Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to observe and evaluate the efficacy and safety of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) followed Surgery for locally advanced adenocarcinoma of esophagogastric junction

Detailed Description
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The neoadjuvant chemotherapy/chemoradiotherapy with surgery is the standard treatment in NCCN guideline. But many patients refused or abandon radiotherapy because of the intolerable adverse effects. We designed a single-arm, open-label, phase II trial of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) followed by radical surgery for locally advanced adenocarcinoma of esophagogastric junction. The purpose of this study is to observe and evaluate the efficacy and safety.

Official Title
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Efficacy and Safety of Pembrolizumab Plus Neoadjuvant Chemotherapy With Cisplatin and 5-Fluorouracill Followed by Surgery in Patients With Locally Advanced Adenocarcinoma of Esophagogastric Junction

Conditions
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Adenocarcinoma of Esophagogastric Junction, Neoadjuvant Chemotherapy, Pembrolizumab

Intervention / Treatment
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* Drug: Pembrolizumab Injection [Keytruda]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed AEG, Siewert type I or II; Potentially resectable cT3-4a, any N, M0 (AJCC 8 TNM classification); Have a performance status of 0 or 1 on the ECOG Performance Scale; Age 18-75 years old, both men and women; Be willing and able to provide written informed consent/assent for the trial; Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation; Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. Exclusion Criteria: Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for AEG; Ineligibility or contraindication for esophagectomy; Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug; Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Pembrolizumab+Cisplatin+5-FU<br>Participants receive preoperative pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), cisplatin 80 mg/m^2 IV Q3W, and 5-FU 600 mg/m^2/day IV infusion on Days 1 to 5. There are 3 cycels of preoprative therapy and 3 cycles of postoperative therapy. | Drug: Pembrolizumab Injection [Keytruda]<br>* Neoadjuvant period: pembrolizumab 200mg IV, Q3W with three cycles. Adjuvant period: pembrolizumab 200 mg IV, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic response (MPR) | Viable tumor comprised ≤ 10% of resected tumor specimens | one month after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Time from the enrollment to disease relapse after complete resection or death from any cause | 24 months | 
| Overall survival (OS) | Time from the enrollment to death of any cause | 24 months | 
| Pathologic complete response (pCR) | No tumor residue of resected tumor specimens | one month after surgery |