A Clinical Trial Comparing HLX10 With Placebo Combined With Chemotherapy (Cisplatin + 5-fu) in the First-line Treatment of Locally Advanced/Metastatic Esophageal Squamous Cell Carcinoma (ESCC)

NCT ID: NCT03958890

Last Updated: 2023-04-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 489 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-19
• Study Completion Date: 2023-12-30

Brief Summary

This study is a randomized, double-blind, multi-center, phase III clinical study comparing the clinical efficacy and safety of HLX10 or placebo combined with chemotherapy in first-line treatment of locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) patients.This study consists of three periods, screening period (28 days), treatment period and follow-up period (including safety follow-up, survival follow-up).Subjects can be enrolled into this study only if they meet inclusion criteria and do not meet exclusion criteria.

Conditions

Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

HLX10

Group Type: EXPERIMENTAL

HLX10 100 mg in 10 ml Injection

Intervention Type: DRUG

3mg/kg IV（HLX10+cis-platinum+5FU）

placebo

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

3mg/kg IV（placebo+cis-platinum+5FU）

Interventions

HLX10 100 mg in 10 ml Injection

3mg/kg IV（HLX10+cis-platinum+5FU）

Intervention Type: DRUG

Placebos

3mg/kg IV（placebo+cis-platinum+5FU）

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects who meet all of the following criteria are allowed to be enrolled into this study:

• Volunteer to participate in this clinical study; completely understand and know this study as well as sign the informed consent form (ICF); be willing to follow and be able to complete all study procedures;
• Age ≥ 18 years and ≤ 75 years when ICF is signed;
• Never received systemic anti-tumor drug therapy before.Exception: for patients who have received neoadjuvant/adjuvant treatment, the time from the last treatment to recurrence or progression can be screened for more than 6 months;For patients who have received radical concurrent chemoradiotherapy or radiotherapy for esophageal cancer, the time from the last chemotherapy/radiotherapy to the recurrence or progression time is more than 12 months.
• According to the curative effect evaluation criteria in solid tumors (RECIST) v1.1, assessed by the center image with at least one measurable lesions (such as esophageal cavity structure not as measurable lesions), measurable lesions should be not received radiotherapy, etc (lesions located in the usual radiation area, if confirm progress, can also be selected as the target lesion);
• PD-L1 positive subjects (CPS 1%).The subject must provide tumor tissue for pd-l1 expression level determination;
• Within 7 days before the first use of the study drug, ECOG: 0 ~ 1;
• Expected survival 12 weeks;
• The functions of the vital organs meet the following requirements (no blood transfusion, cytokine growth factor, or platelet raising drugs are allowed within 14 days before the first use of the study drugs); H. Absolute neutrophil count (ANC) ≥1.5 109/L I. platelet≥ 100 109/L; J. Hemoglobin≥ 9g/dL; K. Serum albumin≥ 3.0g/dL; L. Total bilirubin≤ 1.5 ULN, ALT, AST and/or ALP≤ 2.5 ULN;ALT and/or AST≤ 5 ULN in the presence of liver metastasis;If there is liver metastasis or bone metastasis ALP≤ 5 ULN; M. Serum creatinine ≤1.5 ULN or creatinine clearance > 60 mL/min (Cockcroft-Gault formula); N. APTT, INR and PT ≤1.5 ULN;
• For fertile female subjects, the serum pregnancy test must be negative within 7 days before the first dose.With fertile women subjects, and the partner for childbearing age women of male subjects, needs during the therapy, and after the last use HLX10 / placebo at least 3 months and the last time to use at least 6 months after chemotherapy using an approved by the medical contraception (such as intrauterine device, the pill or condoms);
• Subjects voluntarily participated in this study and signed the informed consent, with good compliance and follow-up.

Exclusion Criteria

• Subjects who meet any of the following criteria are not allowed to be enrolled in this study:

• 1. BMI < 17.5kg /m2;
• 2. A history of gastrointestinal perforation and/or fistula within 6 months prior to the first administration;
• 3. Obvious invasion of tumor into adjacent organs (aorta or trachea) of esophageal lesions leads to high risk of bleeding or fistula;3. Subjects after endotracheal stent implantation;
• 4. Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage;
• 5. Previous allergies to monoclonal antibody, HLX10, 5-fu, cisplatin and other platinum drugs;
• 6.Have received any of the following treatments: A. Previous treatment with anti-pd-1 or anti-pd-L1 antibodies; B. Have received any research drugs within 4 weeks before the first use of the study drugs; C. Be enrolled in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or a follow-up interventional clinical study; D. Receive the final anticancer treatment within 4 weeks before the first use of the study drug;Palliative radiotherapy for bone metastases was allowed and was completed 2 weeks before the first dose.Radiotherapy covering more than 30% of the bone marrow area is not allowed within 28 days before the first dose.

E. Subjects who require systemic treatment with corticosteroids (> 10 mg/ day prednisone therapeutic dose) or other immunosuppressive agents within 14 days prior to the first use of the study drug;In the absence of active autoimmune disease, inhalation or topical use of steroids is permitted, and the therapeutic dose of prednisone 10mg/ day is allowed.

F. Those who have received the anti-tumor vaccine or the live vaccine within 4 weeks before the first dose of the study drug; G. Have undergone major surgery within 28 days prior to the first use of the study drug. Major surgery in this study is defined as requiring at least 3 weeks of postoperative recovery time before being able to receive the surgery treated in this study.Tumor puncture or lymph node biopsy were allowed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Henlius Biotech

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ethics Committeeof cancer hospital, Chinese academy of medical sciences,

Beijing, Beijing Municipality, China

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Affiliated Tumor Hospital of Harbin Medical University

Harbin, Heilongjiang, China

The first Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

the affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

the second Hospital of Jilin University

Changchun, Jilin, China

Countries

China

References

Liu S, Jiang N, Dou L, Li S. Cost-effectiveness analysis of serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive esophageal squamous cell carcinoma in China. Front Immunol. 2023 May 4;14:1172242. doi: 10.3389/fimmu.2023.1172242. eCollection 2023.

Reference Type: DERIVED

PMID: 37215110 (View on PubMed)

Song Y, Zhang B, Xin D, Kou X, Tan Z, Zhang S, Sun M, Zhou J, Fan M, Zhang M, Song Y, Li S, Yuan Y, Zhuang W, Zhang J, Zhang L, Jiang H, Gu K, Ye H, Ke Y, Li J, Wang Q, Zhu J, Huang J; ASTRUM-007 investigators. First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial. Nat Med. 2023 Feb;29(2):473-482. doi: 10.1038/s41591-022-02179-2. Epub 2023 Feb 2.

Reference Type: DERIVED

PMID: 36732627 (View on PubMed)

Related Links

https://doi.org/10.1038/s41591-022-02179-2

First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial

https://doi.org/10.1016/j.annonc.2022.10.105

First-line serplulimab versus placebo in combination with chemotherapy in PD-L1-positive oesophageal squamous cell carcinoma (ASTRUM-007): A randomised, double-blind, multicentre phase III study

Other Identifiers

HLX10-007-EC301

Identifier Type: -

Identifier Source: org_study_id