NCT Number: NCT07357636
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.
Interested in participating?
Request Info18 year and older
All sexes
Observational
First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Time frame: From irAE diagnosis through up to 24 months of follow-up
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.
Time frame: 12 weeks after irAE diagnosis
Among participants with immune-mediated neurological events (e.g., encephalitis, myelitis, plexopathy), functional status will be assessed using the Modified Rankin Scale. An mRS score ≤2 (slight disability, able to live independently) is a widely accepted threshold for favorable neurological outcome in neuroimmunology clinical trials.
Time frame: 12 weeks after irAE diagnosis
Among participants with immune-mediated peripheral neuropathy, electrophysiologic improvement will be assessed using nerve conduction studies and electromyography. Objective improvement is defined as ≥20% improvement in motor or sensory nerve action potential amplitude or conduction velocity compared with the acute phase, according to EFNS/PNS criteria.
Time frame: 8 weeks after initiation of targeted treatment
Among participants with immune-mediated major depressive episodes, depressive symptoms will be assessed using the PHQ-9. A score <10 represents remission or mild symptoms and is an internationally accepted threshold distinguishing clinically significant depression from response/remission.
Time frame: 12 weeks after irAE diagnosis
Among participants with immune-mediated cognitive impairment, standardized neuropsychological test batteries (including the Hopkins Verbal Learning Test-Revised and Trail Making Test Part B) will be administered. Clinically meaningful cognitive improvement is defined as ≥0.5 standard deviation improvement from the acute phase in at least two distinct cognitive domains.
Time frame: 2 weeks after initiation of immunosuppressive therapy
Among participants with immune-mediated colitis, clinical remission will be assessed. ≤3 bowel movements per day without hematochezia is a widely accepted clinical remission criterion in colitis clinical trials.
Time frame: 4 weeks after initiation of immunosuppressive therapy
Among participants with immune-mediated hepatitis, biochemical remission will be assessed. ALT ≤1.5 × ULN is a commonly accepted biochemical remission criterion in drug-induced liver injury trials.
Time frame: 12 weeks after initiation of immunosuppressive therapy
Among participants with immune-mediated inflammatory arthritis, disease activity will be assessed using the CDAI. A CDAI score ≤10 defines low disease activity and is an established rheumatologic threshold.
Time frame: 12 weeks after irAE diagnosis
Among participants with immune-mediated myositis, muscle strength will be assessed using the MMT-8 score. A ≥20% improvement from the acute phase is an established clinically meaningful threshold in myositis trials.
Time frame: 12 weeks after irAE diagnosis
Among participants with immune-mediated nephritis, renal recovery will be assessed. Serum creatinine recovery to within 1.3 × baseline represents a stringent and clinically meaningful recovery criterion per KDIGO acute kidney injury guidelines.
Time frame: Within 12 weeks after initiation of first-line immunosuppressive therapy
Among participants with immune-mediated cytopenias, hematologic remission is defined as maintenance of CTCAE v5.0 grade ≤1 blood counts (e.g., platelets ≥75 ×10⁹/L, absolute neutrophil count ≥1.5 ×10⁹/L) for at least 4 weeks without ongoing transfusion or growth factor support.
Time frame: 2 weeks after initiation of treatment
Among participants with immune-mediated hemolytic anemia, hemolysis control is defined as normalization of lactate dehydrogenase with stable hemoglobin levels for ≥7 days without transfusion support.
Time frame: Within 4 weeks after initiation of combined immunosuppressive therapy
Among participants with multi-organ irAEs, overall toxicity control is defined as absence of any new or worsening grade ≥3 irAE in any organ system following initiation of treatment.
Time frame: irAE diagnosis through resolution or up to 24 weeks
The proportion of participants requiring intensive care unit admission due to the severity of multi-organ immune-related adverse events will be recorded as an objective marker of disease severity.
Time frame: From ICI initiation through 90 days after last dose
Among participants who do not develop grade ≥2 irAEs, treatment tolerability will be assessed as the time from ICI initiation to first occurrence of grade ≥2 irAE, disease progression, death, or treatment discontinuation.
Time frame: From ICI initiation through 90 days after last dose
Among participants without grade ≥2 irAEs, the proportion completing the planned ICI treatment course as scheduled will be recorded as a complementary measure of treatment tolerability.
Contact information is provided by the study sponsor or research team.
Shantou University Medical College
Other
Longitudinal Cohort Study of Immune-Related Adverse Events in Solid Tumor Patients Receiving Immune Checkpoint Inhibitors, With Deep Phenotyping and Multi-Omics Biomarker Discovery
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