Trial Design and Treatment
congenital anomaly/birth defect, death, disability/incapacity
EVENT, ADVERSE EVENT
This was a phase I trial of combination therapy with avelumab and cabozantinib in patients with newly diagnosed mccRCC. Dose-escalation was performed using a standard 3 + 3 design with cabozantinib oral doses of 20, 40, and 60 mg/day plus avelumab 10 mg/kg every 2 weeks in each of the 3 cohorts (Safety assessments included documentation of AEs, physical examination, clinical laboratory tests (hematology labs, hepatic panels, and serum chemistries), and documentation of concurrent medications. A serious adverse event (SAE) was defined as any untoward event that resulted in death, life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or was otherwise considered medically necessary. Immune-related AEs (irAEs) were identified using a pre-specified list of Medical Dictionary for Regulatory Activities (MedDRA) terms, followed by a comprehensive medical review. Infusion-related reactions (IRRs) were analyzed using both a prespecified list of MedDRA preferred terms (reactions occurring post-infusion on the same day or following day) and related signs and symptoms (based on specified MedDRA terms) that occurred on the day of infusion and resolved in ≤ 2 days.