondary outcomes
Study Arms (2)
Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg
EXPERIMENTALmargetuximab administered in combination with pembrolizumab
Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg
EXPERIMENTALmargetuximab administered in combination with pembrolizumab
Interventions
Margetuximab treatment is administered intravenously (IV) once every 21-day cycle
Margetuximab treatment is administered IV once every 21-day cycle
Pembrolizumab treatment is administered IV once every 21-day cycle
Eligibility Criteria
You may qualify if:
- Signed written informed consent.
- Age ≥ 18 years old (or minimum age based upon local regulations)
- Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric cancer. Gastric Cancer Expansion Phase will include only gastric cancer patients with 3+ HER2 positivity.
- HER2+ as 3+ (as defined in AJCC staging manual 8th edition) by IHC or in-situ hybridation (ISH) amplified.
- Have received prior treatment with trastuzumab.
- Have received treatment with at least one or more lines of cytotoxic chemotherapy in the metastatic setting.
- Resolution of chemotherapy, immunotherapy or radiation-related toxicities.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 12 weeks.
- Measurable disease as per RECIST 1.1 criteria.
You may not qualify if:
- Patients with symptomatic central nervous system (CNS) metastases.
- Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
- History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
- Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.
- Treatment with radiation therapy within 3 weeks prior to the initiation of study drug administration.
- Treatment with corticosteroids (≥10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
- History of clinically-significant cardiovascular disease.
- Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
- History of (non-infectious) pneumonitis that required steroids or presence of active pneumonitis
- Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
- Evidence of active viral, bacterial, or systemic fungal infection.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MacroGenicslead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (28)
Yale School of Medicine
New Haven, Connecticut, 06520, United States
Georgetown University-Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007, United States
University of Chicago
Chicago, Illinois, 60637, United States
Johns Hopkins University Medical Center
Baltimore, Maryland, 21231, United States
Dana-Farber Cancer Institute/Harvard University Medical Center
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19107, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Swedish Cancer Institute
Seattle, Washington, 98104, United States
Juravinski Cancer Centre - McMaster University
Hamilton, Ontario, L8V5C2, Canada
McGill University Health Centre
Montreal, Quebec, H4A3J1, Canada
National Cancer Centre
Singapore, Singapore
National University Hospital
Singapore, Singapore
Raffles Hospital
Singapore, Singapore
Kyungbuk National University Hospital
Daegu, 41404, South Korea
Gachon University Gil Medical Center
Incheon, 21565, South Korea
Chonbuk National University Hospital
Seoul, 54907, South Korea
Asan Medical Center
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Korea University Guro Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Bundang Hospital
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Tri-Service General Hospital
Taipei, Taiwan
Related Publications (2)
Catenacci DV, Kang YK, Uronis HE, Lee KW, Ng MC, Enzinger PC, Park SH, Gold PJ, Lacy J, Hochster HS, Oh SC, Kim YH, Marrone KA, Kelly RJ, Juergens RA, Kim JG, Alcindor T, Sym SJ, Song EK, Chee CE, Chao Y, Kim S, Oh DY, Yen J, Odegaard JI, Lagow E, Li D, Sun J, Kaminker P, Moore PA, Rosales MK, Park H. Circulating Tumor DNA as a Predictive Biomarker for Clinical Outcomes With Margetuximab and Pembrolizumab in Pretreated HER2-Positive Gastric/ Gastroesophageal Adenocarcinoma. Oncology (Williston Park). 2023 Apr 25;37(4):176-183. doi: 10.46883/2023.25920992.
PMID: 37104758DERIVEDCatenacci DVT, Kang YK, Park H, Uronis HE, Lee KW, Ng MCH, Enzinger PC, Park SH, Gold PJ, Lacy J, Hochster HS, Oh SC, Kim YH, Marrone KA, Kelly RJ, Juergens RA, Kim JG, Bendell JC, Alcindor T, Sym SJ, Song EK, Chee CE, Chao Y, Kim S, Lockhart AC, Knutson KL, Yen J, Franovic A, Nordstrom JL, Li D, Wigginton J, Davidson-Moncada JK, Rosales MK, Bang YJ; CP-MGAH22-5 Study Group. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial. Lancet Oncol. 2020 Aug;21(8):1066-1076. doi: 10.1016/S1470-2045(20)30326-0. Epub 2020 Jul 9.
PMID: 32653053DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- VP, Scientific Communications
- Organization
- TerSera Therapeutics LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 27, 2016
First Posted
February 23, 2016
Study Start
January 1, 2016
Primary Completion
January 1, 2021
Study Completion
January 1, 2021
Last Updated
March 17, 2025
Results First Posted
August 4, 2022
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will not share