Pembrolizumab Plus Neoadjuvant Chemotherapy for Locally Advanced EGJ Adenocarcinoma (KEYSTONE-003)

Tianjin Medical University

Status and phase: Unknown; Phase 2

Conditions: Neoadjuvant Chemotherapy; Adenocarcinoma of Esophagogastric Junction; Pembrolizumab

Treatments: Drug: Pembrolizumab Injection [Keytruda]

Study type: Interventional

Funder types: Other

Identifiers

NCT04813523

TianjinCIH20210169

Details and patient eligibility

About

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

Full description

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically confirmed AEG, Siewert type I or II;
2. Potentially resectable cT3-4a, any N, M0 (AJCC 8 TNM classification);
3. Have a performance status of 0 or 1 on the ECOG Performance Scale;
4. Age 18-75 years old, both men and women;
5. Be willing and able to provide written informed consent/assent for the trial;
6. Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
7. 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;
8. 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

1. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for AEG;
2. Ineligibility or contraindication for esophagectomy;
3. 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;
4. 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);
5. Has severe hypersensitivity and adverse events (≥Grade 3) to nivolumab and/or any PD-1/PD-L1 inhibitors.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Experimental: Pembrolizumab+Cisplatin+5-FU

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab Injection [Keytruda]