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

Not Applicable

Recruiting

• Conditions: Lung Neoplasm Malignant
• Interventions: Drug: sintilimab; Drug: bevacizumab

• Registration Number: NCT04973293
• Lead Sponsor: Ruijin Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-07-13
• Study First Submitted QC: 2021-07-13
• Study First Posted: 2021-07-22
• Study Start: 2022-10-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-16
• Last Update Posted: 2024-11-19
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant treatment	sintilimab	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.
Neoadjuvant treatment	bevacizumab	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China