Phase 2 Single Arm Study of Nivolumab and Ipilimumab (Nivo/Ipi) in Previously Treated Classical Kaposi Sarcoma (cKS)

Annals of Oncology Manuscript
Authors A. Zer O. Icht L. Yosef D. Avram O. Jacobi E. Fenig N. Kurman I. Peretz S. Shamai O. Merimsky E. Ben-Ami R. Shapira Frommer A.E. Schwarzbach H. Bernstine R. Weitzen O. Vornicova G. Bar-Sela S.M. Stemmer M. Lotem


Classical Kaposi Sarcoma (cKS) is a rare HHV8-associated sarcoma with limited treatment options. We evaluated the efficacy and safety of nivolumab in combination with ipilimumab (Nivo/Ipi) in patients with previously treated progressive cKS.

Patients and Methods

cKS pts with progressive disease after > 1 lines of systemic therapy and measurable disease by PET/CT and/or physical examination received nivolumab 240mg every two weeks and ipilimumab 1mg/kg every six weeks until progression or toxicity for a maximum of 24 months. The primary endpoint was overall response rate (ORR); secondary endpoints included 6-months progression free survival rate (PFS) and safety. Immune correlates were explored using IHC, DNAseq (596/648 genes) and RNAseq (exome capture transcriptome) of tumor specimens and matched blood.


Eighteen male patients (median age 76.5) were enrolled between April 2018 and Dec 2020. At a median follow up of 24.4 months, ORR by RECIST v1.1 was 87%. Metabolic complete response as assessed by PET CT was observed in 8 of 13 (62%) evaluable patients. 6/13 achieved pathological CR post treatment. In two patients, palliative limb amputation was prevented. Median PFS was not reached. The 6mo and 12m PFS rate was 76.5% and 58.8%, respectively. Only four patients (22%) experienced grade 3-4 adverse events. The most frequent genomic alteration was biallelic copy number loss of FOX1A gene. The majority of tumors carried a low TMB, were microsatellite stable (MSS), MMR proficient, did not express PD-L1 and displayed only low lymphocytic infiltrates, rendering them immunologically “cold”.


This prospectively designed phase II study of nivolumab and ipilimumab demonstrates promising activity of this combination in progressive cKS representing a new treatment option in this population.