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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by MacroGenics
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT02689284
First received: January 27, 2016
Last updated: April 4, 2017
Last verified: April 2017
  Purpose
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 Intervention Phase
Gastric Cancer
Stomach Cancer
Esophageal Cancer
Drug: margetuximab in combination with pembrolizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • 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

  • 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).

  • 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:
  • Overall Survival (OS) [ Time Frame: 24 Months ]
    To investigate the preliminary effect of the combination treatment on OS

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


Estimated Enrollment: 72
Study Start Date: January 2016
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Phase
Determine the MTD or MAD (if no MTD is defined) of escalating doses of margetuximab administered in combination with pembrolizumab
Drug: margetuximab in combination with pembrolizumab
Combination treatment is administered once every 21-day cycle
Experimental: Dose Expansion Phase
Determine safety and activity of margetuximab and pembrolizumab combination dose (as determined from the Dose Escalation Phase)
Drug: margetuximab in combination with pembrolizumab
Combination treatment is administered once every 21-day cycle

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 once the final dose and schedule are defined.
  Eligibility

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

Inclusion Criteria:

  1. Signed written informed consent.
  2. Age ≥ 18 years old.
  3. Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric adenocarcinoma.
  4. HER2+ as 3+ 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.
  11. Archival or newly obtained tissue sample of a tumor lesion.
  12. Adequate organ function as determined by following laboratory parameters:

    1. Heme: Plt Ct ≥ 100 x 103/µL, ANC ≥ 1.5 x 103/µL, and Hemoglobin ≥ 9 g/dL
    2. Chemistry: ALT/AST ≤ 3.0 x ULN, TBili ≤1.5 x ULN, and Cr < 2 mg/dL
  13. Female patients of childbearing potential must have a negative pregnancy test and agree to use two forms of acceptable contraceptive measures from the time of consent through 120 days after discontinuation of study drug administration.
  14. Male patients with partners of childbearing potential must use barrier contraception.

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. 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.
  12. Known positive testing for human immunodeficiency virus (HIV)or history of acquired immune deficiency syndrome (AIDS).
  13. Known history of or positive test for hepatitis B or hepatitis C infection.
  14. Second primary invasive malignancy that has not been in remission for greater than 2 years.
  15. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug or vehicle formulation for margetuximab or pembrolizumab.
  16. Female patient who is breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02689284

Contacts
Contact: Joe Coffie Coffiej@MacroGenics.com

  Show 25 Study Locations
Sponsors and Collaborators
MacroGenics
Merck Sharp & Dohme Corp.
Investigators
Study Director: Jan Davidson, M.D. MacroGenics
Study Director: Naimish Pandya, M.D. MacroGenics
  More Information

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02689284     History of Changes
Other Study ID Numbers: CP-MGAH22-05
Study First Received: January 27, 2016
Last Updated: April 4, 2017
Individual Participant Data  
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

Additional relevant MeSH terms:
Stomach Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 28, 2017