Neoadjuvant Triprizumab and Radiotherapy in Operable Patients With Stage IIA-IIIA Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Neoadjuvant Triprizumab and Radiotherapy in Operable Patients With Stage IIA-IIIA Non-small Cell Lung Cancer

Official Title
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The Efficacy and Safety of Neoadjuvant Triprizumab and Radiotherapy in Operable Patients With Stage IIB-IIIA Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer, Neoadjuvant Therapy, Radiotherapy, Immunotherapy

Intervention / Treatment
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* Drug: Toripalimab
* Radiation: Conventional segmental radiotherapy
* Other: opreation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must volunteer participating in clinical trial; patients fully understand and sign the Informed Consent Form (ICF) 18   70 years old, gender not limited Histologically confirmed resectable stage IIA-IIIA NSCLC without prior treatment Patients must have at least one target lesion to be used to assess response on this protocol as defined by RECIST 1.1 Agree to provide PD-L1 immune tissue sections and corresponding pathology reports for biomarker evaluation (Tumor tissue samples must be fresh or archived samples obtained within 3 months before enrollment Have a performance status of 0 or 1 on the ECOG Performance Scale Good organ function: ANC ≥ 1500/μL; PLT ≥ 100000/μL; HB ≥ 10.0g/dL; CR ≤ 1.5 × ULN or CrCl ≥ 60 mL/min (Use Cock-Gault formula); TB ≤ 1.5 × ULN (For patients with total bilirubin levels > 1.5 × ULN, direct bilirubin is within normal limits); AST and ALT ≤ 2.5 × ULN; TSH is within normal limits. Note: If TSH is not within the normal range at baseline, if T3 and free T4 are within the normal range, then the patient can still meet the inclusion criteria. IN、RPT、APTT≤1.5×ULN Patients must volunteer and be able to follow research plan visits, treatment plans, laboratory tests, and other research procedures According to the surgeon's assessment, the total lung function can withstand the proposed lung resection Within 3 days before medication，the serum of fertile woman must be tested by hcg，and the result is negative. Fertile women can use high effective method for contraception in the duration of clinical trail and 180 days after last Administration Exclusion Criteria: Locally advanced unresectable or metastatic disease Non-small small lung cancer (NSCLC) involving the upper sulcus，large cell neuroendocrine cancer (LCNEC), sarcomatoid tumor Patients with known EGFR mutations or ALK translocations, non-squamous carcinoma patients need to know the status of EGFR and ALK mutations Early NSCLC with prior systemic anticancer therapy, including experimental drug therapy Have a history of (non-infectious) pneumonia / interstitial lung disease requiring steroid therapy, or currently have pneumonia / interstitial lung disease requiring steroid therapy Known history of active tuberculosis Known to have active infection requiring systemic treatment known or suspected autoimmune diseases or immunodeficiency, except: patients with a history of hypothyroidism who do not require hormone therapy or are receiving physiological dose hormone replacement therapy; patients with stable type 1 diabetes whose blood glucose is controlled Active hepatitis B or C Has a known history of Human Immunodeficiency Virus (HIV) . Received live vaccine treatment within 30 days before drug administration; but inactivated viral vaccine for seasonal influenza is allowed Peripheral neuropathy ≥ grade 2 Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Overly sensitive reaction to other monoclonal antibodies Have a history of severe allergies to pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin or their preventive medicine Known to have serious or uncontrolled underlying disease According to the investigator's judgment, the patient has a history or current evidence of any disease, treatment or laboratory abnormality that may confuse the test results, interfere with the participant's participation in the full trial, or not in the best interest of the participant to participate in the trial

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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Accepts Healthy Volunteers

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: Toripalimab<br> | Drug: Toripalimab<br>* 200 mg Toripalimab intravenously every 3 weeks 3 doses of Toripalimab before operation 14 doses of Toripalimab 30 days after operation<br>* Other names: JS001;Radiation: Conventional segmental radiotherapy<br>* the does of radiation will be 40-45Gy. The day of the first dose of Toripalimab and the first day of radiation must be the same day.<br>Other: opreation<br>* The operable patients will accept radical operated in 28-42 days after the third dose of Toripalimab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic response rates | Major pathological response rates assessed by independent center pathology | 42months | 
| Event-free survival | The time from the beginning of enrollment to the occurrence of any events, including death, disease progression, change of chemotherapy regimen, change of chemotherapy, addition of other treatments, the occurrence of fatal or intolerant side effects and other events | 42months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Kaplan-Meier median estimates and curves will be used to describe OS survival functions | 42 months | 
| Pathologic complete response (pCR) rates | Pathologic complete response (pCR) rate is defined as the number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review. | 42months | 
| Disease-free survival | Some time until the tumor recurs or die for various reasons | 42 months | 
| Number of Participants Experiencing Adverse Events (AEs) and serious adverse events (SAEs) | Adverse events are defined as any adverse medical events that occur in the participants taking the drugs and do not necessarily have a causal relationship with the treatment. AEs/SAEs were evaluated using NCI-CTCAE v5.0 | 42 months |