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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02689284
Recruitment Status : Active, not recruiting
First Posted : February 23, 2016
Last Update Posted : October 9, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
MacroGenics

Study Description
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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.

Condition or disease Intervention/treatment Phase
Gastric Cancer Stomach Cancer Esophageal Cancer Biological: Margetuximab plus pembrolizumab Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Margetuximab plus pembrolizumab
margetuximab administered in combination with pembrolizumab
 Biological: Margetuximab plus pembrolizumab
margetuximab in combination with pembrolizumab; combination treatment is administered once every 21-day cycle
Other Name: Keytruda


Outcome Measures
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Primary Outcome Measures :
  1. Determine the recommended expansion phase dose of margetuximab in combination with pembrolizumab [ Time Frame: 9 months ]
    Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab when administered in combination with pembrolizumab

  2. Anti-Tumor Activity [ Time Frame: 12 months ]
    Investigate the preliminary anti-tumor activity as measured by response duration of margetuximab when administered in combination with pembrolizumab, using both conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRC).

  3. Anti-Tumor Activity [ Time Frame: 12 Months ]
    Investigate the preliminary anti-tumor activity, as measured by objective response rate (ORR) of margetuximab when administered in combination with pembrolizumab, using conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRC).


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 24 Months ]
    To investigate the preliminary effect of the combination treatment on OS

  2. Progression Free Survival (PFS) [ Time Frame: 24 Months ]
    To investigate the preliminary effect of the combination treatment on PFS


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689284


Locations
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Sponsors and Collaborators
MacroGenics
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Minori Rosales, M.D., PhD MacroGenics
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02689284    
Other Study ID Numbers: CP-MGAH22-05
First Posted: February 23, 2016    Key Record Dates
Last Update Posted: October 9, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by MacroGenics:
Stomach Cancer
Gastroesophageal Junction
Gastric Cancer
Cancer of the Stomach
Cancer of Stomach
Stomach
Pembrolizumab
Keytruda
HER2+
GEJ
HER2 positive
Metastatic
Margetuximab
 Immunotherapy
Trastuzumab
Human epidermal growth factor receptor 2
Human epidermal growth factor receptor 2-positive
gastroesophageal junction cancer
Pembro
PD-L1
PD-1
PD
Tumor
Cancer
KEYNOTE MK3475-PN197
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
 Gastrointestinal Diseases
Stomach Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents