Neoadjuvant and Adjuvant Therapy Studies of Sindilizumab in Resectable Lung Cancer

Study Overview
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Brief Summary
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This study is a multi-regional, randomized, double-blind Phase 3 study to compare the efficacy and safety of sintilimab plus chemotherapy (sintilimab combination) vs placebo plus chemotherapy (placebo combination) before surgery and sintilimab vs placebo after surgery in treatment-naive subjects with resectable Stage IIB (primary tumor > 4 cm) to IIIB (resectable N2 only) non-small cell lung cancer (NSCLC).

Official Title
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A Multi-Regional, Randomized, Double-blind, Phase 3 Study of the Efficacy and Safety of Sintilimab Plus Chemotherapy vs Placebo Plus Chemotherapy Before Surgery and Sintilimab vs Placebo After Surgery for Resectable Non-small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Sintilimab
* Drug: Carboplatin
* Drug: Nab-paclitaxel
* Drug: Cisplatin
* Drug: Pemetrexed
* Drug: Docetaxel
* Drug: Paclitaxel
* Drug: Gemcitabine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must sign the written informed consent form (ICF), and be able to follow the visits and relevant procedures specified in the protocol. Age ≥ 18 years. Cytologically or histologically confirmed primary NSCLC (including adenocarcinoma, squamous cell carcinoma). Subjects with Stage IIB (primary tumor > 4 cm), IIIA or IIIB (resectable N2 only) disease based on the 8th edition of the TNM staging classification for lung cancer issued by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification (AJCC8). Deemed radically resectable with curative intent. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Have not received any prior systemic anti-tumor therapy or local radiotherapy for NSCLC. - Exclusion Criteria: Subjects with confirmed or suspected brain metastases. Currently participating in an interventional clinical study or treatment with another study drug or study device within 4 weeks prior to randomization. Received Chinese herbal medicine, Chinese traditional medicine with anti-tumor indications, or drugs with immunomodulatory effects (including thymosin, interferon, interleukin) within two weeks prior to randomization Received a live attenuated vaccine 4 weeks prior to randomization (or planned to receive a live attenuated vaccine during the study). Requiring long term systemic corticosteroids Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive), known active syphilis. Active hepatitis B. -

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sintilimab<br>Neoadjuvant Treatment period: up to 3 cycles of sintilimab plus platinum-based chemotherapy prior to surgery. adjuvant Treatment period: Subjects will receive sintilimab therapy after surgery until disease recurrence, unacceptable toxicity, receiving new anti-tumor therapy, withdrawal of informed consent (ICF), lost to follow-up or death, or other conditions that require treatment discontinuation (whichever occurs first). The maximum duration of postoperative treatment with either sintilimab or placebo is 1 year. | Drug: Sintilimab<br>* 200 mg D1 IV Q3W<br>Drug: Carboplatin<br>* AUC 5 or 6 mg/ml/min D1 IV Q3W<br>Drug: Nab-paclitaxel<br>* 100 mg/m2 D1, 8, 15 IV Q3W<br>Drug: Cisplatin<br>* 75 mg/m2 D1 IV Q3W<br>Drug: Pemetrexed<br>* 500 mg/m2 D1 IV Q3W<br>Drug: Docetaxel<br>* 60 or 75 mg/m2 D1 IV Q3W<br>Drug: Paclitaxel<br>* 175 or 200 mg/m2 D1 IV Q3W<br>Drug: Gemcitabine<br>* 1000 mg/m2 or 1250 mg/m2 D1, 8 IV Q3W<br>|
| Placebo Comparator: Placebo<br>Neoadjuvant Treatment period: up to 3 cycles of placebo plus platinum-based chemotherapy prior to surgery. adjuvant Treatment period: Subjects will receive placebo therapy after surgery until disease recurrence, unacceptable toxicity, receiving new anti-tumor therapy, withdrawal of informed consent (ICF), lost to follow-up or death, or other conditions that require treatment discontinuation (whichever occurs first). The maximum duration of postoperative treatment with either sintilimab or placebo is 1 year. | Drug: Carboplatin<br>* AUC 5 or 6 mg/ml/min D1 IV Q3W<br>Drug: Nab-paclitaxel<br>* 100 mg/m2 D1, 8, 15 IV Q3W<br>Drug: Cisplatin<br>* 75 mg/m2 D1 IV Q3W<br>Drug: Pemetrexed<br>* 500 mg/m2 D1 IV Q3W<br>Drug: Docetaxel<br>* 60 or 75 mg/m2 D1 IV Q3W<br>Drug: Paclitaxel<br>* 175 or 200 mg/m2 D1 IV Q3W<br>Drug: Gemcitabine<br>* 1000 mg/m2 or 1250 mg/m2 D1, 8 IV Q3W<br>Drug: Placebo<br>* 20 ml D1 IV Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival (EFS) | EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first. | Up to approximately 2 years following the beginning of Post-operative Assessment baseline(up to Study 5.4 years ) | 
| Pathological Complete Response (pCR) Rate | pCR rate is defined as absence of residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy | Up to approximately 6 weeks following completion of neoadjuvant treatment (up to Study 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival (DFS) | DFS is defined as the time from surgery to disease recurrence or death due to any cause. | Up to approximately 2 years following the begining of Post-operative Assessment baseline(up to Study 5.4 years ) | 
| Major Pathological Response (mPR) Rate | mPR rate is defined as ≤ 10% residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy. | Up to approximately 6 weeks following completion of neoadjuvant treatment (up to Study 2 years) | 
| Overall survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 5.4 years | 
| Safety parameters: AEs | The relationship of study drug and the severity of all adverse events (AEs) | Up to approximately 5.4 years | 
| Safety parameters:IRRs | The relationship of study drug and the severity of infusion-related reactions (IRRs). | Up to approximately 5.4 years | 
| Safety parameters: surgery delay rate | The relationship of study drug and the severity of surgery delay rate. | Up to approximately 5.4 years | 
| Immunogenicity-ADA | The positive rate of anti-drug antibody (ADA) | Up to approximately 1.6 years | 
| Immunogenicity-NAb | The positive rate of neutralizing antibody (NAb) | Up to approximately 1.6 years |