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

Phase 2

Recruiting

• Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Toripalimab (240mg day1, Q3W*3cycle)

• Registration Number: NCT06843889
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-18
• Study First Submitted QC: 2025-02-23
• Study First Posted: 2025-02-25
• Status Verified: 2025-04
• Study Start: 2025-04-03
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-16
• Primary Completion: 2027-08-01
• Study Completion: 2028-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Immunotherapy combined with sequential neoadjuvant radiotherapy group	Toripalimab (240mg day1, Q3W*3cycle)	-

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response Rate (pCR)	Perioperative	The absence of residual viable tumor cells in both the primary esophageal tumor and regional lymph nodes after completion of neoadjuvant chemoradiotherapy and surgery, indicating a complete pathological response.

Secondary Outcome Measures

Name	Time	Method
Major Pathological Response Rate (MPR)	Perioperative	A significant reduction in tumor burden, defined as less than 10% residual viable tumor in the surgical specimen following neoadjuvant chemoradiotherapy, reflecting a near-complete response.
Disease-Free Survival (DFS)	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.	The duration from the date of surgery to the first occurrence of disease recurrence, metastasis, or death from any cause, measuring the effectiveness of the treatment in preventing disease progression.
Overall Survival (OS)	From the date of treatment initiation (or diagnosis) to the date of death from any cause,assessed up to 120 months..	The length of time from the start of neoadjuvant treatment until death from any cause, evaluating the long-term survival benefit of the combined therapy.
Adverse Events (AEs)	Monitored throughout the treatment period and during follow-up, an average of 2 years.	Any unfavorable or unintended medical occurrences, including clinical signs, symptoms, or laboratory abnormalities, observed in patients receiving toripalimab combined with neoadjuvant chemoradiotherapy, regardless of causality.

Trial Locations

Locations (1)

Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Baiyun District, China