Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer

NCT ID: NCT02689284

Last Updated: 2025-03-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2021-01-31

Brief Summary

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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

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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.

Conditions

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Gastric Cancer Stomach Cancer Esophageal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg

margetuximab administered in combination with pembrolizumab

Group Type EXPERIMENTAL

Margetuximab 10 mg/kg

Intervention Type BIOLOGICAL

Margetuximab treatment is administered intravenously (IV) once every 21-day cycle

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab treatment is administered IV once every 21-day cycle

Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg

margetuximab administered in combination with pembrolizumab

Group Type EXPERIMENTAL

Margetuximab 15 mg

Intervention Type BIOLOGICAL

Margetuximab treatment is administered IV once every 21-day cycle

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab treatment is administered IV once every 21-day cycle

Interventions

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Margetuximab 10 mg/kg

Margetuximab treatment is administered intravenously (IV) once every 21-day cycle

Intervention Type BIOLOGICAL

Margetuximab 15 mg

Margetuximab treatment is administered IV once every 21-day cycle

Intervention Type BIOLOGICAL

Pembrolizumab

Pembrolizumab treatment is administered IV once every 21-day cycle

Intervention Type BIOLOGICAL

Other Intervention Names

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MGAH22 MGAH22 MK-3475

Eligibility Criteria

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Inclusion Criteria

1. Signed written informed consent.
2. Age ≥ 18 years old (or minimum age based upon local regulations)
3. 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.
4. HER2+ as 3+ (as defined in AJCC staging manual 8th edition) by IHC or in-situ hybridation (ISH) amplified.
5. Have received prior treatment with trastuzumab.
6. Have received treatment with at least one or more lines of cytotoxic chemotherapy in the metastatic setting.
7. Resolution of chemotherapy, immunotherapy or radiation-related toxicities.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Life expectancy ≥ 12 weeks.
10. Measurable disease as per RECIST 1.1 criteria.

Exclusion Criteria

1. Patients with symptomatic central nervous system (CNS) metastases.
2. Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
3. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
4. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.
5. Treatment with radiation therapy within 3 weeks prior to the initiation of study drug administration.
6. 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.
7. History of clinically-significant cardiovascular disease.
8. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
9. History of (non-infectious) pneumonitis that required steroids or presence of active pneumonitis
10. Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
11. Evidence of active viral, bacterial, or systemic fungal infection.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

MacroGenics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Yale School of Medicine

New Haven, Connecticut, United States

Site Status

Georgetown University-Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Johns Hopkins University Medical Center

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute/Harvard University Medical Center

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Juravinski Cancer Centre - McMaster University

Hamilton, Ontario, Canada

Site Status

McGill University Health Centre

Montreal, Quebec, Canada

Site Status

National Cancer Centre

Singapore, , Singapore

Site Status

National University Hospital

Singapore, , Singapore

Site Status

Raffles Hospital

Singapore, , Singapore

Site Status

Kyungbuk National University Hospital

Daegu, , South Korea

Site Status

Gachon University Gil Medical Center

Incheon, , South Korea

Site Status

Chonbuk National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul National University Bundang Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Canada Singapore South Korea Taiwan

References

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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.

Reference Type DERIVED
PMID: 37104758 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32653053 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CP-MGAH22-05

Identifier Type: -

Identifier Source: org_study_id

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