Trial Design and Treatment
toxicity, toxicities, DLT
DISEASE PROGRESSION, ADVERSE REACTION
This study was a prospective open-label, nonrandomized phase I study exploring the safety and tolerability of avelumab, an IgG1 mAb that, by binding PD-L1, prevents binding to the PD-1 receptor. The trial was registered on clinicaltrials.gov (NCT03341806). The authors performed the study at a single institution. The study enrolled patients in two successive safety phases: the first cohort of avelumab alone (part A) and the second cohort of MRI-guided LITT followed by avelumab (part B). The study followed a 3+3 design if no more than 0/3 or 1/6 patients experienced dose-limiting toxicities (DLT) in part A. A DLT was defined as a grade ≥3 adverse reaction suspected to be related to avelumab. Avelumab was administered initially at a dose of 10 mg/kg intravenous every 2 weeks and subsequently changed to a 60-minute infusion of 800 mg after the FDA authorized a flat dose for approved indications. Avelumab was given within a week after LITT and every 2 weeks after that until disease progression, intolerable toxicity, or withdrawal of patient consent. However, patients could continue the study treatment following evidence of disease progression if deemed appropriate at the investigator's discretion. If patients became symptomatic and required either initiation or increased doses of dexamethasone, they were allowed to remain in the study and treated with bevacizumab to avoid the immunosuppressive effect of steroid use.