A Phase II Study of Toripalimab Combined With Sequential Neoadjuvant Chemoradiotherapy in Patients With Esophageal Squamous Cell Carcinoma

Обзор

This was a single-center, open phase II clinical study. 34 patients with resectable local middle and advanced esophageal squamous cell carcinoma were treated with anti-PD-1 antibody combined with sequential chemoratherapy regimen: Phase I:Toripalimab (240mg day1, Q3W\*2cycle) + clinical routine chemotherapy regimen selected by the investigator; The second stage: Toripalimab (240mg day1, Q3W\*1cycle) + radiotherapy (intensity modulated radiotherapy, 40Gy/20F, 2Gy/F); Surgery was performed 4-6 weeks after completion, and subsequent treatment options were considered after surgery according to MDT discussion. According to the postoperative pathological results, the pathological complete response (pCR) and major response (MPR) were evaluated. The disease-free survival (DFS), overall survival (OS), 1 or 2 years survival rate and adverse reactions were recorded.

Вмешательства

• Препарат Toripalimab (240mg day1, Q3W*3cycle)
  Phase 1: Toripalimab (240mg day1, Q3W\*2cycle) + investigator's choice of clinical conventional chemotherapy; Phase 2: Toripalimab (240mg day1, Q3W\*1cycle) + radiotherapy (intensity modulated radiotherapy, 40Gy/20F, 2Gy/F); Surgery was performed 4-6 weeks after completion, and subsequent treatment options were considered after surgery according to MDT discussion.

Первичные конечные точки

• Pathological Complete Response Rate (pCR) [Срок оценки: Perioperative]

Вторичные конечные точки (4)

• Major Pathological Response Rate (MPR) [Срок оценки: Perioperative]
• Disease-Free Survival (DFS) [Срок оценки: From the date of surgery (or completion of treatment) to the date of the first documented disease recurrence, metastasis, or death from any cause, whichever occurred first,assessed up to 100 months.]
• Overall Survival (OS) [Срок оценки: From the date of treatment initiation (or diagnosis) to the date of death from any cause,assessed up to 120 months..]
• Adverse Events (AEs) [Срок оценки: Monitored throughout the treatment period and during follow-up, an average of 2 years.]

Критерии участия

Критерии включения

• 1: age 18-75 years old, both sexes; 2: esophageal squamous cell carcinoma confirmed by histopathology; 3: T2-4a, N0-3, M0 (AJCC 8th edition) thoracic esophageal cancer patients, resectable by surgical evaluation; 4: initial treatment patients without anti-tumor therapy; 5: expected survival time ≥6 months; 6: ECOG ≤1; 7: There was no history of esophageal perforation, active esophageal bleeding, and no obvious invasion of trachea or thoracic large vessels.

8: The function of vital organs meets the following requirements: white blood cell ≥4.0×109/l, neutrophil ≥1.5×109/l, platelet ≥100.0×109/l, hemoglobin ≥90g/l; Serum albumin ≥2.8g/Dl; Total bilirubin ≤1.5 × ULN, ALT/AST/ AKP≤2.5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance > 60 mL/min; There were no severe organic diseases.

9: FEV1 ≥ 0.8L; 10: Patients were informed about the trial details and signed informed consent.

Критерии исключения

• 1: known to be allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs or their components; 2: currently participating in and receiving other study treatment; 3: previous systemic therapy for esophageal cancer, including systemic chemotherapy, targeted therapy, immunotherapy, etc.

4: patients with active pulmonary tuberculosis (TB) who were receiving anti-TB treatment or received anti-TB treatment within 1 year before screening; 5: uncontrolled or symptomatic hypercalcemia (>1.5mmol/L calcium ion or calcium >12mg/dL or corrected serum calcium >ULN); 6: clinically uncontrolled active infection, including but not limited to acute pneumonia; 7: uncontrolled major seizures or superior vena cava syndrome; 8: previous or current concomitant other malignant tumors (except non-melanoma basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast/cervix, superficial bladder, etc., which were treated radically and had no evidence of disease recurrence) 9: Patients with a history of interstitial pneumonia, idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, evidence of active pneumonia detected by chest CT scan or other moderate to severe lung diseases that seriously affect lung function; 10: known human immunodeficiency virus (HIV) infection (known HIV antibody positive); 11: severe cardiovascular disease, such as New York Heart Association (NYHA) class 2 or higher heart failure, unstable angina, unstable arrhythmia, myocardial infarction or cerebrovascular accident within 6 months before enrollment; 12: received systemic immunosuppressive drugs (i.e., corticosteroids or immunosuppressive drugs) for any active autoimmune disease within 2 years before study entry; 13: received live viral vaccine within 4 weeks before study entry; 14: patients with prior allogeneic stem cell or solid organ transplantation; 15: pregnant or lactating women or women with the possibility of pregnancy before the first medication positive pregnancy test, patients with fertility but unwilling to accept contraceptive measures or their sexual partners unwilling to accept contraceptive measures; 16: any other disease or condition of clinical significance that the investigator believes could affect adherence to the protocol (e.g., history of psychosis or substance abuse), preclude benefit from the study, or prevent informed consent (e.g., drug use and substance abuse), or preclude participation in the study (including but not limited to: Abnormal laboratory results, clinical active diverticulitis, intra-abdominal abscess, intestinal obstruction, and peritoneal carcinomatosis).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Nanfang Hospital, Southern Medical University — Гуанчжоу

Публикации

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Идентификаторы

NCT: NCT06843889 · NFEC-2025-054

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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