Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

Gastric Cancer Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02901301
• Other study ID #: 4-2016-0190
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 6, 2017
• Est. completion date: October 2021

Study information

• Verified date: April 2021
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: October 2021
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The recommended dose of phase II		4 weeks
Primary	The overall response rate using RECIST 1.1		6 weeks
Secondary	Duration of response		1 year
Secondary	Time to response		6 weeks