Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
- Conditions
- Gastric CancerStomach CancerEsophageal Cancer
- Interventions
- Registration Number
- NCT02689284
- Lead Sponsor
- MacroGenics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 95
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg Margetuximab 15 mg margetuximab administered in combination with pembrolizumab Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg Pembrolizumab margetuximab administered in combination with pembrolizumab Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg Margetuximab 10 mg/kg margetuximab administered in combination with pembrolizumab Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg Pembrolizumab margetuximab administered in combination with pembrolizumab
- Primary Outcome Measures
Name Time Method Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs). up to 24 months 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 Using irRC Criteria 12 Months 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).
Number of Patients With Dose Limiting Toxicities 21 days 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 a Complete Response (CR) or Partial Response (PR) to Treatment 12 months 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
Duration of Response up to 24 months Duration of response is calculated at the time from CR or PR to relapse or cancer progression.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 24 Months The median length of time between first dose of study medication and death from any cause.
Terminal Half-life 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 . Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
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 Maximum Concentration of Margetuximab at Steady State 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 Measurement of PK characteristics is limited to margetuximab. No analysis of pembrolizumab was conducted.
Progression Free Survival (PFS) 24 Months 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 from first dose to the end of treatment, average about 12 months The planned assessment included examination of markers of T-cell activation
Clearance 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. Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time.
Volume of Distribution at Steady State 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 . The volume of distribution is related to a whether how much drug is distributed to body tissues, or remains in the bloodstream.
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. Area Under the Concentration Time Curve at Steady State (AUC ss) 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 AUC is a mathematical calculation that describes the variation in drug concentration in the blood over time.
Trial Locations
- Locations (28)
Seoul National University Bundang Hospital
🇰🇷Seoul, Korea, Republic of
Raffles Hospital
🇸🇬Singapore, Singapore
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Dana-Farber Cancer Institute/Harvard University Medical Center
🇺🇸Boston, Massachusetts, United States
Johns Hopkins University Medical Center
🇺🇸Baltimore, Maryland, United States
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Georgetown University-Lombardi Comprehensive Cancer Center
🇺🇸Washington, District of Columbia, United States
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Kyungbuk National University Hospital
🇰🇷Daegu, Korea, Republic of
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
National Cancer Centre
🇸🇬Singapore, Singapore
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Chonbuk National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
National University Hospital
🇸🇬Singapore, Singapore
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Juravinski Cancer Centre - McMaster University
🇨🇦Hamilton, Ontario, Canada
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States