Clinical Trials /

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

NCT02689284

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Combination Margetuximab and <span class="go-doc-concept go-doc-intervention">Pembrolizumab</span> for Advanced, Metastatic <span class="go-doc-concept go-doc-biomarker">HER2</span>(+) Gastric or Gastroesophageal Junction Cancer

Title

  • 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
  • Clinical Trial IDs

    NCT ID: NCT02689284

    ORG ID: CP-MGAH22-05

    Trial Conditions

    Gastric Cancer

    Stomach Cancer

    Esophageal Cancer

    Trial Interventions

    Drug Synonyms Arms
    margetuximab in combination with pembrolizumab Dose Escalation Phase, Dose Expansion Phase

    Trial 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.

    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.

    Trial Arms

    Name Type Description Interventions
    Dose Escalation Phase Experimental Determine the MTD or MAD (if no MTD is defined) of escalating doses of margetuximab administered in combination with pembrolizumab margetuximab in combination with pembrolizumab
    Dose Expansion Phase Experimental Determine safety and activity of margetuximab and pembrolizumab combination dose (as determined from the Dose Escalation Phase) margetuximab in combination with pembrolizumab

    Eligibility 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/L, ANC 1.5 x 103/L, 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Determine the recommended expansion phase dose of margetuximab in combination with pembrolizumab

    Anti-Tumor Activity

    Anti-Tumor Activity

    Secondary Outcome Measures

    Overall Survival (OS)

    Progression Free Survival (PFS)

    Trial Keywords

    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