Perioperative Toripalimab (JS001) Combined With Neoadjuvant Chemotherapy in Patients With Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This is a randomized, placebo-controlled, multi-center, double-blinded, Phase III study to determine the efficacy and safety of patients with locally advanced squamous cell carcinoma of the thoracic esophagus treated with perioperative immunotherapy combined with neoadjuvant chemotherapy versus placebo combined with neoadjuvant chemotherapy.

Official Title
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A Phase III Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Perioperative Toripalimab (JS001) Combined With Neoadjuvant Chemotherapy in Patients With Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Conditions
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Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Combination Product: Toripalimab combined with cisplatin and paclitaxel
* Combination Product: Placebo combined with cisplatin and paclitaxel


Participation Criteria
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Eligibility Criteria
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Patients must fulfill all of the following inclusion criteria to be eligible for enrollment in this study: Histologically confirmed locally advanced (T1N1-3M0 or T2-3N0-3M0) squamous cell carcinoma of the thoracic esophagus (per the 8th Edition of UICC-TNM Classification); No suspicious cervical lymph node metastasis on cervical contrast-enhanced CT; no systemic metastasis from radiological examination; Expected to be achievable to conduct R0 resection. Patients must not enter this study if any of the following exclusion criteria is fulfilled: Having malignant tumors other than esophageal carcinoma within 5 years prior to randomization; Combined with other inoperable condition; Previous serious allergy to chemotherapeutic agents (paclitaxel or cisplatin) or any monoclonal antibody; Combined with other conditions unsuitable for participation in this study as judged by investigators. Other protocol defined Inclusion/exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental Group<br>Toripalimab combined with cisplatin and paclitaxel | Combination Product: Toripalimab combined with cisplatin and paclitaxel<br>* Specified doses on specified days.<br>|
| Placebo Comparator: Control Group<br>Placebo combined with cisplatin and paclitaxel | Combination Product: Placebo combined with cisplatin and paclitaxel<br>* Specified doses on specified days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare IRC-assessed events-free survival (EFS) in 2 arms |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologically complete remission (pCR) rate | To compare the percentage of patients who achieved pCR in the 2 arms, pCR rate was defined as the percentage of subjects who achieved a complete pathological response (PCR) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 60 months | 
| Investigator-assessed EFS according to RECIST v1.1 | To compare Investigator-assessed events-free survival (EFS) in patients with locally advanced squamous cell carcinoma of the thoracic esophagus treated with perioperative immunotherapy combined with neoadjuvant chemotherapy versus placebo combined with neoadjuvant chemotherapy. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 60 months | 
| Overall survival | To compare Overall survival in patients with locally advanced squamous cell carcinoma of the thoracic esophagus treated with perioperative immunotherapy combined with neoadjuvant chemotherapy versus placebo combined with neoadjuvant chemotherapy. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 60 months | 
| 1-year OS rate | To compare 1-year OS rates in patients with locally advanced squamous cell carcinoma of the thoracic esophagus treated with perioperative immunotherapy combined with neoadjuvant chemotherapy versus placebo combined with neoadjuvant chemotherapy | from randomization to death from any cause at 1 year | 
| 3- year OS rate | To compare 3-year OS rates in patients with locally advanced squamous cell carcinoma of the thoracic esophagus treated with perioperative immunotherapy combined with neoadjuvant chemotherapy versus placebo combined with neoadjuvant chemotherapy | from randomization to death from any cause at 3 year | 
| 5- year OS rate | To compare 5-year OS rates in patients with locally advanced squamous cell carcinoma of the thoracic esophagus treated with perioperative immunotherapy combined with neoadjuvant chemotherapy versus placebo combined with neoadjuvant chemotherapy | from randomization to death from any cause at 5 year |