Study of SHR-1210 in Combination With Chemotherapy in Advanced Esophageal Cancer

PD-1 Antibody SHR-1210 Combined With Paclitaxel and Cisplatin Versus Placebo Combined With Paclitaxel and Cisplatin as First-line Therapy for Advanced Esophageal Cancer: a Randomized, Double-blinded, Controlled, Multi-center Phase III Trial

This is a randomised, double-blinded, placebo-controlled, multi-center phase III trial, comparing the efficacy and safety of SHR-1210 + paclitaxel + cisplatin vs placebo+paclitaxel +cisplatin as 1L therapy for advanced esophageal cancer patients in China. SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.

Study Overview

• Status: Completed
• Conditions: Advanced Esophageal Cancer
• Intervention / Treatment: Drug: Placebo; Drug: SHR-1210; Drug: paclitaxel; Drug: cisplatin

Detailed Description

In this study, eligible subjects will be randomized into study arm or control arm. Treatment cycles of chemotherapy will be at most 6 cycles which would be decided by the investigators. Progression-free survival (PFS) assessed by the Independent Review Committee (IRC) and overall survival (OS) will be the primary outcomes.

• Study Type: Interventional
• Enrollment (Actual): 596
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center of Sun-Yat Sen University (CCSYSU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed unresectable local advanced/recurrent or metastasis esophageal squamous cell carcinoma;
2. No previous systemic anti-tumor treatment;
3. Subjects must have at least one measurable tumor lesion per RECIST 1.1;
4. Tissue samples should be provided for biomarkers (such as PD-L1) analysis;
5. ECOG: 0-1;
6. Adequate organ and bone marrow function;

Exclusion Criteria:

1. Allergic to monoclonal antibodies, any SHR-1210 components, paclitaxel, cisplatin and other platinum drugs;

2. Prior therapy as follow:

   1. Anti-PD-1 or anti-PD-L1;
   2. Any experimental drugs within 4 weeks of the first dose of study medication;
   3. Received major operations or serious injuries within 4 weeks of the first dose of study medication;
   4. Received last dose of anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, etc.) within 4 weeks of the first dose of study medication;
3. Not recovered to ≤CTCAE 1 from adverse events (except for hair loss) due to a previously anti-tumor treatment;
4. Subjects with any active autoimmune disease or history of autoimmune disease;
5. Pregnancy or breast feeding;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1210 + paclitaxel + cisplatin; Paclitaxel 175mg/m2, Day 1，cisplatin 75mg/m2，Day 1，SHR-1210 200mg，Day 2，every 3 weeks, maximum 6 cycles, then SHR-1210 maintenance	Drug: SHR-1210; SHR-1210 200mg; Other Names: camrelizumab; Drug: paclitaxel; paclitaxel 175mg/m2; Drug: cisplatin; cisplatin 75mg/m2
Active Comparator: placebo+paclitaxel + cisplatin; Paclitaxel 175mg/m2, Day 1，cisplatin 75mg/m2，Day 1，placebo，Day 2，every 3 weeks, maximum 6 cycles, then placebo maintenance	Drug: Placebo; Placebo; Drug: paclitaxel; paclitaxel 175mg/m2; Drug: cisplatin; cisplatin 75mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by IRC	based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1)	approximately 22 months
OS	OS is defined as the time from registration to death due to any cause, or censored at date last known alive. Measured by the method of Kaplan and Meier.	approximately 22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by investigators	based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1)	approximately 22 months
6 and 9 month OS rate	OS is defined as the time from registration to death due to any cause, or censored at date last known alive. Measured by the method of Kaplan and Meier.	approximately 6 and 9 months
ORR	based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1)	approximately 22 months
DCR	based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1)	approximately 22 months
DoR	based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1)	approximately 22 months
AE	adverse events	approximately 22 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antidrug Antibodies (ADAs)	To evaluate the incidence of ADAs against SHR-1210	approximately 22 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Ruihua Xu, Cancer Center of Sun-Yat Sen University (CCSYSU); Study Director: Qing Yang, Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: September 21, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Estimate): December 7, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: cisplatin; paclitaxel; PD-1Antibody; advanced esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: SHR-1210-III-306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No