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

Shantou University Medical College

Status: Enrolling

Conditions: Immunotherapy Toxicity; Solid Tumor; Immune-Related Adverse Events

Study type: Observational

Funder types: Other

Identifiers

NCT07357636

2023100

Details and patient eligibility

About

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.

Full description

Immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 pathways have demonstrated substantial clinical benefit across multiple solid malignancies. However, their mechanism of action can also lead to immune-related adverse events (irAEs), which may involve dermatologic, gastrointestinal, hepatic, pulmonary, endocrine, musculoskeletal, cardiovascular, renal, hematologic, neurological, and psychiatric systems. Neurological and neurocognitive irAEs, in particular, are uncommon but potentially devastating and remain poorly characterized.

This study is a hybrid prospective longitudinal observational cohort designed to move beyond reactive identification of irAEs toward proactive prediction and mechanistic understanding. Adult patients with solid tumors initiating a new ICI regimen are enrolled prior to treatment initiation. Longitudinal clinical data, imaging, and biospecimens are collected at predefined intervals and at the time of suspected irAE onset when feasible.

Participants are assigned to event-defined cohorts based on the first grade ≥2 irAE that drives clinical management, including neuro-sensory, gastrointestinal/hepatic, rheumatologic/musculoskeletal, vascular/renal, hematologic, multi-organ, or control (no significant irAE) cohorts. Deep phenotyping and multi-omics analyses-including immune cell profiling, proteomics, metabolomics, and microbiome analyses-are performed to identify biomarkers associated with irAE risk, severity, and outcomes.

Enrollment: 940 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

940 participants in 7 patient groups

Neuro-Sensory irAE Cohort

Description:

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

Gastrointestinal and Hepatic irAE Cohort

Description:

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

Rheumatology and Musculoskeletal irAE Cohort

Description:

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

Vascular and Renal irAE Cohort

Description:

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

Hematologic irAE Cohort

Description:

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

Multi-Organ irAE Cohort

Description:

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

Control Cohort

Description:

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