A Study of CS1001 in Subjects With Esophageal Squamous Cell Carcinoma

A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of CS1001 in Combination With Fluorouracil and Cisplatin (FP) Compared to Placebo in Combination With FP as First-Line Therapy in Subjects With Unresectable Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma (ESCC)

Phase III Study to Investigate the Efficacy and Safety of CS1001 or Placebo in Combination with FP as First-Line Therapy in Subjects with Unresectable Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: CS1001+ Fluorouracil+Cisplatin; Drug: Placebo+ Fluorouracil+Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 540
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • The Second Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • Hefei Second People's Hospital
  • Beijing
    • Beijing, Beijing, China
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing Tsinghua Changgung Hospital
    • Beijing, Beijing, China
      • Peaking University International Hospital
  • Chongqing
    • Chongqing, Chongqing, China
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China
      • Chongqing General Hospital
    • Chongqing, Chongqing, China
      • Special Medical Center of The People's Liberation Army of China
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Cancer Hospital
    • Xiamen, Fujian, China
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Foshan, Guangdong, China
      • The First People's Hospital of Foshan
    • Guangzhou, Guangdong, China
      • Guangdong Provincial Hospital of Traditional Chinese Medicine
    • Guangzhou, Guangdong, China
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangdong, China
      • Cancer Center of Guangzhou Medical University
    • Jiangmen, Guangdong, China
      • Jiangmen Central Hospital
    • Jieyang, Guangdong, China
      • Jieyang People's Hospital
    • Shantou, Guangdong, China
      • Affiliated Tumor Hospital of Shantou University Medical College
    • Zhuhai, Guangdong, China
      • The Fifth Affiliated Hospital of Sun Yat sen University
  • Guangxi
    • Nanning, Guangxi, China
      • Guangxi Medical University Affiliated Tumor Hospital
  • Hainan
    • Haikou, Hainan, China
      • Hainan General Hospital
    • Haikou, Hainan, China
      • The Second Affiliated Hospital of Hainan Medical University
  • Hebei
    • Chengde, Hebei, China
      • Affiliated Hospital of Chengde Medical University
    • Handan, Hebei, China
      • HanDan Central Hospital
    • Shijiazhuang, Hebei, China
      • Shijiazhuang People's Hospital
  • Heilongjiang
    • Haerbin, Heilongjiang, China
      • The Affiliated Tumor Hospital of Harbin Meidical University
  • Henan
    • Anyang, Henan, China
      • Anyang Cancer Hospital
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science And Technology
    • Nanyang, Henan, China
      • Nanyang Central Hospital
    • Nanyang, Henan, China
      • Nanyang First People's Hospital
    • Puyang, Henan, China
      • Puyang Oilfield General Hospital
    • Xinxiang, Henan, China
      • Xinxiang First People's Hospital
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China
      • Henan Provincial People's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China
      • Wuhan Union Hospital
    • Wuhan, Hubei, China
      • Tongji Medical College of HUST, Tongji Medical College Huazhong University of Science and Technology
    • Wuhan, Hubei, China
      • Wuhan Fifth Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China
      • Changzhou Tumor Hospital
    • Huai'an, Jiangsu, China
      • Huai'an first people's hospital
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Cancer Hospital
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
    • Changchun, Jilin, China
      • The Second Hospital of Jilin University
    • Tonghua, Jilin, China
      • Tonghua Central Hospital
  • Liaoning
    • Shenyang, Liaoning, China
      • Liaoning Cancer Hospital and Institute
  • Shandong
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Shandong Cancer Hospital
    • Linyi, Shandong, China
      • Linyi Cancer Hospital
    • Qingdao, Shandong, China
      • The Affiliated Hospital of Qingdao University
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Chest Hospital
    • Shanghai, Shanghai, China, 201203
      • Shanghai East Hospital
  • Shanxi
    • Linfen, Shanxi, China
      • Linfen Central Hospital
    • Taiyuan, Shanxi, China
      • Shanxi Provincial Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital Sichuan University
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
    • Chengdu, Sichuan, China
      • Chengdu Fifith people's hospital
    • Luzhou, Sichuan, China
      • The Affiliated Hospital of Southwest Medical University
    • Suining, Sichuan, China
      • Suining Central Hospital
    • Yibin, Sichuan, China
      • Yibin Second People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China
      • Tianjin Cancer Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China
      • Cancer Hospital affiliated to Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

1. ≥ 18 years and ≤ 75 years on the day of signing informed consent form (ICF).
2. Fully informed of the study, with good compliance and willing to provide written ICF. The ICF must be signed before performing any protocol-related procedure (that is not a part of subject's routine medical care).
3. Subjects with pathohistologically or cytologically confirmed unresectable locally advanced, relapsed or metastatic ESCC (based on American Joint Committee on Cancer [AJCC] Guideline version 8, see Appendix 14.2)
4. Subjects must not be eligible for radical therapy such as radical chemoradiotherapy or surgery.
5. Subjects who have not received any systemic anti-neoplastic therapy as the main regimen for locally advanced or metastatic ESCC. (Subjects who received prior neoadjuvant, adjuvant or radical chemoradiotherapy for ESCC but had relapse or progression of disease 6 months after the completion of these treatments are allowed.)
6. ECOG PS 0 or 1.
7. Life expectancy ≥ 3 months.
8. Subjects have at least one measurable lesion as evaluated by the investigator according to RECIST v1.1, and the baseline imaging assessment must be performed within 28 days prior to the first dose of investigational product. Target lesions in the past radiation fields, if confirmed as radiological progression, are considered as measurable lesions.
9. Palliative treatment (e.g. radiotherapy) for local lesion must be completed ≥ 14 days prior to the first dose of investigational product.
10. Subjects must provide tumor tissue samples (formalin fixed-paraffin embedded [FFPE] tissue block or unstained tumor tissue sections) for biomarker analysis, in order to determine the expression of PD-L1.
11. Subjects must have adequate organ function as assessed in the following laboratory tests (subjects must not receive any blood transfusion or any hematopoietic growth factor within 7 days prior to the test)
12. Female subjects with childbearing potential (unless with documentation of sterilization surgery or being post-menopausal) must have negative serum pregnancy test result at screening. Female subject with childbearing potential (unless with documentation of sterilization surgery or being post-menopausal) or male subjects and their partners must agree to use an effective contraceptive measure from the day of signing ICF till at least 6 months after the last dose of investigational product.

Exclusion criteria

1. Adenocarcinoma, mixture of adenocarcinoma and squamous cell carcinoma, or other pathological type of esophageal cancer.
2. Subjects with active central nervous system (CNS) metastasis and/or carcinomatous meningitis (that is symptomatic, or requires treatment, or no radiological evidence confirming the stability of the lesion within 28 days prior to the first dose of investigational product).
3. With another active primary malignancy in the past 5 years, except local curable cancers that have undergone curative therapy, e.g. basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, prostate cancer in situ, breast cancer in situ or cervical cancer in situ.
4. Known history of positive human immunodeficiency virus (HIV) test result or acquired immunodeficiency syndrome (AIDS).
5. Any severe or uncontrolled systemic disease, e.g., diabetes mellitus or hypertension, that may increase the risk associated with participation in the study or investigational product administration, or compromise subject's ability to receive investigational product, as per investigator's judgment.
6. Subjects who have previously received any treatment of antibody or drug that targets at T-cell coregulatory pathways or immune checkpoint pathways, e.g., antibodies targeting at programmed death receptor-1 (PD-1), programmed death receptor-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), OX-40, CD137, T cell immunoglobulin mucin molecule 3 (TIM-3), lymphocyte activation gene 3 (LAG-3), etc. Subjects who have received cell-based immunotherapy (e.g., cytokine-induced killer cell [CIK], chimeric antigen receptor T cell [CAR-T] immunotherapy, etc.).
7. All toxicities except for alopecia and fatigue that are caused by the prior anti-neoplastic treatment has recovered to Grade 1 (according to National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI CTCAE] v5.0).
8. Subjects with history of allogenic stem cell or solid organ transplantation.
9. Subjects with any condition that in the investigator's opinion are not suitable for participating in this study.

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: CS1001+ Fluorouracil+Cisplatin	Drug: CS1001+ Fluorouracil+Cisplatin; CS1001 1200 mg, intravenous infusion on the first day of each cycle (3 weeks) (Q3W). Fluorouracil: 800 mg/m2/day, continuous intravenous infusion on Day 1 to Day 4 of each cycle Cisplatin: 80 mg/m2, intravenous infusion on the first day of each cycle.
Active Comparator: Placebo+ Fluorouracil+Cisplatin	Drug: Placebo+ Fluorouracil+Cisplatin; Placebo 1200 mg, intravenous infusion on the first day of each cycle (3 weeks) (Q3W). Fluorouracil: 800 mg/m2/day, continuous intravenous infusion on Day 1 to Day 4 of each cycle Cisplatin: 80 mg/m2, intravenous infusion on the first day of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by BICR, or death due to any cause, whichever occurred first.	Approximately 43 months from the time of randomization
Overall survival (OS)	OS was defined as the time from randomization to death due to any cause.	Approximately 43 months from the time of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by investigators according to RECIST v1.1	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by investigators, or death due to any cause, whichever occurred first.	Approximately 43 months from the time of randomization
Objective response rate (ORR) assessed by BICR and investigators according to RECIST v1.1	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) or a Partial Response (PR) per RECIST 1.1.	Approximately 43 months from the time of randomization
Duration of response (DoR) assessed by BICR and investigators according to RECIST v1.1	DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first.	Approximately 43 months from the time of randomization

Collaborators and Investigators

• Sponsor: CStone Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: December 3, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cisplatin; Fluorouracil
• Other Study ID Numbers: CS1001-304

Drug and device information, study documents

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