Efficacy and Safety of First-line Anti-PD-1/PD-L1 Monoclonal Antibody in Combination With Chemotherapy and Bronchoscopy-assisted Interventional Therapy in Patients With Advanced Central Non-small Cell Lung Cancer

NCT04702009 | Completed Phase 2

• 1 other identifier: 2021HY017
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Lung cancer is one of the malignant tumors with high morbidity and mortality. Several PD-1/PD-L1 immune checkpoint inhibitors have been approved for the treatment of advanced non-small cell lung cancer (NSCLC). However, its overall effective population is only 20%, and even in studies of enriched populations (such as PD-L1 ≥ 50%), its single-drug effective rate is only about 40%. Therefore, this study aims to explore the efficacy and safety of anti-PD-1/PD-L1 monoclonal antibodies and chemotherapy in combination with bronchoscopy-assisted lnterventional therapy in the first-line treatment of advanced central non-small cell lung cancer. We conducted a randomized controlled, prospective clinical trial to examine the efficacy, safety, and mechanism of anti-PD-1/PD-L1 monoclonal antibodies, chemotherapy, in combination with bronchoscopy-assisted interventional therapy vs anti-PD-1/PD-L1 monoclonal antibody in combination with chemotherapy as the first-line treatment of patients with advanced central NSCLC.

Conditions

Advanced Lung Carcinoma; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• progression free survival (PFS)

  To evaluate the progression free survival (PFS) in the first-line treatment of patients with advanced central NSCLC

  1 year

Secondary Outcomes (5)

• objective response rate (ORR)

  6 weeks

• disease control rate (DCR)

  6 weeks

• overall survival (OS)

  2 years

• Number of participants with treatment-related adverse events (AE) as assessed by CTCAE v5.0

  2 years

• quality of life (QoL)

  2 years

Study Arms (2)

CIT alone

ACTIVE COMPARATOR

Participants randomized to CIT alone received standard first-line chemoimmunotherapy (CIT) per protocol (see Intervention description).

Drug: Chemoimmunotherapy (CIT): Sintilimab + Platinum-Based Doublet Chemotherapy

BIT + CIT

EXPERIMENTAL

Participants randomized to BIT+CIT underwent bronchoscopic intervention therapy (BIT) within 14 days after randomization (either 1 session before CIT initiation or 2 sessions: before CIT and before Cycle 3), followed by first-line CIT. BIT consisted of therapeutic flexible bronchoscopy with endobronchial tumor debulking using high-frequency electrocautery; airway stent could be placed if clinically indicated. CIT was administered per protocol (see Intervention description).

Drug: Chemoimmunotherapy (CIT): Sintilimab + Platinum-Based Doublet Chemotherapy; Procedure: Chemoimmunotherapy (CIT): Sintilimab + Platinum-Based Doublet Chemotherapy

Interventions

Chemoimmunotherapy (CIT): Sintilimab + Platinum-Based Doublet Chemotherapy DRUG

CIT (chemoimmunotherapy): anti-PD-1 sintilimab (Tyvyt) 200 mg IV on Day 1 q3w combined with platinum-based doublet chemotherapy at standard label doses selected by histology (squamous: gemcitabine + cisplatin/carboplatin or taxane + carboplatin; nonsquamous: pemetrexed + cisplatin/carboplatin). Treatment q3w for 4-6 cycles, then maintenance sintilimab ± pemetrexed until progression, unacceptable toxicity, consent withdrawal, or investigator decision. Dose modifications per labels/protocols; irAEs managed per guidelines (hold sintilimab, corticosteroids as indicated).

BIT + CIT; CIT alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Patients volunteer to participate in clinical studies and sign an informed consent (ICF), and are willing to follow and able to complete all trial procedures.
• )18-75 years of age 3) All patients included are diagnosed with lung cancer detected by fibrous bronchoscope or percutaneous lung puncture biopsy, and are confirmed as NSCLC by Immunohistochemistry.
• \) Obstruction-type central lung cancer that cannot be surgically removed. 5) Patients without EGFR, ALK, and ROS mutation. 6) Patients have not previously received systemic treatment for phase IV NSCLC or patients receiving the adjuvant or neoadjuvant therapy for more than 6 months before the diagnosis of phase IV NSCLC.
• \) Within 4 weeks, at least one measurable lesions are required for researchers to evaluate in accordance with RECIST 1.1 requirements.
• \) Appropriate tumor tissues for PD-L1 expression level determination are required.
• \) Relevant laboratory tests indicate tolerance for chemotherapy, immunotherapy, and bronchoscopy.

You may not qualify if:

• Patients with uncertain diagnosis.
• Non-central NSCLC patients.
• Patients with contraindications to chemotherapy or immunotherapy.
• Bronchoscopy is contraindicated in patients.
• Patients have other active malignancies. Patients with cured limited tumors, such as skin substrate cell carcinoma, skin squamous cancer, superficial bladder cancer, carcinoma in situ of prostate, carcinoma in situ of cervix, and breast in-place cancer, can be included.
• Patients with human immunodeficiency virus (HIV) infection.
• Patients with infection of active tuberculosis.
• Patients have received a live vaccines within 28 days of the first drug use. Patients receiving inactivated viral vaccines to treat seasonal influenza are allowed, but inactivated live influenza vaccines with intracn nasal drugs are not allowed.
• Pregnant or lactating women.
• Patients have a known history of psychosophedic substance abuse or drug abuse;
• The researchers determined that there may be other factors that might have contributed to the early termination of the study.

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai pulmonary hospital, Tongji University

Shanghai, Shanghai Municipality, 200433, China

Location

Related Publications (6)

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.

  PMID: 31912902 BACKGROUND

• He Y, Rozeboom L, Rivard CJ, Ellison K, Dziadziuszko R, Yu H, Zhou C, Hirsch FR. MHC class II expression in lung cancer. Lung Cancer. 2017 Oct;112:75-80. doi: 10.1016/j.lungcan.2017.07.030. Epub 2017 Jul 29.

  PMID: 29191604 BACKGROUND

• He Y, Rozeboom L, Rivard CJ, Ellison K, Dziadziuszko R, Yu H, Zhou C, Hirsch FR. PD-1, PD-L1 Protein Expression in Non-Small Cell Lung Cancer and Their Relationship with Tumor-Infiltrating Lymphocytes. Med Sci Monit. 2017 Mar 9;23:1208-1216. doi: 10.12659/msm.899909.

  PMID: 28275222 BACKGROUND

• Deng J, Zhao S, Zhang X, Jia K, Wang H, Zhou C, He Y. OX40 (CD134) and OX40 ligand, important immune checkpoints in cancer. Onco Targets Ther. 2019 Sep 6;12:7347-7353. doi: 10.2147/OTT.S214211. eCollection 2019.

  PMID: 31564917 BACKGROUND

• He Y, Yu H, Rozeboom L, Rivard CJ, Ellison K, Dziadziuszko R, Suda K, Ren S, Wu C, Hou L, Zhou C, Hirsch FR. LAG-3 Protein Expression in Non-Small Cell Lung Cancer and Its Relationship with PD-1/PD-L1 and Tumor-Infiltrating Lymphocytes. J Thorac Oncol. 2017 May;12(5):814-823. doi: 10.1016/j.jtho.2017.01.019. Epub 2017 Jan 26.

  PMID: 28132868 BACKGROUND

• He Y, Jia K, Dziadziuszko R, Zhao S, Zhang X, Deng J, Wang H, Hirsch FR, Zhou C. Galectin-9 in non-small cell lung cancer. Lung Cancer. 2019 Oct;136:80-85. doi: 10.1016/j.lungcan.2019.08.014. Epub 2019 Aug 16.

  PMID: 31454748 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 8, 2021
• Study Start: January 20, 2021
• Primary Completion: October 17, 2025
• Study Completion: January 20, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months after publication and ending 5 years after publication.
• Access Criteria: Data will be available to researchers who provide a methodologically sound proposal. Requests should be directed to the corresponding author. Access will be subject to institutional review and execution of any required data access agreement.

Locations

CN (1)