Background: CKS is an angioproliferative mesenchymal neoplasm causatively associated with human herpes virus 8 infection. Though recombinant IFNa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation in CKS therapy. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated progressive CKS (NCT03219671). Methods: CKS pts with progressive disease after ≥ 1 line of systemic therapy and measurable disease by PET/CT and/or physical exam received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint was overall response rate (ORR), secondary endpoints include 6-months progression free survival rate (PFS) and safety. Correlative studies in tumor and serum samples are ongoing using an NGS panel for DNA and RNA and proteomic staining (Tempus Labs Inc). A pre-planned interim analysis was conducted after the first ten enrolled patients for efficacy and toxicity evaluation. Results: Ten patients were enrolled and evaluable between April2018 and February2019. Median age 72 (61-79), all male. At a median FU of 3.1 months (1.5-8.1) ORR was 50% (4 patients PR, 1 patient CR, 5 patients SD). Median PFS was not reached however no progression of disease was documented so far. The safety profile was as expected with all patients experiencing G1 toxicity and four patients with G2 toxicity (1 ALT/AST increase, 2 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in one patient (G2 LFT increase. maintaining CR 4 months after treatment discontinuation). Correlative results are pending. Conclusions: The interim analysis in this prospectively designed phase II study of nivolumab and low-dose ipilimumab demonstrate promising activity in progressive CKS, with 50% ORR and no events of progression thus far. We expect to report the updated efficacy and correlative data. Clinical trial information: NCT03219671