The Impact of Thymosin α-1 on the Efficacy of Concurrent Chemoradiotherapy Followed by Immunotherpay Consolidation for Locally Advanced NSCLC

Study Overview
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Brief Summary
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This prospective phase II randomized study is to determine the impact of thymosin alpha-1 on the concurrent chemoradiotherpay followed by immunotherapy consolidation in patients with locally advanced NSCLC by assessing the survival outcomes, treatment responses and toxicities.

Detailed Description
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This prospective phase II randomized study is to determine the impact of thymosin alpha-1 on the concurrent chemoradiotherpay followed by immunotherapy consolidation in patients with locally advanced NSCLC by assessing the survival outcomes, treatment responses and toxicities. Patients with locally advanced NSCLC who will receive concurrent radiochemotherapy followed by immunotherapy consolidation will be randomly divided into two groups (concurrent Tα1 treatment group and control group [in which Tα1 will not be used]), and the overall survivals, progression-free survivals (PFS), completion rate of immunotherapy consolidation, toxicities/adverse effects, and peripheral blood immune biomarkers will be compared between these two groups.

Official Title
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A Prospective Phase II Controlled Study to Evaluate the Impact of Thymosin Alpha 1 on the Completion Rate of Consolidation Immunotherapy After Radical Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Hypofractionated radiotherapy
* Drug: induction chemo-immunotherapy
* Drug: concurrent chemotherapy
* Drug: Immunotheapy consolidation
* Drug: Thymosin Alpha1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged ≥18 years old histologically confirmed locally advanced and unresectable NSCLC; no prior radiotherapy or surgery; with the life expectancy over 12 weeks; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; adequate bone marrow and hepatic and renal functions; informed consent Exclusion Criteria: Concurrent enrollment in another clinical trial, unless it is an observational (non-interventional) clinical study; With histologically documented combined small-cell lung carcinoma; Major surgery (excluding vascular access placement) within 4 weeks prior to enrollment in the study; Active or prior documented autoimmune disease within the past 2 years; Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis); History of innate immunodeficiency; History of organ transplant that requires the use of immunosuppressives; A mean heart rate-corrected QT interval (QTc) ≥ 470 ms, calculated using Bazett correction from 3 ECG calculation cycles; Poorly managed health conditions that include but are not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active hemorrhagic diseases, hepatitis C or human immunodeficiency virus (HIV) infection, hepatitis B (positive HBsAg and HBV DNA > 500 IU/ml), and mental disorders/social conditions that may hinder the compliance with the study requirements or the ability to give written informed consent willingly; Active tuberculosis; Receipt of live or attenuated vaccination within 30 days prior to the first dose of the investigational agents; History of another primary malignancy within the past 5 years, excluding adequately treated basal or squamous cell skin cancers or cervical carcinoma in situ; Pregnant/breastfeeding women or males/females of reproductive potential who do not use contraception.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent Tα-1 group<br>In this concurrent Tα-1 group, participants receive concurrent chemoradiotherapy followed by immunotherapy consolidation. During this treatment, thymosin alpha-1 was administered at 4.8mg each time. | Radiation: Hypofractionated radiotherapy<br>* Participants were treated with hypofractionated radiotherapy followed by hypo-boost<br>Drug: induction chemo-immunotherapy<br>* All participants receive two cycles of albumin-bound paclitaxel (260mg/m2) on d1 and cisplatin (25mg/m2) from d1 to d3 in combination with tislelizumab (200mg) on d1.<br>* Other names: tislelizumab;Drug: concurrent chemotherapy<br>* Concurrent chemotherapy consists of weekly albumin-bound paclitaxel (50mg/m2) and cisplatin (25mg/m2).<br>* Other names: cisplatin;Drug: Immunotheapy consolidation<br>* Participants without disease progression, grade ≥3 toxicities, and/or grade ≥2 pneumonitis after CCRT receive tislelizumab 200 mg (Q3W) for up to 12 months.<br>* Other names: tislelizumab;Drug: Thymosin Alpha1<br>* Participants in the Tα1 treatment group will receive Tα1 from the beginning of induction chemo-immunotherapy until the completion of immunotherapy consolidation. In detail, Tα-1 would be administered according to the following three stages: Induction chemo-immunotherapy: Tα-1 will be subcutaneously administered at 4.8 mg on d1 and d3 for each cycle. Concurrent chemoradiotherapy: Tα-1 will be subcutaneously administered at 4.8mg biweekly. Immunotherpay consolidation: Tα-1 will be administered concurrently with tislelizumab at 4.8mg (Q3W) for up to 12 months.<br>* Other names: thymalfasin;|
| Other: Control group<br>In control group, participants receive concurrent chemoradiotherapy followed by immunotherapy consolidation. | Radiation: Hypofractionated radiotherapy<br>* Participants were treated with hypofractionated radiotherapy followed by hypo-boost<br>Drug: induction chemo-immunotherapy<br>* All participants receive two cycles of albumin-bound paclitaxel (260mg/m2) on d1 and cisplatin (25mg/m2) from d1 to d3 in combination with tislelizumab (200mg) on d1.<br>* Other names: tislelizumab;Drug: concurrent chemotherapy<br>* Concurrent chemotherapy consists of weekly albumin-bound paclitaxel (50mg/m2) and cisplatin (25mg/m2).<br>* Other names: cisplatin;Drug: Immunotheapy consolidation<br>* Participants without disease progression, grade ≥3 toxicities, and/or grade ≥2 pneumonitis after CCRT receive tislelizumab 200 mg (Q3W) for up to 12 months.<br>* Other names: tislelizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion rate of immunotherapy | Proportion of participants completing 12 months of consolidation of immutherapy | Calculated from the start of treatment to one year after the last treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2 years | 
| Progression-free survival |  | one year | 
| Incidence of ≥grade 2 pneumonia |  | through study completion, an average of 1 year | 
| Drop-out rate during the I/O consolidation |  | One year | 
| The absolute count of total lymphocyte in peripheral blood | Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy. | Calculated from the start of treatment to one year after the last treatment completion; up to 18 months | 
| The expression of peripheral blood cytokines (including IL2, IL4, IL6, IL10, TNF-α, and IFN-γ) | Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy. | Calculated from the start of treatment to one year after the last treatment completion; up to 18 months | 
| The absolute count of peripheral blood lymphocyte subsets (including CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+, and CD56+ NK cells, PD-1+CD8+ T cells, Tim3+ CD8+ T cells, CD62lowCD4+ T cells, PD-1+CD4+ T cells, and Tim3+CD4+ T cells | Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy. | Calculated from the start of treatment to one year after the last treatment completion; up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, Thymosin alpha-1, concurrent chemoradiotherpay, immunotherapy consolidation