Perioperative Immunotherpay Versus Adjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
For resectable non-small cell lung cancer, neoadjuvant immunochemotherapy plus adjuvant immunotherapy or adjuvant immunochemotherapy is usually used in clinical practice. However, it is unclear whether therapeutic strategy is superior. This trial aims to compare the efficacy and safety of these two strategies.

Official Title
-----------------
Perioperative Immunotherpay Versus Adjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer

Conditions
-----------------
Stage II-IIIB(N2) Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: TQB2450
* Drug: Carboplatin
* Drug: Pemetrexed
* Drug: Nab-paclitaxel
* Procedure: Surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient shall sign the Informed Consent Form. Aged 18 ≥ years. Histological or cytological diagnosis of NSCLC by needle biopsy, and stage II-IIIB (N2) confirmed by imageological examinations (CT, PET-CT or EBUS). Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. Life expectancy is at least 12 weeks. At least 1 measurable lesion according to RECIST 1.1. Patients with good function of other main organs (liver, kidney, blood system, etc.) Patients with lung function can tolerate surgery; Without systematic metastasis (including M1a, M1b and M1c); Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of immunotherapy (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative. Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of immunotherapy (whichever is later). Exclusion Criteria: Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment; Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases; With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment; Participants who are allergic to the test drug or any auxiliary materials; Participants with Interstitial lung disease currently; Participants with active hepatitis B, hepatitis C or HIV; Pregnant or lactating women; Participants suffering from nervous system diseases or mental diseases that cannot cooperate; Participated in another therapeutic clinical study; Other factors that researchers think it is not suitable for enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perioperative immunotherapy<br>In this arm, patients will receive neoadjuvant immunochemotherapy and adjuvant immunotherapy. | Drug: TQB2450<br>* Specified dose on specified days<br>Drug: Carboplatin<br>* Specified dose on specified days<br>Drug: Pemetrexed<br>* Specified dose on specified days<br>Drug: Nab-paclitaxel<br>* Specified dose on specified days<br>Procedure: Surgery<br>* Surgery for II-IIIB (N2) non-small cell lung cancer<br>|
| Experimental: Adjuvant immunotherapy<br>In this arm, patients will receive adjuvant immunochemothrapy and immunotherapy | Drug: TQB2450<br>* Specified dose on specified days<br>Drug: Carboplatin<br>* Specified dose on specified days<br>Drug: Pemetrexed<br>* Specified dose on specified days<br>Drug: Nab-paclitaxel<br>* Specified dose on specified days<br>Procedure: Surgery<br>* Surgery for II-IIIB (N2) non-small cell lung cancer<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year event-free survival (EFS) rate | Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | It refers to the proportion of patients who have had a complete response or partial response (according to RECIST1.1) as confirmed by CT evaluation after 3 weeks in all patients who have completed the neoadjuvant therapy. Only patients with measurable lesions at baseline will be analyzed. | Up to 6 months | 
| Pathological complete response (pCR) | pCR is defined as the proportion of participants who have achieved complete pathologic response (on routine hematoxylin and eosin staining, tumors with no viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery. | Up to 8 months | 
| Major pathologic response (MPR) | MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery. | Up to 8 months | 
| Event-free survival (EFS) | Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 72 months | 
| Overall survival (OS) | It is defined as the time (months) from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date. | Up to 72 months | 
| 5-year event-free survival (EFS) rate | Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 72 months | 
| 5-year overall survival (OS) | OS is defined as the time (months) from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date. | Up to 72 months | 
| Adverse event rate | It is defined as the frequency of severe adverse events from the participants enrolling to 30 days after the last drug administration or 30 days after surgery or new anti-cancer therapy, which comes first. | Up to 36 months | 
| Health related quality of life (HRQol) | The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-C30 & LC13, Version 3). EORTC's QLQ-C30 & LC13 (V3.0) is a core scale for lung cancer patients, with a total of 43 items. Among them, Item 29 and 30 are divided into seven grades, which are assigned with 1 to 7 scores according to the answer options. The other items are divided into 4 grades: Not at All, A Little, Quite a Bit, and Very Much, assigned with 1 to 4 scores respectively. The higher score, the worse quality. | Up to 36 months |