Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

NCT02901301 | Unknown Phase 1 DMC

• 1 other identifier: 4-2016-0190
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• The recommended dose of phase II

  4 weeks

• The overall response rate using RECIST 1.1

  6 weeks

Secondary Outcomes (2)

• Duration of response

  1 year

• Time to response

  6 weeks

Study Arms (1)

4 combination

EXPERIMENTAL

pembrolizumab 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

Drug: Pembrolizumab; Drug: Trastuzumab; Drug: Capecitabine; Drug: Cisplatin

Interventions

Pembrolizumab DRUG

200mg, IV, q3weeks, Day 1

4 combination

Trastuzumab DRUG

6mg/kg (8mg loading dose), IV, q3weeks, Day 1

4 combination

Capecitabine DRUG

1000mg/m2, PO, BID, Day 1-14

4 combination

Cisplatin DRUG

80mg/m2 (level 1), IV, q3weeks, Day 1

4 combination

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HER2 positive advanced gastric cancer
• Be willing and able to provide written informed consent/assent for the trial.
• Be 19 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
• Demonstrate adequate organ function
• Female subject of childbearing potential should have a negative urine or serum pregnancy or be willing to use birth control.

You may not qualify if:

• 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.
• 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.
• Has a known history of active Bacillus Tuberculosis
• Hypersensitivity to pembrolizumab or any of its excipients.
• 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.
• 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.
• Has a known additional malignancy that is progressing or requires active treatment within 3 years.
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has known active Hepatitis B or Hepatitis C
• Has received a live vaccine within 30 days of planned start of study therapy.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Related Publications (2)

• Jung SH, Lee CK, Kwon WS, Yun S, Jung M, Kim HS, Chung HC, Chung YJ, Rha SY. Monitoring the Outcomes of Systemic Chemotherapy Including Immune Checkpoint Inhibitor for HER2-Positive Metastatic Gastric Cancer by Liquid Biopsy. Yonsei Med J. 2023 Sep;64(9):531-540. doi: 10.3349/ymj.2023.0096.

  PMID: 37634629 DERIVED

• Lee CK, Rha SY, Kim HS, Jung M, Kang B, Che J, Kwon WS, Park S, Bae WK, Koo DH, Shin SJ, Kim H, Jeung HC, Zang DY, Lee SK, Nam CM, Chung HC. A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer. Nat Commun. 2022 Oct 12;13(1):6002. doi: 10.1038/s41467-022-33267-z.

  PMID: 36224176 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pembrolizumab; Trastuzumab; Capecitabine; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 11, 2016
• First Posted: September 15, 2016
• Study Start: February 6, 2017
• Primary Completion: October 31, 2020
• Study Completion: October 1, 2021
• Last Updated: April 6, 2021

Record last verified: 2021-04

Locations

KR (1)