CT-Guided Adaptive Radiation Therapy Combine With Anti-PD-1 Antibody Adjuvant Immunotherapy for Thoracic Cancer Patients

Study Overview
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Brief Summary
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This phase II study is to evaluate the safety and efficacy of CT-based adaptive radiation therapy followed by adjuvant anti-PD-1 antibody immunotherapy in treating patients with different types and stages of thoracic malignancies. (CARTAI)

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the safety and toxicity of anti-programmed cell death 1 (PD-1) inhibition consolidation therapy after radiation therapy for multiple thoracic malignancies. SECONDARY OBJECTIVES: I. To assess the efficacy of adjuvant anti-PD-1 antibody immunotherapy after radiotherapy. II. To understand the dynamics and interactions of IDO with others immune pathway biomarkers. III. To evaluate whether IDO immune status could predict the treatment outcomes of radiation and immune combined therapy.

Official Title
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A Safety and Efficacy Study of CT-Guided Adaptive Radiation Therapy With Anti-PD-1 Antibody Adjuvant Immunotherapy in Patients With Thoracic Cancer (CARTAI)

Conditions
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Thoracic Malignancies

Intervention / Treatment
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* Drug: IBI308


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed inform consent form Age >= 18 years and <= 75 years Histologically or cytologically confirmed advanced/metastatic thoracic malignancies Patients must receive adaptive radiation therapy within 45 days before the first dose of trial treatment Eastern Cooperative Oncology Group performance status of 0 or 1 Life expectancy >= 8 weeks Adequate hematologic and end organ function Exclusion Criteria: Prior exposure to any immune checkpoint inhibitors including but not limited to anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies. Prior exposure to any other thoracic radiation therapy before this time radiation therapy. Prior exposure to steroid therapy or any other form of immunosuppressive therapy within 14 days before the first dose of trial treatment No active second cancers Active or prior autoimmune disease or immunodeficiency. Active infections including but not limited to hepatitis B, C ,and HIV. Significant cardiovascular disease Active or untreated central nervous system (CNS) metastases Any unresolved toxicity CTCAE >= Grade 3 from the prior radiation therapy. Known hypersensitivity to humanized antibodies or fusion proteins or any of study drug excipients. Known psychiatric or physical impairments that would interfere with cooperation with the protocol of this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-PD-1 antibody<br>IBI308 200mg intravenous drip every three weeks following adaptive radiation therapy. | Drug: IBI308<br>* A humanized anti-PD-1 monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs and SAEs at 6 months | Number of participants with adverse events and serious adverse events at 6 months will be measured. [CTCAE v4.03] | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate is the percentage of patients with at least once occurrence of PR or CR [RECIST v1.1] | Estimated to be up to 3 years | 
| DoR | Duration of response is the time interval from first occurrence of PR or CR until PD or death [RECIST v1.1] | Estimated to be up to 3 years | 
| AEs | Number of patients with acute and chronic adverse events will be measured [CTCAE v4.03] | Estimated to be up to 3 years | 
| PFS | Progression-Free-Survival is the time interval from the start of treatment until disease progression or death by any cause [RECIST v1.1] | Estimated to be up to 3 years | 
| OS | Overall Survival is the time interval from the start of treatment to death from any cause. | Estimated to be up to 3 years |