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

Overview

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.

Interventions

• Drug 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.

Primary outcome measures

• Pathological Complete Response Rate (pCR) [Time frame: Perioperative]

Secondary outcome measures (4)

• Major Pathological Response Rate (MPR) [Time frame: Perioperative]
• Disease-Free Survival (DFS) [Time frame: 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) [Time frame: From the date of treatment initiation (or diagnosis) to the date of death from any cause,assessed up to 120 months..]
• Adverse Events (AEs) [Time frame: Monitored throughout the treatment period and during follow-up, an average of 2 years.]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Nanfang Hospital, Southern Medical University — Guangzhou

Publications

• Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10. PMID 22658128
• Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015 Apr 3;348(6230):56-61. doi: 10.1126/science.aaa8172. PMID 25838373
• Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;1 PMID 24332238
• Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. doi: 10.1200/JCO.2002.08.105. PMID 11956258
• Shah MA, Janjigian YY, Stoller R, Shibata S, Kemeny M, Krishnamurthi S, Su YB, Ocean A, Capanu M, Mehrotra B, Ritch P, Henderson C, Kelsen DP. Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium. J Clin Oncol. 2015 Nov 20;3 PMID 26438119
• Day FL, Leong T, Ngan S, Thomas R, Jefford M, Zalcberg JR, Rischin D, McKendick J, Milner AD, Di Iulio J, Matera A, Michael M. Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer. Br J Cancer. 2011 Jan 18;104(2):265-71. doi: 10.1038/sj.bjc.6606051. Epub 2010 Dec 14. PMID 21157450
• Li QQ, Liu MZ, Hu YH, Liu H, He ZY, Lin HX. Definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous esophageal carcinoma. Dis Esophagus. 2010 Apr;23(3):253-9. doi: 10.1111/j.1442-2050.2009.01003.x. Epub 2009 Aug 28. PMID 19732130
• Urba SG, Orringer MB, Ianettonni M, Hayman JA, Satoru H. Concurrent cisplatin, paclitaxel, and radiotherapy as preoperative treatment for patients with locoregional esophageal carcinoma. Cancer. 2003 Nov 15;98(10):2177-83. doi: 10.1002/cncr.11759. PMID 14601087

Identifiers

NCT: NCT06843889 · NFEC-2025-054

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗