Esophageal Squamous Cell Carcinoma MedDRA version: 25.1 Level: PT Classification code 10030187 Term: Oesophageal squamous cell carcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10058527 Term: Oesophageal squamous cell carcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 25.1 Level: PT Classifi
Conditions
Interventions
Trade Name: Tyvyt®
Product Name: Sintilimab
Product Code: IBI308
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: SINTILIMAB
CAS Number: 2072873-06-2
Current Sponsor code: IBI308
Concen
Sponsors
Innovent Biologics (Suzhou) Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic ESCC (excluding mixed adenosquamous carcinoma and other histological subtypes). 2. Aged = 18. 3. ECOG PS of 0 or 1. 4. Subject must be unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery. For subjects who have received (neo)adjuvant or definitive chemotherapy/radiochemotherapy, time from the completion of last treatment to disease recurrencne must be > 6 months. 5. Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results. 6. Have at least one measurable lesion as per RECIST v1.1. 7. Adequate organs and bone marrow functions, as defined below: 1) Complete blood count: absolute neutrophil count (ANC) = 1.5 × 109/L, platelet (PLT) count = 100 × 109/L, hemoglobin (HGB) = 9.0 g/dL. Note: Subjects cannot receive blood transfusion, erythropoietin (EPO), or Granulocyte-colony stimulating factor (GSF) within 7 days prior to the blood collection. 2) Hepatic function: total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN in subjects without hepatic metastasis; TBIL = 1.5 × ULN, ALT and AST = 5 × ULN in subjects with hepatic metastasis. 3) Renal function: urine protein =65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. ESCC with endoscopy-confirmed near-complete obstruction requiring interventional therapy. 2. Post stent implantation in the esophagus or trachea with risks of perforation. 3. Received systemic treatment for advanced or metastatic ESCC. 4. Received a Cumulative dose of cisplatin > 300 mg/m2within 12 months to randomization. 5. High risk of hemorrhage or perforations due to tumor invasion in adjacent organs (aorta or trachea), or have fistula formation. 6. Load of hepatic metastasis > 50% of the total liver volume. 7. Received treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug that specifically targets T-cell co-stimulation or immune checkpoint pathways. 8. Enrolled in another interventional clinical study, unless only involved in an observational study (non-interventional) or in the follow-up phase of an interventional study. 9. Received palliative therapy for local lesion within 2 weeks prior to the first dose. 10. Received systemic treatment with Chinese traditional medicines with anti-cancer indications or immunomodulators (including thymosins, interferons, and interleukins) within 2 weeks prior to the first dose of study treatment. 11. Received systemic immunosuppressants within 2 weeks prior to randomization, excluding local use of glucocorticoids administered by nasal, inhaled, or other routes, and systemic glucocorticoids at physiological doses (no more than 10 mg/day of prednisone or equivalents), or glucocorticoids to prevent allergies to contrast media. 12. Received a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or be scheduled to receive live attenuated vaccine during the study period. Note: Seasonal inactivated influenza virus vaccines within 4 weeks prior to the first dose of study treatment are permitted, but attenuated influenza vaccines are not. 13. Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or is scheduled to receive major surgery during the course of the trial. 14. Any toxicity (excluding alopecia, events that are not clinically significant, or asymptomatic laboratory abnormalities) due to prior anti-tumor therapy that has not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 grade 0 or 1 prior to the first dose of study treatment. 15. Known symptomatic central nervous system (CNS) metastasis or carcinomatous meningitis. 16. Clinically significant ascites, including ascites that could be detected on physical examination, has been treated with a prior procedure, or currently requires treatment. Asymptomatic subjects with a small amount of ascitic fluid demonstrated by imaging can be enrolled. 17. Moderate bilateral pleural effusion or large unilateral pleural effusion, or effusion resulting in respiratory dysfunction and requiring drainage. 18. Subjects with bone metastases at risk of paraplegia. 19. Known active autoimmune disease requiring treatment or previous disease history within 2 years (subjects with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment, hypothyroidism only requiring thyroid replacement, or type I diabetes only requiring insulin can be enrolled). 20. Known history of primary immunodeficiency diseases. 21. Known active pulmonary tuberculosis. 22. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare the overall survival (OS) of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC); - To compare the OS of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with PD-L1 positive, unresectable, locally advanced, recurrent or metastatic ESCC.;Secondary Objective: - To compare the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and duration of response (DoR) between two treatment arms in overall population; - To compare the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and duration of response (DoR) between two treatment arms in subjects with PD-L1 positive ESCC. - To compare the safety between the two treatment arms.;Primary end point(s): - OS (Overall survival) in the ITT population; - OS in PD-L1 positive subjects in the ITT population.;Timepoint(s) of evaluation of this end point: Assessments will be performed at timepoints described in the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Key secondary endpoints: -ORR (Objective response rate), PFS (Progression free survival) in the ITT population; -ORR. PFS in PD-L1 positive subjects in the ITT population. - Other secondary endpoints: - DCR (Disease control rate), DoR (Duration of response)in the ITT population; - DCR, DoR in PD-L1 positive subjects in the ITT population.;Timepoint(s) of evaluation of this end point: Assessments will be performed at timepoints described in the protocol. | — |
Countries
Australia, Belgium, China, France, Hungary, Romania, Spain, United States
Contacts
Public ContactWinnie Leung
Innovent Biologics (Suzhou) Co., Ltd.
Outcome results
None listed