Clinical Trials /

Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

NCT02901301

Description:

Gastric cancer is one of the major health problems worldwide, and one of the leading cause of death especially in Asia. Though the cytotoxic chemotherapy is the main treatment option, newer and molecularly targeted agents are recently incorporated to improve the survival outcome. Human epidermal growth factor receptor 2 (HER2, ErbB2) is a transmembrane tyrosine kinase receptor and is overexpressed or amplified in 10-20% of gastric cancer. Recently, Trastuzumab for Gastric Cancer (ToGA) study reported the clinical benefit of trastuzumab for HER2 positive gastric cancer patients. However, because the majority of patients develop intrinsic or acquired resistance within 1 year, elucidating the molecular mechanisms for trastuzumab resistance is warranted to improve the survival outcome of HER2 positive gastric cancer patients. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of "monoclonal antibody, trastuzumab" in solid tumors. Pembrolizumab is a potent and highly selective humanized monoclonal antibody designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Based on strong rationale in exploring the impact of combining trastuzumab with anti-PD-1 inhibitor in HER2 positive cancer, we suggest multicenter phase IB/II study to determine antitumor activity and safety of pembrolizumab in combination with standard treatment (trastuzumab, capecitabine, and cisplatin) in patients with HER2 positive gastric cancer.

Related Conditions:
  • Gastric Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer
  • Official Title: A Phase Ib/II Study of First Line Pembrolizumab in Combination With Trastuzumab, Capecitabine, and Cisplatin in HER2 Positive Gastric Cancer

Clinical Trial IDs

  • ORG STUDY ID: 4-2016-0190
  • NCT ID: NCT02901301

Conditions

  • Gastric Cancer

Interventions

DrugSynonymsArms
Pembrolizumab4 combination
Trastuzumab4 combination
Capecitabine4 combination
Cisplatin4 combination

Purpose

Gastric cancer is one of the major health problems worldwide, and one of the leading cause of death especially in Asia. Though the cytotoxic chemotherapy is the main treatment option, newer and molecularly targeted agents are recently incorporated to improve the survival outcome. Human epidermal growth factor receptor 2 (HER2, ErbB2) is a transmembrane tyrosine kinase receptor and is overexpressed or amplified in 10-20% of gastric cancer. Recently, Trastuzumab for Gastric Cancer (ToGA) study reported the clinical benefit of trastuzumab for HER2 positive gastric cancer patients. However, because the majority of patients develop intrinsic or acquired resistance within 1 year, elucidating the molecular mechanisms for trastuzumab resistance is warranted to improve the survival outcome of HER2 positive gastric cancer patients. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of "monoclonal antibody, trastuzumab" in solid tumors. Pembrolizumab is a potent and highly selective humanized monoclonal antibody designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Based on strong rationale in exploring the impact of combining trastuzumab with anti-PD-1 inhibitor in HER2 positive cancer, we suggest multicenter phase IB/II study to determine antitumor activity and safety of pembrolizumab in combination with standard treatment (trastuzumab, capecitabine, and cisplatin) in patients with HER2 positive gastric cancer.

Trial Arms

NameTypeDescriptionInterventions
4 combinationExperimentalpembrolizumab 200mg, IV, q3weeks, Day 1 trastuzumab 6mg/kg (8mg loading dose), IV, q3weeks, Day 1 capecitabine 1000mg/m2, PO, BID, Day 1-14 cisplatin 80mg/m2 (level 1), IV, q3weeks, Day 1
  • Pembrolizumab
  • Trastuzumab
  • Capecitabine
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          1. HER2 positive advanced gastric cancer

          2. Be willing and able to provide written informed consent/assent for the trial.

          3. Be 19 years of age on day of signing informed consent.

          4. Have measurable disease based on RECIST 1.1.

          5. performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance
             Scale.

          6. Demonstrate adequate organ function

          7. Female subject of childbearing potential should have a negative urine or serum
             pregnancy or be willing to use birth control.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          3. Has a known history of active Bacillus Tuberculosis

          4. Hypersensitivity to pembrolizumab or any of its excipients.

          5. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or
             who has not recovered from adverse events due to agents administered more than 4 weeks
             earlier.

          6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered from adverse events due
             to a previously administered agent.

          7. Has a known additional malignancy that is progressing or requires active treatment
             within 3 years.

          8. Has known active central nervous system metastases and/or carcinomatous meningitis.

          9. Has active autoimmune disease that has required systemic treatment in the past 2 years

         10. Has known history of, or any evidence of active, non-infectious pneumonitis.

         11. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         12. Has known active Hepatitis B or Hepatitis C

         13. Has received a live vaccine within 30 days of planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The recommended dose of phase II
Time Frame:4 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response
Time Frame:1 year
Safety Issue:
Description:
Measure:Time to response
Time Frame:6 weeks
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yonsei University

Last Updated

January 10, 2018