ITHACA

Key outcome parameters

Primary endpoints:

• Difference in medion non-calcified coronary plaque volume between baseline and 1-year follow-up on computed tomography angiography (CCTA)

Secondary endpoints:

• Atherosclerotic plaque changes (i.e. fatenuation index, non-calcified plaques);
• Plasma and fecal biomarker changes associated with immunothrombosis;
• Incidence of arterial and venous thromboembolic events;
• Incidence of immune related adverse events (irAE)

Intervention

All patients will undergo CCTA scanning at baseline and after 1 year. Blood will be drawn at baseline, 3 and 12 months after start of therapy. Feces will be collected at baseline and after 1 year.

Key inclusion criteria

Inclusion criteria:

• Confirmed diagnosis of non-small-cell lung carcinoma planned for pembrolizumab (high PD-L1 expression based on TPS ≥50%, stage IV), durvalumab (stage III) or other than ICI (controls);
• Age ≥50 years;
• Prior to start of new therapy

Key exclusion criteria

Exclusion criteria:

• ICI therapy in previous 12 months;
• Suspected or confirmed viral, fungal, or bacterial infectious disease;
• Use of immunosuppressive therapy prior to ICI start;
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2;
• Known allergy to iodinated contrast agents;
• Atrial fibrillation.