Immune-related Adverse Event
Conditions
Keywords
Therapeutic plasma exchange, TPE, Immune Checkpoint Inhibitors, Immune-related Adverse Events, Pharmacokinetics, Pembrolizumab, Nivolumab, Ipilimumab
Brief summary
The purpose of this study is to characterize the pharmacokinetics of one or more ICIs during and after TPE/PLEX in patients with severe irAEs.
Detailed description
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy across multiple tumor types; however, their mechanism of action-releasing immune inhibition-inevitably predisposes patients to immune-related adverse events (irAEs). These toxicities occur in up to 74% of patients treated with PD-(L)1 inhibitors and in more than 90% of those receiving combination therapy, with grade 3-5 events in 14-55% of cases depending on regimen and tumor type. Immune-related adverse events caused by ICIs often present with a spectrum of clinical manifestations that closely resemble primary autoimmune diseases affecting multiple organ systems, including the skin, gastrointestinal tract, liver, lung, and nervous system. Therapeutic plasma exchange is an established therapeutic procedure in selected immune-mediated diseases where rapid removal of circulating pathogenic material is clinically relevant (13). In these settings, TPE/PLEX can remove circulating antibodies, immune complexes, complement-related factors, inflammatory mediators, and therapeutic monoclonal antibodies. These precedents support the biologic rationale for considering TPE/PLEX in selected severe irAEs when treating clinicians believe that removal of circulating ICI and/or soluble immune mediators may be clinically appropriate. Immune-related adverse events are an acceptable indication for TPE/PLEX, and the procedure may be considered based on individual patient circumstances and treating-team judgment. The purpose of this small, single-arm, open-label Phase 1 pharmacokinetic study is to characterize ICI concentrations during and after TPE in patients with severe irAEs. Timed PK blood samples will be collected during and after TPE/PLEX according to the study PK sampling plan. Clinically relevant information will be collected from participant's medical record throughout the study.
Interventions
Therapeutic plasma exchange (using the Spectra Optia Apheresis System) will be done according to standard of care.
Sponsors
University of Chicago
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults ≥ 18 years of age * Diagnosis of any malignancy. * Receiving or recently received an immune checkpoint inhibitor, including anti-PD-1, anti-PD-L1, anti-CTLA-4, or combination ICI therapy. Eligible agents may include, but are not limited to, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, cemiplimab, dostarlimab, and ipilimumab. * Received an ICI within 12 weeks prior to planned enrollment, or within a timeframe considered appropriate by the PI for PK evaluation based on the specific ICI agent, dosing history, and assay feasibility. * Suspected or confirmed severe or clinically significant immune-related adverse event for which the treating clinical team considers TPE/PLEX clinically appropriate. * Planned to undergo or currently undergoing TPE/PLEX at the University of Chicago Medicine. * Approval from the patient's primary clinical service for study participation. * Able to provide written informed consent, or has a legally authorized representative able to provide consent if permitted by the IRB-approved consent process. * In the opinion of the treating team and study team, PK blood sample collection can be performed without delaying or interfering with clinically indicated care.
Exclusion criteria
* No prior exposure to an immune checkpoint inhibitor. * TPE/PLEX is being performed for an indication unrelated to a suspected or confirmed ICI-associated immune-related adverse event. * Inability to provide informed consent and no legally authorized representative is available, if applicable. * PK blood sample collection is not feasible without delaying, altering, or interfering with clinically indicated care. * Any condition that, in the opinion of the investigator or treating team, would make participation in the research procedures unsafe or inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in circulating ICI concentration during and after TPE/PLEX | Baseline to Day 90 | This will be measured by ICI concentration before and after TPE/PLEX sessions when paired samples are available, Percent change in ICI concentration from pre- to post-TPE/PLEX, and ICI concentration-time profiles across available PK sampling time points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the feasibility of conducting a small PK-focused Phase 1 study of TPE/PLEX in patients with severe irAEs. | Baseline to Day 90 | This will be measured by the Proportion of eligible patients successfully identified and approached, approached patients who consent to study participation, enrolled patients who undergo at least one TPE/PLEX session, enrolled patients with at least one evaluable PK sample, enrolled patients with paired pre-/post-TPE/PLEX PK samples |
Countries
United States
Contacts
CONTACTPankti Reid
CONTACTMohamed Ali
PRINCIPAL_INVESTIGATORPankti Reid
University of Chicago
Outcome results
None listed