A Phase III Trial of Neoadjuvant Sintilimab and Chemotherapy for NSCLC Harboring No Driver Mutations

Neoadjuvant Sintilimab and Platinum-based Chemotherapy for Resectable Locally Advanced NSCLC Harboring no Driver Mutations: A Prospective, Randomized, Multicenter Phase III Trial

This is a randomized, open-label study designed to evaluate the safety and efficacy of neoadjuvant PD-1 antibody plus chemotherapy followed by surgery in resectable stage IIIA non-small cell lung cancer.

The primary endpoint: pCR rate The second endpoint: MPR, DFS, MRD

Study Overview

• Status: Recruiting
• Conditions: NSCLC, Stage IIIA; EGF-R Negative Non-Small Cell Lung Cancer; ALK Negative NSCLC
• Intervention / Treatment: Drug: PD-1 and chemotherapy

Detailed Description

This study is a prospective, multicenter, phase III randomized controlled clinical study. Stage IIIA NSCLC patients with EGFR mutation negative and ALK rearrangement negative were enrolled, and after 2 courses of treatment with Sintilimab combined with Platinum-based Chemotherapy, they were randomly assigned 1:1 to the control group (surgical resection and postoperative treatment for 2 courses are recommended) or the experimental group (surgery after 2 courses of treatment).

The primary endpoint is pCR rate. The second endpoints are MPR, DFS, and MRD.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jiang Fan, MD; Phone Number: 15901013210; Email: fan_jiang@tongji.edu.cn
• Study Contact Backup: Name: Dong Lin, MD; Phone Number: 18121299433; Email: dlin2014@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital
      • Principal Investigator: Jiang Fan, MD
      • Contact: Jiang Fan, MD; Phone Number: 02163240090; Email: fan_jiang@tongji.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Resectable stage IIIA NSCLC, EGFR mutation-negative and ALK rearrangement negative (8th UICC TNM staging);
2. No prior anti-tumor therapy for NSCLC;
3. Age from 18 to 75 years old;

4. Adequate organ function:

   Hemoglobin ≥9.0g/L; White blood cell count 4.0~10×109/L; The absolute value of neutrophils (ANC) ≥ 1.5×109/L; Platelet count ≥100×109/L; Total bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST≤2.5 times the upper limit of normal; The international normalized ratio of prothrombin time is ≤1.5 times the upper limit of normal value, and the partial thromboplastin time is within the range of normal value; Creatinine ≤ 1.5 times the upper limit of normal;

5. No chemotherapy, radiotherapy or hormone therapy for malignant tumors, no history of other malignant tumors, excluding patients who have received hormone therapy for prostate cancer and have had DFS for more than 5 years;
6. ECOG 0～1;

Exclusion Criteria:

1. Double primary or multiple primary NSCLC;
2. EGFR mutation or ALK mutation was positive
3. patients with psychosis;
4. Pre-existing or coexisting bleeding disorders;
5. Other uncontrollable and inoperable patients;
6. Patients whose previous operations have prevented this operation from being performed;
7. Female patients who are pregnant or breastfeeding;
8. For patients who are allergic to the drugs in the program.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Neoadjuvant therapy of Sintilimab and chemotherapy in 2 cycles before surgery and optional adjuvant therapy of Sintilimab and chemotherapy in 2 cycles after surgery	Drug: PD-1 and chemotherapy; Sintilimab+(Squamous)ABX+DDP/CBP, or (non-Squamous)PEM+DDP/CBP
Experimental: Experimental group; Neoadjuvant therapy of Sintilimab and chemotherapy in 4 cycles before surgery	Drug: PD-1 and chemotherapy; Sintilimab+(Squamous)ABX+DDP/CBP, or (non-Squamous)PEM+DDP/CBP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologically complete response (pCR) rate	in three weeks after the surgical resection

Secondary Outcome Measures

Outcome Measure	Time Frame
Major pathological response (MPR) rate	in three weeks after the surgical resection
Disease-free survival (DFS)	one, two, three and five years since the initial treatment (each treatment is 2 days)
Minimal residual disease(MRD)	in one week before each cycle and in the forth week after the surgical resection (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Tongji University
• Investigators: Principal Investigator: Jiang Fan, MD, Shanghai General Hospital; Shanghai Pulmonary Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2021
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): October 31, 2025

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 7, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Phase III; PD-1; Locally Advanced; Neoadjuvant; Platinum-based
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: SGHDOT 21-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No