Background: Pegilodecakin (PEG), a pegylated recombinant human interleukin-10, has demonstrated clinical benefit and manageable toxicity in advanced RCC (Naing et al. 2016 JCO, Naing et al. 2019 Lancet Oncol). As part of the multi-arm (arm A to J) phase 1 IVY study, PEG alone (Part A) or in combination with pazopanib (Part G) or anti-PD-1 (pembrolizumab or nivolumab; Parts H+I) were investigated in heavily pretreated RCC patients (pts). Methods: In a phase 1/1b study which enrolled 353 pts in the US from 2013 to 2017, we analyzed treatment-related adverse events (TRAEs) graded by CTCAE v 4.02, tumor response by irRC, progression-free survival (PFS), and overall survival (OS) for all the advanced RCC pts who received PEG-containing treatment (n=66). Data cut-off was February 19, 2019. Results: Sixty six heavily pretreated RCC pts received PEG alone (n=24, 1-20 µg/kg), with pazopanib (n=4, 10µg/kg), with pembrolizumab (n=9, 10-20 µg/kg), or with nivolumab (n=29, 10-20 µg/kg). Most pts were male (70%), median age 62.5 years, initially diagnosed as stage IV (42%) with clear cell histology (64%), ECOG performance status of 1 (58%), and intermediate/poor (73%/14%) risk per IMDC category. Patients received a median number of 2 prior therapies. Most common grade 3/4 TRAEs were anemia (32%), thrombocytopenia (15%), and hypertriglyceridemia (14%). No pts died due to a TRAE. Median follow-up was 31.5 months. Conclusions: PEG alone or in combination with anti-PD-1 or pazopanib suggested some clinical activity with manageable toxicity in advanced RCC pts. These findings support further ongoing studies of PEG combinations in RCC pts. Clinical trial information: NCT02009449.