Mini Oral session - Sarcoma Mini Oral session

404O - A phase II single arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated Classical Kaposi Sarcoma (CKS)

Presentation Number
404O
Lecture Time
11:45 AM - 11:50 AM
Speakers
  • Alona Zer
Location
Room 311, Singapore, Singapore, Singapore
Date
Fri, 22.11.2019
Time
11:40 AM - 12:20 PM
Authors
  • Alona Zer
  • Oded Icht
  • Oded Jacobi
  • Eyal Fenig
  • Sivan Shamai
  • Ofer Merimsky
  • Ronnie Shapira
  • Hanna Bernstine
  • Rony Weitzen
  • Olga Vornikova
  • Eytan Ben-Ami
  • Gil Bar-Sela
  • Salomon M. Stemmer
  • Michal Lotem

Abstract

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. 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 (tx) progressive CKS.

Methods

CKS pts with progressive disease after > 1 line of systemic tx 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 (EP) was overall response rate (ORR), secondary EP include 6-months progression free survival rate (PFS) and safety. Exploratory EP included PD-L1/MMR IHC, DNAseq (596 genes)/RNAseq (whole transcriptome) of tissue and matched blood to explore CKS genomic traits and IO correlates: TMB, MSI, dMMR, PD-L1, immune gene expression (PD1, CTLA4, etc) (Tempus Labs, Chicago, IL, USA).

Results

Twelve patients were enrolled and evaluable between Apr2018-Jun2019 and 11 were evaluable for response. Median age 72 (61-81). At a mFU of 6 months ORR was 45% (4 pts PR, 1 pt CR, 6 pts SD). mPFS was not reached, 6-mo PFS rate was 91% (1 out of 11 patients had PD). The safety profile was as expected with three patients with G2 toxicity (1 ALT/AST increase, 1 asymptomatic lipase increase) and two patients with G3 toxicity (1 colitis, 1 asymptomatic lipase increase) . One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in one pt (G2 LFT increase. maintaining CR 4 months after treatment discontinuation). Correlative results are available for four patients showing negative PDL1 IHC in all, low TMB, MS-S, but marked overexpression of CTLA4, PD1 and PDL1.

Conclusions

The interim analysis in this prospectively designed phase II study of nivo/ipi demonstrate promising activity in progressive CKS, with 45% ORR and a 6mo PFS rate of 91%. Toxicity profile as expected in this class of drugs. Correlative studies are preliminary but warrants further investigation into immune gene expression profiles.

Clinical trial identification

NCT03219671.

Editorial acknowledgement

None

Legal entity responsible for the study

The authors.

Funding

BMS Rabin Medical Center.

Disclosure

A. Zer: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AZ. All other authors have declared no conflicts of interest.

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