Preoperative Sintilimab Combined With Bevacizumab and Chemotherapy for Resectable Non-Small Cell Lung Cancer

The Safety and Feasibility of Preoperative Sintilimab Combined With Bevacizumab and Chemotherapy for Locally Advanced Resectable Non-Small Cell Lung Cancer

Neoadjuvant chemotherapy followed by surgery has been recommended as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. Drugs targeting PD-1/PD-L1 pathway have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents targeting VEGF (bevacizumab) has also been used for the first line treatment of advanced or metastatic NSCLC. Therefore, we conduct this single-arm clinical trial, which aims to investigate the safety and feasibility of neoadjuvant sintilimab combined with bevacizumab and chemotherapy followed by surgery in treating locally advanced and resectable NSCLC.

Study Overview

• Status: Recruiting
• Conditions: Lung Neoplasm Malignant
• Intervention / Treatment: Drug: sintilimab; Drug: bevacizumab

Detailed Description

Lung cancer is one of the most common malignancies around the world. Neoadjuvant chemotherapy followed by surgery has been recommended as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. Bevacizumab targeting VEGF is a widely used antitumor drugs in different types of malignancies, including late-stage NSCLC. Immune checkpoint inhibitor (ICI) targeting PD-1 has also been confirmed to be effective in NSCLC patients. Therefore, we conduct this prospective single-arm clinical trial, to investigate the safety and feasibility of neoadjuvant sintilimab (ICI targeting PD-1) combined with bevacizumab and chemotherapy followed by surgery in treating locally advanced and resectable NSCLC. Twenty patients with stage II-IIIA NSCLC will be enrolled. And the primary endpoint of this study is the safety of this newly developed neoadjuvant treatment. The secondary endpoints are feasibility, radiological response and rate of major pathological response.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hecheng Li, MD, PhD; Phone Number: 0086-021-64370045; Email: lihecheng2000@hotmail.com
• Study Contact Backup: Name: Yuyan Zheng, MD; Phone Number: 0086-15280093677; Email: yuyanzheng@outlook.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Yuyan Zheng, MD; Phone Number: 0086-15280093677; Email: yuyanzheng@outlook.com
      • Contact: Hecheng Li, MD,PHD; Phone Number: 0086-021-64370045; Email: lihecheng2000@hotmail.com
      • Principal Investigator: Hecheng Li, MD,PHD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed, previously untreated and surgically resectable non-small cell lung cancer (stage II-IIIA, patients with squamous cell carcinoma or EGFR mutation should not be included);
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
3. Satisfactory preoperative laboratory testing and adequate pulmonary function for surgery;
4. Patients approve and sign the informed consent.

Exclusion Criteria:

1. Pancoast tumor, squamous cell carcinoma, large-cell carcinoma and sarcomatoid carcinoma;
2. Patients with active autoimmune disease or history of autoimmune disease;
3. Patients who have a condition requiring systemic treatment with either prednisone or other immunosuppressive medications;
4. Patients with a history of symptomatic interstitial lung disease;
5. History of allergy to study drug components;
6. Women must not be pregnant or breast-feeding;
7. Men with female partners that are not willing to use contraception;
8. Patients who have received prior chemotherapy, anti-angiogenesis therapy and immunotherapy for this malignancy or for any other past malignancy;
9. Patients who have received prior treatment for non-small cell lung cancer;
10. Any mental or psychological condition which would not permit the patient to complete the study or understand the patient information;
11. Patients who have major hemoptysis within the past 4 weeks, tumor has invasion or is close to great vessels;
12. Patients with high risk of major bleeding;
13. Patients who have arterial thrombotic events, esophageal varices, peptic ulcers, wounds or bone fractures;
14. Patients who have prior malignancies;
15. HIV, HBV, HCV infection or active pulmonary tuberculosis;
16. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant treatment; Participants will receive 4 doses of sintilimab (200 mg, IV) and bevacizumab (15 mg/kg, IV) every 3 weeks (Q3W). Participants will also receive 4 doses of carboplatin (AUC=5, IV) and pemetrexed (500 mg/m2, IV) Q3W. Surgery will be performed within 4 to 6 weeks after completion of preoperative therapy. After the second dose of sintilimab, bevacizumab and chemotherapy, contrast-enhanced chest CT will be performed. Patients with progression disease will receive surgery without the last 2 doses of treatment.

Drug: sintilimab; Sintilimab 200 mg, 4 cycles of treatment before surgery; Other Names: IBI308; Xindili Dankang; Drug: bevacizumab; bevacizumab 15 mg/kg, 4 cycles of treatment before surgery; Other Names: Bei Fa Zhu Dankang Zhusheye

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Rate of grade 3 and higher grade treatment-related adverse events)	Adverse events will be evaluated and recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).	From date of treatment allocation until surgery or up to at least 90 days after last dose of preoperative treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response Rate	Major pathologic response is predefined as no more than 10% of residual viable tumor cells in primary lesions.	Two weeks after surgery
Radiographic Response	Radiographic response will be evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.	From date of treatment allocation and during treatment period up to 4 months
Feasibility (Completion rate of neoadjuvant treatment and surgery)	Propotion of participants who complete neoadjuvant treatment and receive surgery within 42 days after preoperative therapies.	From date of treatment allocation until surgery, assessed up to 5 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Hecheng Li, MD, PhD, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 16, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Non-small cell lung cancer; Neoadjuvant therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: RTS-014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No