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

Annals of Oncology, Tempus-authored
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.