Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS)

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Classical Kaposi sarcoma (cKS) is a rare human herpesvirus 8-associated sarcoma with limited treatment options. We evaluated the efficacy and safety of nivolumab in combination with ipilimumab in patients with previously treated progressive cKS. Patients and methods: cKS patients with progressive disease after one or more lines of systemic therapy and measurable disease by positron emission tomography/computed tomography and/or physical examination received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until progression or toxicity for a maximum of 24 months. The primary endpoint was overall response rate; secondary endpoints included 6-month progression-free survival (PFS) rate and safety. Immune correlates were explored using immunohistochemistry, DNA sequencing (596/648 genes) and RNA sequencing (whole transcriptome hybrid capture) of tumor specimens and matched blood. Results: Eighteen male patients (median age 76.5 years) were enrolled between April 2018 and December 2020. At a median follow up of 24.4 months, overall response rate by RECIST v1.1 was 87%. Metabolic complete response as assessed by positron emission tomography/computed tomography was observed in 8 of 13 (62%) assessable patients. Some 6/13 achieved pathological complete response after treatment. In two patients, palliative limb amputation was prevented. Median PFS was not reached. The 6- month and 12-month 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 the FOX1A gene. The majority of tumors carried a low tumor mutational burden, were microsatellite stable, mismatch repair proficient, did not express programmed death-ligand 1, and displayed only low lymphocytic infiltrates, rendering them immunologically ‘cold’. Conclusions: 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.

Original languageEnglish
Pages (from-to)720-727
Number of pages8
JournalAnnals of Oncology
Issue number7
StatePublished - Jul 2022
Externally publishedYes


  • Kaposi sarcoma
  • human herpesvirus 8
  • immune checkpoint inhibitor
  • immunotherapy


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