Diagnostic Biomarkers for Checkpoint Inhibitor-related Pneumonitis

Prospective Study of NMR-based Serum Metabolic Profiles for the Diagnosis of Checkpoint Inhibitor-related Pneumonitis

Checkpoint inhibitor-related pneumonitis (CIP) is a common fatal immune-related adverse events of PD-1/PD-L1 inhibitors. Early diagnosis of CIP is crucial for timely intervention and improved prognosis; however, the absence of precise and effective diagnostic techniques often leads to underdiagnosis and misdiagnosis. The investigators conducted a prospective clinical study to evaluate the effectiveness of ¹H-nuclear magnetic resonance (NMR)-based lipoprotein and metabolite analysis in diagnosing checkpoint inhibitor-related pneumonitis (CIP), aiming to improve its early diagnosis rate.

Study Overview

• Status: Recruiting
• Conditions: Checkpoint Inhibitor-related Pneumonitis

Detailed Description

Checkpoint inhibitor-related pneumonitis (CIP) is a common and potentially fatal immune-related adverse event associated with PD-1/PD-L1 inhibitor therapy. The early and accurate diagnosis of CIP is crucial for timely intervention and improving patient prognosis. However, in clinical practice, the overlapping clinical presentations and imaging features of CIP with infectious pneumonia, tumor progression, or other pulmonary diseases pose a significant diagnostic challenge. The current lack of precise and specific diagnostic techniques often leads to underdiagnosis or misdiagnosis. This diagnostic dilemma can delay the optimal treatment window and may result in the unnecessary interruption or discontinuation of effective immunotherapy, ultimately compromising overall anti-tumor efficacy.

Metabolomics, the comprehensive analysis of small-molecule metabolites, provides a dynamic readout of an organism's physiological state and has shown great promise in biomarker discovery for various diseases. Serum, in particular, offers an easily accessible biofluid that reflects systemic metabolic alterations. ¹H-Nuclear Magnetic Resonance (¹H-NMR) spectroscopy is a robust, reproducible, and quantitative platform ideal for profiling key serum components, including lipoproteins and a wide range of low-molecular-weight metabolites, in a high-throughput manner. The investigators hypothesize that the development of CIP induces a distinct, detectable alteration in the host's systemic metabolic profile, which can be captured by NMR analysis and serve as a diagnostic signature.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Chengzhi Zhou, MD; Phone Number: 81567329; Email: doctorzcz@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510100
      • Recruiting
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Chengzhi Zhou; Phone Number: 81567329; Email: doctorzcz@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Prospective, dual-cohort, biomarker discovery study

Description

Inclusion Criteria:

1. Patients with a pathological diagnosis of lung cancer;
2. The subject has received at least one course of immune checkpoint inhibitor treatment;

3. Capable of understanding and voluntarily signing an informed consent form.

   For the CIP group, the following additional criteria must be met:

4. Highly suspected of having checkpoint inhibitor pneumonitis based on radiological abnormalities and/or pulmonary symptoms (including fever, cough, and dyspnea).

   For the Control group, the following additional criteria must be met:

5. Has had no clinical symptoms or radiographic evidence suggestive of pneumonitis at enrollment or prior to enrollment.

Exclusion Criteria:

1. Pulmonary lesions were definitively diagnosed as tumor progression, bacterial pneumonia, or pulmonary edema;
2. Incomplete or missing follow-up data.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Experimental group; Checkpoint inhibitor-related pneumonitis
Control group; Lung cancer patients who received immunotherapy but did not develop CIP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance	The Area Under the Receiver Operating Characteristic Curve (AUROC) of a classifier model derived from NMR serum metabolic profiles to distinguish between patients with confirmed checkpoint inhibitor-related pneumonitis and control patients on immunotherapy without pneumonitis.	Blood sampling for testing within 1 day after enrollment.

Collaborators and Investigators

• Sponsor: Zhou Chengzhi

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2026
• Primary Completion (Estimated): January 10, 2027
• Study Completion (Estimated): January 10, 2028

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 5, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Metabolism; Checkpoint inhibitor-related pneumonitis; ¹H-nuclear magnetic resonance
• Other Study ID Numbers: CROC202601

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