Longitudinal Cohort Study of Immune-Related Adverse Events in Solid Tumor Patients Treated With Immune Checkpoint Inhibitors

NCT07357636 | Recruiting DMC

• 1 other identifier: 2023100
• Study Type: observational
• Target: 940
• Locations: 1 country
• Sites: 6

Brief Summary

Immune checkpoint inhibitors (ICIs) have transformed the treatment of solid tumors but are associated with immune-related adverse events (irAEs) that can affect virtually any organ system. While many irAEs are well recognized, neurological, neurocognitive, and psychiatric toxicities remain diagnostically challenging, potentially severe, and poorly understood, with limited predictive biomarkers. This prospective longitudinal observational cohort study enrolls adult patients with solid tumors initiating a new course of ICI therapy. Participants undergo standardized baseline clinical assessments and biospecimen collection prior to ICI initiation, followed by longitudinal follow-up and event-driven sampling. Patients are dynamically assigned to organ-specific irAE cohorts based on the first clinically significant irAE that dictates management. Patients without grade ≥2 irAEs during follow-up serve as a comparator control cohort. The primary objective is to characterize longitudinal immune and inflammatory biomarker trajectories associated with the development of irAEs and to identify predictive and prognostic biomarkers, with particular emphasis on neurological, neurocognitive, and psychiatric toxicities. Integrated clinical, imaging, and multi-omics data will be used to elucidate mechanisms of toxicity and inform future risk stratification and personalized management strategies.

Conditions

Solid Tumor; Immune-Related Adverse Events; Immunotherapy Toxicity

Keywords

Immune checkpoint inhibitors; Immunotherapy; Biomarkers; Neurotoxicity; Neuroimmune adverse events; immune related adverse events; PD-1 blocker

Outcome Measures

Primary Outcomes (1)

• Time to Clinical Resolution of Immune-Related Adverse Events (Days)

  Among participants who develop grade ≥2 immune-related adverse events (irAEs), the time from irAE diagnosis and initiation of organ-specific treatment (per institutional guidelines) to achievement of organ-specific clinical resolution will be recorded. Criteria for clinical resolution differ by organ system and are defined according to established consensus guidelines, as specified in the corresponding secondary outcome measures.

  From irAE diagnosis through up to 24 months of follow-up

Secondary Outcomes (15)

• Neuro-Sensory irAE Subgroup: Proportion of Participants with Modified Rankin Scale (mRS) Score ≤2

  12 weeks after irAE diagnosis

• Neuro-Sensory irAE Subgroup:Proportion of Participants with Objective Improvement on Nerve Conduction Studies

  12 weeks after irAE diagnosis

• Psychiatric and Cognitive irAE Subgroup:Proportion of Participants with Patient Health Questionnaire-9 (PHQ-9) Score <10

  8 weeks after initiation of targeted treatment

• Psychiatric and Cognitive irAE Subgroup:Proportion of Participants with ≥0.5 Standard Deviation Improvement on ≥2 Standardized Neuropsychological Tests

  12 weeks after irAE diagnosis

• Gastrointestinal and Hepatic irAE Subgroup: Proportion of Participants with ≤3 Bowel Movements per Day and No Hematochezia

  2 weeks after initiation of immunosuppressive therapy

Study Arms (7)

Neuro-Sensory irAE Cohort

Participants who develop a grade ≥2 neurological, neurocognitive, psychiatric, ocular inflammatory, or peripheral nervous system immune-related adverse event.

Gastrointestinal and Hepatic irAE Cohort

Participants who develop grade ≥2 immune-mediated colitis, hepatitis, pancreatitis, or related gastrointestinal toxicities.

Rheumatology and Musculoskeletal irAE Cohort

Participants who develop grade ≥2 inflammatory arthritis, myositis, polymyalgia rheumatica-like syndromes, or related musculoskeletal toxicities.

Vascular and Renal irAE Cohort

Participants who develop grade ≥2 myocarditis, vasculitis, nephritis, or other vascular or renal immune-mediated toxicities.

Hematologic irAE Cohort

Participants who develop grade ≥2 immune-mediated cytopenias or other hematologic toxicities.

Multi-Organ irAE Cohort

Participants who develop two or more distinct grade ≥2 immune-related adverse events involving different organ systems.

Control Cohort

Participants who do not develop any grade ≥2 immune-related adverse events during the defined follow-up period.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) with histologically confirmed solid malignancies who are initiating a new immune checkpoint inhibitor regimen, either as standard of care or within an approved clinical trial. Participants are enrolled prior to the first immune checkpoint inhibitor dose and followed longitudinally to assess the development of immune-related adverse events and associated immune and inflammatory biomarker changes.

You may qualify if:

• Age ≥18 years
• Histologically confirmed solid malignancy
• Planned initiation of a new immune checkpoint inhibitor regimen (monotherapy or combination) as standard of care or on an approved clinical trial
• Ability to provide informed consent
• Baseline study assessments and biospecimen collection completed prior to first ICI dose
• Life expectancy of at least 6 months as determined by treating oncologist
• Availability of archival tumor tissue or willingness to undergo biopsy if archival tissue is unavailable

You may not qualify if:

• Uncontrolled medical, psychiatric, or social conditions that would interfere with study participation or data interpretation
• Chronic systemic immunosuppression exceeding 10 mg/day prednisone equivalent within 14 days prior to enrollment (excluding inhaled, topical, or physiologic replacement doses)
• Prior solid organ transplantation or allogeneic hematopoietic stem cell transplantation
• Untreated, symptomatic, or progressing brain metastases (treated and stable brain metastases allowed if off systemic steroids for at least 7 days)
• Inability or unwillingness to provide required baseline biospecimens

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: collaborator
• Sun Yat-sen University: collaborator
• Chinese PLA General Hospital: collaborator
• Shantou University Medical College: lead
• Fujian Medical University: collaborator

Study Sites (6)

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 430074, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

Hainan Hospital of Chinese PLA General Hospital

Sanya, China

RECRUITING

Affiliated Cancer Hospital of Shantou University Medical College

Shantou, China

RECRUITING

the First Affiliated Hospital of Shantou University Medical College

Shantou, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

The study will retain a variety of biospecimens, including blood (whole blood, plasma, and serum), cerebrospinal fluid, urine, saliva, stool, gastric fluid, bile, synovial fluid, bronchoalveolar lavage fluid, pleural fluid, peritoneal lavage fluid, small intestinal fluid, colonic fluid, tears, tumor tissue, inflammatory biopsy tissue, matched normal tissue, pathology specimens (including formalin-fixed paraffin-embedded tissue), hair, and tongue coating samples.

MeSH Terms

Conditions

Neurotoxicity Syndromes

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Central Study Contacts

Yifei Ma, MD

CONTACT

8618883852716; myf61872169@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, MD

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: January 22, 2026
• Study Start: January 10, 2019
• Primary Completion (Estimated): September 10, 2029
• Study Completion (Estimated): September 10, 2029
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2026.3 to 2029.1
• Access Criteria: The de-identified IPD and supporting documents will be made available to qualified researchers worldwide upon request. Researchers will have access to the fully de-identified individual participant data listed in the previous section, along with the supporting documents including: the final study protocol, statistical analysis plan, the annotated case report forms. The data dictionary. All data will be anonymized in accordance with the HIPAA Safe Harbor method. Interested researchers must submit a formal research proposal outlining their study objectives, analysis plan, and ethical considerations via email for review by our Data Access Committee. Requestors will be required to sign a Data Use Agreement that legally binds them to use the data only for the approved purpose, maintain data security, and prevent re-identification or redistribution. Data will then be securely transferred via encrypted file sharing or made available through a controlled-access repository

Locations

CN (6)