Clinical trial NCT03958890: 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)
Official title: A Randomized, Double-blind, Multicenter, Phase III Clinical Trial Comparing HLX10 (Recombinant Anti-pd-1 Humanized Monoclonal Antibody Injection) With Placebo Combined With Chemotherapy (Cisplatin + 5-fu) in the First-line Treatment of Locally Advanced/Metastatic Esophageal Squamous Cell Carcinoma (ESCC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2019-05-22
Enrollment: 489
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: PFS
timeFrame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
measure: OS
timeFrame: from the date of first dose unitl the date of death from any cause，assessed up to 2 years
Secondary outcomes:
measure: PFS
timeFrame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
measure: ORR
timeFrame: up to 2 years
measure: Duration of response
timeFrame: from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier),assessed up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Ethics Committeeof cancer hospital, Chinese academy of medical sciences,
state: Beijing
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Ha'erbin
country: China
facility: Affiliated Tumor Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: The first Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Xuzhou
country: China
facility: the affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Changchun
country: China
facility: the second Hospital of Jilin University
state: Jilin
Study officials:
References: