Randomized Trial of Glutathione With Anti-PD-1 and Chemotherapy in Advanced NSCLC

Prospective, Randomized Controlled Clinical Trial of Glutathione Combined With PD-1 Antibody and Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer

Chemotherapeutic agents exert significant immunomodulatory effects by influencing tumor-infiltrating immune cells. However, the sequence and combination of chemotherapy regimens differentially modulate immune cell dynamics, ultimately impacting treatment efficacy and patient survival. Glutathione, a critical bioactive molecule, demonstrates broad potential in tumor immunotherapy. Through mechanisms such as scavenging free radicals, modulating immune cell proliferation and differentiation, and regulating cytokine expression, glutathione achieves precise modulation of immune responses to enhance immune system functionality. To investigate whether glutathione can enhance the clinical efficacy of current chemo-immunotherapy regimens in non-small cell lung cancer (NSCLC), investigators conducted this clinical study.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; Chemotherapy; Glutathione; PD1 Antibody
• Intervention / Treatment: Drug: Chemotherapy; Drug: PD1 Inhibitor; Drug: Glutathione

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yi Zhang; Phone Number: +86 15138928971; Email: yizhang@zzu.edu.cn

Study Locations

• China
  • Henan
    • ZhengZhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of lung squamous cell carcinoma or adenocarcinoma.
2. Documented disease progression following first-line chemotherapy or chemo-immunotherapy.
3. Age ≥18 years at the time of enrollment.

Exclusion Criteria:

1. Patients with small cell lung cancer or other histological subtypes of lung cancer.
2. Patients lost to follow-up, who discontinued treatment, or died within one year of diagnosis.
3. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: PD-1 inhibitor plus chemotherapy arm	Drug: Chemotherapy; Platinum-based doublet chemotherapy; Drug: PD1 Inhibitor; e.g. pembrolizumab, camrelizumab, sintilimab, tislelizumab, toripalimab
Experimental: Glutathione combined with PD-1 inhibitor plus chemotherapy arm	Drug: Chemotherapy; Platinum-based doublet chemotherapy; Drug: PD1 Inhibitor; e.g. pembrolizumab, camrelizumab, sintilimab, tislelizumab, toripalimab; Drug: Glutathione; Glutathione is administered as an adjunct intervention to the PD-1 inhibitor plus chemotherapy regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)		From randomization until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months."
Overall Response Rate (ORR)	Proportion of patients achieving predefined tumor volume reduction with sustained duration, defined as those attaining a complete response (CR) or partial response (PR).	From the initiation of treatment until 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	the time from randomization (or treatment initiation) to death from any cause, serving as the gold-standard endpoint for evaluating long-term therapeutic efficacy in oncology.	From randomization until death from any cause, assessed up to 60 months.
Improvement in Immune Parameters	assess every 4 weeks via flow cytometry for peripheral CD8+ T-cell proportion and cytokine levels (e.g., IFN-γ, IL-2).	From baseline until 12 weeks post-treatment completion
QLQ-LC43	Quality of Life Questionnaire for Lung Cancer from the European Organization for Research and Treatment of Cancer (EORTC), assessed at baseline, the end of each treatment cycle (every 3 weeks), and at 12 and 24 weeks post-treatment using the Chinese version of the EORTC QLQ-LC43 questionnaire.	From baseline until 24 weeks post-treatment completion

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 20, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 26, 2025

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2024-KY-0017-002

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