Back to resultsCombination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
Primary Purpose
Gastric Cancer, Stomach Cancer, Esophageal Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Margetuximab 10 mg/kg
Margetuximab 15 mg
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Yale School of Medicine
- Georgetown University-Lombardi Comprehensive Cancer Center
- University of Chicago
- Johns Hopkins University Medical Center
- Dana-Farber Cancer Institute/Harvard University Medical Center
- Karmanos Cancer Institute
- Washington University School of Medicine
- Duke University Medical Center
- Fox Chase Cancer Center
- Sarah Cannon Research Institute
- Swedish Cancer Institute
- Juravinski Cancer Centre - McMaster University
- McGill University Health Centre
- Kyungbuk National University Hospital
- Gachon University Gil Medical Center
- Chonbuk National University Hospital
- Asan Medical Center
- Korea University Anam Hospital
- Korea University Guro Hospital
- Samsung Medical Center
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- National Cancer Centre
- National University Hospital
- Raffles Hospital
- National Taiwan University Hospital
- Taipei Veterans General Hospital
- Tri-Service General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg
Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg
Arm Description
margetuximab administered in combination with pembrolizumab
margetuximab administered in combination with pembrolizumab
Outcomes
Primary Outcome Measures
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
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
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
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).
Duration of Response
Duration of response is calculated at the time from CR or PR to relapse or cancer progression.
Secondary Outcome Measures
Overall Survival (OS)
The median length of time between first dose of study medication and death from any cause.
Progression Free Survival (PFS)
The interval between the first dose of study medication and progression of disease or death from any cause.
Change From Baseline in Pharmacodynamic Markers in Whole Blood
The planned assessment included examination of markers of T-cell activation
Analysis of HER2 Tumor Cell Membrane Expression in Biopsy Specimens Before and After Treatment
Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab (Immunogenicity)
Maximum Concentration of Margetuximab at Steady State
Measurement of PK characteristics is limited to margetuximab. No analysis of pembrolizumab was conducted.
Area Under the Concentration Time Curve at Steady State (AUC ss)
AUC is a mathematical calculation that describes the variation in drug concentration in the blood over time.
Clearance
Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time.
Volume of Distribution at Steady State
The volume of distribution is related to a whether how much drug is distributed to body tissues, or remains in the bloodstream.
Terminal Half-life
Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
Full Information
NCT ID
NCT02689284
First Posted
January 27, 2016
Last Updated
July 11, 2022
Sponsor
MacroGenics
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02689284
Brief Title
Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
January 2021 (Actual)
Study Completion Date
January 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MacroGenics
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
Detailed Description: Both margetuximab and pembrolizumab are monoclonal antibodies used in combination to treat HER2+ gastric and gastroesophageal junction cancer. This study has two parts: Dose Escalation and Dose Expansion. The Dose Escalation phase of the study will evaluate safety of escalating doses of the combination treatment. The Dose Expansion phase will evaluate safety and activity of the combination in patients with gastric or gastroesophageal cancer once the final dose and schedule are defined. In addition, a cohort of patients with HER2+ 3+ gastric cancer patients will be enrolled in the Dose Expansion Phase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Stomach Cancer, Esophageal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg
Arm Type
Experimental
Arm Description
margetuximab administered in combination with pembrolizumab
Arm Title
Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg
Arm Type
Experimental
Arm Description
margetuximab administered in combination with pembrolizumab
Intervention Type
Biological
Intervention Name(s)
Margetuximab 10 mg/kg
Other Intervention Name(s)
MGAH22
Intervention Description
Margetuximab treatment is administered intravenously (IV) once every 21-day cycle
Intervention Type
Biological
Intervention Name(s)
Margetuximab 15 mg
Other Intervention Name(s)
MGAH22
Intervention Description
Margetuximab treatment is administered IV once every 21-day cycle
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
Pembrolizumab treatment is administered IV once every 21-day cycle
Primary Outcome Measure Information:
Title
Number of Patients With Dose Limiting Toxicities
Description
Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab when administered in combination with pembrolizumab
Time Frame
21 days
Title
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).
Description
The number of patients that experience either an AE or a SAE during the study participation
Time Frame
up to 24 months
Title
Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment
Description
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
Time Frame
12 months
Title
Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment Using irRC Criteria
Description
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).
Time Frame
12 Months
Title
Duration of Response
Description
Duration of response is calculated at the time from CR or PR to relapse or cancer progression.
Time Frame
up to 24 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
The median length of time between first dose of study medication and death from any cause.
Time Frame
24 Months
Title
Progression Free Survival (PFS)
Description
The interval between the first dose of study medication and progression of disease or death from any cause.
Time Frame
24 Months
Title
Change From Baseline in Pharmacodynamic Markers in Whole Blood
Description
The planned assessment included examination of markers of T-cell activation
Time Frame
from first dose to the end of treatment, average about 12 months
Title
Analysis of HER2 Tumor Cell Membrane Expression in Biopsy Specimens Before and After Treatment
Time Frame
from first dose to the end of treatment, average 12 months.
Title
Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab (Immunogenicity)
Time Frame
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
Title
Maximum Concentration of Margetuximab at Steady State
Description
Measurement of PK characteristics is limited to margetuximab. No analysis of pembrolizumab was conducted.
Time Frame
At end of infusion on Cycle 1, Day 1. Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months
Title
Area Under the Concentration Time Curve at Steady State (AUC ss)
Description
AUC is a mathematical calculation that describes the variation in drug concentration in the blood over time.
Time Frame
Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months
Title
Clearance
Description
Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time.
Time Frame
Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months.
Title
Volume of Distribution at Steady State
Description
The volume of distribution is related to a whether how much drug is distributed to body tissues, or remains in the bloodstream.
Time Frame
Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit average 12 months .
Title
Terminal Half-life
Description
Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
Time Frame
Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit average 12 months .
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen L Eck, M.D., PhD
Organizational Affiliation
MacroGenics
Official's Role
Study Director
Facility Information:
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Georgetown University-Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Johns Hopkins University Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Dana-Farber Cancer Institute/Harvard University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Juravinski Cancer Centre - McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V5C2
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada
Facility Name
Kyungbuk National University Hospital
City
Daegu
ZIP/Postal Code
41404
Country
Korea, Republic of
Facility Name
Gachon University Gil Medical Center
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Facility Name
Chonbuk National University Hospital
City
Seoul
ZIP/Postal Code
54907
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Korea University Anam Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
National Cancer Centre
City
Singapore
Country
Singapore
Facility Name
National University Hospital
City
Singapore
Country
Singapore
Facility Name
Raffles Hospital
City
Singapore
Country
Singapore
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
Country
Taiwan
Facility Name
Tri-Service General Hospital
City
Taipei
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32653053
Citation
Catenacci 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.
Results Reference
derived
Learn more about this trial
Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
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