Sintilimab Combined With Anlotinib for Perioperative Non-small Cell Lung Cancer Based on MRD Evaluation

Study Overview
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Brief Summary
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To study the efficacy of sintilimab combined with anlotinib for perioperative non-small cell lung cancer. To explore the clearance effect of sintilimab combined with anlotinib for postoperative adjuvant therapy based on evaluating minimal residual disease.

Detailed Description
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Patients with resectable non-small cell lung cancer (NSCLC) have a high postoperative recurrence rate. Perioperative treatment, which can improve the resection rate and clear the minimal residual disease, is the main mean of preventing recurrence, including preoperative neoadjuvant and postoperative adjuvant therapies. In recent years, immunotherapy can significantly improve the pathological remission rate and prolong the survival as a perioperative treatment. In addition to single-agent or combined chemotherapy, the exploration of immunotherapy with other therapeutic strategies is still lacking. In 2018, we originally designed sintilimab combined with anlotinib in the first-line treatment of advanced NSCLC. This clinical study plans to: ① apply the de-chemotherapy model to the perioperative phase of early NSCLC, ② explore sintilimab combined with anlotinib in preoperative neoadjuvant and postoperative adjuvant therapies, ③ explore clearance effect of sintilimab combined with anlotinib for postoperative adjuvant therapy based on evaluating minimal residual disease (MRD), in order to improve the efficacy of perioperative NSCLC and prolong survival.

Official Title
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Sintilimab Combined With Anlotinib for Perioperative Non-small Cell Lung Cancer Based on MRD Evaluation: a Clinical Study

Conditions
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Non-small Cell Lung Cancer, Minimal Residual Disease, Immunotherapy, Anti-angiogenesis

Intervention / Treatment
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* Drug: sintilimab combined with anlotinib
* Drug: sintilimab monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cyologically confirmed stage II-IIIa NSCLC patients; NSCLC patients with negative driver gene: EGFR wild-type, no ALK fusion mutation, no ROS1 fusion mutation; ECOG PS: 0 1; Pulmonary function index meets the surgical criteria; No previous systemic anti-tumor treatment. Exclusion Criteria: Patients with central cavitary squamous cell carcinoma or investigator-assessed bleeding symptoms or bleeding tendency were excluded.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination therapy group<br>Sintilimab combined with anlotinib | Drug: sintilimab combined with anlotinib<br>* Sintilimab (200mg/time, every 3 weeks) combined with anlotinib (12mg, once daily on day 1 to 14 per cycle) for 2 cycles (42 days). Radical surgery is performed within 4 - 6 weeks treatment. Sintilimab combined with anlotinib therapy repeats every 3 weeks until one year after surgery.<br>* Other names: immunotherapy combined with antiangiogenic therapy;|
| Experimental: Single-agent therapy group<br>Sintilimab monotherapy | Drug: sintilimab monotherapy<br>* Sintilimab (200mg/time, every 3 weeks) combined with anlotinib (12mg, once daily on day 1 to 14 per cycle) for 2 cycles (42 days). Radical surgery is performed within 4 - 6 weeks treatment. Sintilimab monotherapy repeats every 3 weeks until one year after surgery.<br>* Other names: immunotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathologic response (MPR) | Residual tumor cells of the surgical specimens were ≤10% based on pathological evaluation. | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete pathologic response (CPR) | Residual tumor cells of the surgical specimens were 0% based on pathological evaluation. | 2 months | 
| Event free survival (EFS) | Time from randomization to any of the following: disease progression; new primary NSCLC; death from any cause | 16 months | 
| Overall survival (OS) | Radiographic assessments were performed when enrolled and every 8 weeks until disease progression after chemotherapy according to RECIST version 1.1. After PD, collect the survival information every 16 weeks until death or withdrawal of study consent. | 32 months |