SHR-1701 in Combination With Irinotecan Liposome (II) for Second-line Treatment of ESCC After Immunotherapy

The Efficacy, Safety and Feasibility of SHR-1701 in Combination With Irinotecan Liposome (II) for Second-line Treatment of Esophageal Squamous Cell Carcinoma After Immunotherapy

This study is a single-arm, exploratory clinical trial aimed at evaluating the efficacy and safety of SHR-1701 in combination with liposomal irinotecan (II) in patients with esophageal squamous cell carcinoma who have received prior immunotherapy. Eligible patients with esophageal cancer will be treated with SHR-1701 in combination with liposomal irinotecan (II).

Inclusion Criteria:

1. Signed written informed consent, voluntarily participating in this study;

2. Histopathologically or cytologically confirmed esophageal squamous cell carcinoma;

3. Prior treatment with immunotherapy;

4. At least one measurable lesion as assessed by RECIST version 1.1;

5. Age ≥ 18 years, male or female;

6. ECOG performance status of 0 or 1;

7. Life expectancy > 3 months;

8. Adequate organ function:

   1. Hematology: Neutrophils ≥ 1.5 × 10^9/L, Hemoglobin ≥ 9 g/dL, Platelets ≥ 100 × 10^9/L.
   2. Hepatic function: Bilirubin ≤ 1.5 × the upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin ≤ 3 × ULN are eligible); AST and ALT ≤ 2.5 × ULN (if liver metastases are present, AST/ALT ≤ 5 × ULN); Alkaline phosphatase ≤ 3 × ULN (if liver or bone metastases are present, ALP ≤ 5 × ULN); Albumin ≥ 3 g/dL.
   3. Renal function: Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate by Cockcroft-Gault: Creatinine clearance ≥ 60 mL/min.
   4. Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

9. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose, must not be breastfeeding, and must agree to use effective contraception for 6 months after the last dose; for male patients with a partner of childbearing potential, effective contraception must be used for 3 months after the last dose; sperm donation is not permitted during the study;

10. Patients are well compliant and agree to cooperate with follow-up.

Exclusion Criteria:

• 1. Active or untreated central nervous system (CNS) metastases (e.g., brain or leptomeningeal metastases) as determined by CT or magnetic resonance imaging (MRI) assessment during screening.

  2. Uncontrolled tumor-related pain. 3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently); patients with an indwelling catheter (e.g., PleurX®) are permitted.

  4. History of a malignancy other than esophageal cancer within 5 years prior to enrollment, except for malignancies with a negligible risk of metastasis or death (e.g., expected 5-year overall survival > 90%) and those that are expected to be cured after treatment.

  5. History of allergy to monoclonal antibodies, liposomal products, or irinotecan.

  6. Prior or current receipt of any of the following therapies:

  1. Use of immunosuppressive medications or systemic corticosteroid therapy for immunosuppressive purposes (dose > 10 mg/day prednisone or equivalent) within 2 weeks prior to the first dose of study drug; inhaled or topical steroids and adrenal corticosteroid replacement at doses > 10 mg/day prednisone or equivalent are permitted in the absence of active autoimmune disease.

  2. Receipt of a live attenuated vaccine within 4 weeks prior to the first dose of study drug.

  3. Major surgery or significant traumatic injury within 4 weeks prior to the first dose of study drug.

     7. Any active autoimmune disease or a history of autoimmune disease. 8. History of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.

     9. Presence of poorly controlled cardiac clinical symptoms or diseases. 10. Occurrence of a severe infection within 4 weeks prior to the first dose of study drug.

     11. Active pulmonary tuberculosis infection as identified by medical history or CT examination.

     12. Active hepatitis B (HBV DNA ≥ 200 IU/mL or ≥ 1000 copies/mL or ≥ the upper limit of normal), or hepatitis C (positive hepatitis C antibody and HCV RNA above the lower limit of quantification of the assay).

     13. Pregnant or breastfeeding women. 14. Any other condition judged by the investigator that could lead to forced discontinuation from the study, such as other serious illnesses (including mental illnesses) requiring concomitant treatment, alcoholism, drug abuse, family or social factors, or factors that could affect patient safety or compliance.