SHR-1210 in Combination With Apatinib and Chemotherapy in Patients With Advanced Esophageal Squamous Cell Cancer

Study Overview
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Brief Summary
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Patients with previously untreated advanced or metastatic esophageal squamous cell carcinoma are recruited to this prospective non-randomized study comprising two separate cohorts. Patients will receive SHR-1210, a novel anti-PD-1 antibody, with apatinib and either irinotecan or paclitaxel liposome plus nedaplatin. The primary endpoint is to determine the objective response rate (ORR) of patients in both cohorts. The regimen(s) of promising efficacy will be further verified in subsequent randomized studies to define the optimal combination of immunotherapy, anti-angiogenesis and chemotherapy in advanced esophageal cancer patients.

Official Title
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SHR-1210, a Novel Anti-PD-1 Antibody, in Combination With Apatinib and Irinotecan/Paclitaxel Liposome Plus Nedaplatin in Patients With Previously Untreated Advanced or Metastatic Esophageal Squamous Cell Cancer: a Phase II Study

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: SHR-1210
* Drug: Apatinib
* Drug: Irinotecan Injection
* Drug: Paclitaxel liposome
* Drug: Nedaplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma of the esophagus, locally advanced, unresectable, recurrent or metastatic disease. Have not received prior systemic therapy. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1. Life expectancy >12 weeks. Adequate organ function. For females of child bearing potential, a negative urine or serum pregnancy test result within 72h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study until 2 months after the last dose of any of the drugs in the study. Willing and able to provide written informed consent and comply with the requirements of the study. Exclusion Criteria: Any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix within 5 years prior to study entry. Known central nervous system (CNS) metastases. Prior therapy with any of the immune check-point inhibitors. Known immediate or delayed hypersensitivity reaction to SHR-1210, apatinib, irinotecan, paclitaxel liposome, nedaplatin or their excipients. Subjects with any active autoimmune disease or history of autoimmune disease. Known Human Immunodeficiency Virus (HIV) infection, active Hepatitis B or Hepatitis C infection. Concurrent medical condition requiring the use of cortisol (>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids no more than 10 mg/day prednisone or equivalent. Received a live vaccine within 4 weeks of the first dose of study medication. Hypertension with a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg that is not effectively controlled by anti-hypertensive therapy. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) > NYHA II congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention. Unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs. Active digestive ulcer disease, inflammatory bowel disease, intestinal obstruction or any other condition that, in the clinical judgment of the Principal Investigator, may cause severe gastrointestinal bleeding or perforation. Active infection or an unexplained fever > 38.5°C before 4 weeks of enrollment. Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic conditions. Pregnant or lactating female. Familial, sociological or geographical conditions that, in the clinical judgment of the Principal Investigator, do not permit compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients with advanced or metastatic esophageal squamous cell carcinoma are to receive SHR-1210 with apatinib and irinotecan injection in cohort 1. | Drug: SHR-1210<br>* a novel anti-PD-1 antibody<br>Drug: Apatinib<br>* a VEGFR-2 tyrosine kinase inhibitor<br>Drug: Irinotecan Injection<br>* cytotoxic agent that binds to topoisomerase I<br>|
| Experimental: Cohort 2<br>Patients with advanced or metastatic esophageal squamous cell carcinoma are to receive SHR-1210 with apatinib and paclitaxel liposome plus nedaplatin in cohort 2. | Drug: SHR-1210<br>* a novel anti-PD-1 antibody<br>Drug: Apatinib<br>* a VEGFR-2 tyrosine kinase inhibitor<br>Drug: Paclitaxel liposome<br>* cytotoxic agent that prevent depolymerization of cellular microtubules<br>Drug: Nedaplatin<br>* cytotoxic agent that cross-links and denatures strands of DNA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | objective response rate of the patients in cohort 1 and cohort 2 | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | progression-free survival (PFS) of the patients in cohort 1 and cohort 2 | 24 months | 
| overall survival | overall survival of the patients in cohort 1 and cohort 2 | 24 months | 
| treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 24 months |