Pembrolizumab in Post Radical Operation ESCC Patients With Lymph Node Positive ( KEYSTONE-004 )

Pembrolizumab for Adjuvant Treatment After R0 Resection of Thoracic ESCC Patients With Lymph Node Positive: A Single-arm, Open-label, PhaseⅡTrial

The purpose of this study is to observe and evaluate the efficacy and safety of postoperative adjuvant treatment of pembrolizumab in patients with thoracic esophageal squamous cell carcinoma （ESCC） who have not received neoadjuvant therapy before undergoing R0 resection, and have positive postoperative lymph nodes.

For patients with thoracic esophageal squamous cell carcinoma （ESCC） who have undergone R0 resection, have not received neoadjuvant therapy, and have positive postoperative lymph nodes, there is no international consensus on whether postoperative adjuvant therapy is required. The JCOG9204 study reported that for patients with ESCC with positive lymph nodes after R0 resection, postoperative adjuvant chemotherapy can improve the disease-free survival (DFS) of the ESCC patients. However, due to the adverse effects of chemotherapy, patients are often difficult to tolerate. We designed a single-arm, open-label, phase II trial of pembrolizumab for adjuvant treatment after R0 resection of thoracic ESCC Patients with lymph node positive. The purpose of this study is to observe and evaluate the efficacy and safety.

Inclusion Criteria:

1. Histologically confirmed ESCC;
2. Patients have not received neoadjuvant therapy.
3. Thoracic ESCC with R0 resection and positive postoperative lymph nodes;
4. Have a performance status of 0 or 1 on the ECOG Performance Scale;
5. Age 18-70 years old, both men and women;
6. Be willing and able to provide written informed consent/assent for the trial;
7. Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation;
8. 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;
9. Be willing to provide postoperative tissue specimens. After tumor recurrence, continue to be willing to provide tissue samples such as needle biopsy.

Exclusion Criteria:

1. Neoadjuvant therapy (radiotherapy, immunotherapy, or chemotherapy) for ESCC;
2. Non-R0 resection for ESCC;
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 pembrolizumab and/or any PD-1/PD-L1 inhibitors.