Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS).
Kaposi sarcoma
human herpesvirus 8
immune checkpoint inhibitor
immunotherapy
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
22
01
2022
revised:
12
03
2022
accepted:
14
03
2022
pubmed:
28
3
2022
medline:
22
6
2022
entrez:
27
3
2022
Statut:
ppublish
Résumé
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. 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. 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'. 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.
Sections du résumé
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.
Identifiants
pubmed: 35339649
pii: S0923-7534(22)00391-X
doi: 10.1016/j.annonc.2022.03.012
pii:
doi:
Substances chimiques
Ipilimumab
0
Nivolumab
31YO63LBSN
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
720-727Informations de copyright
Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure AZ: no conflict of interest (COI) within the submitted work. COI outside this work: consulting fees from Roche, Merck Sharp & Dohme (MSD), AstraZeneca, Novartis, Pfizer. Honoraria from Roche, Takeda, AstraZeneca. Participation in advisory boards: AstraZeneca, Novartis. Stock options: Nixio. GB: no COI within the submitted work. COI outside this work: consulting fees from Novartis, Dexcel, Abbot. Honoraria from Bristol Myers Squibb (BMS), MSD, Merck, Novartis, Dexcel, Medison, Boehringer, Sanofi. Research grants: Oncotest-Ranuim, Syqe. SMS: no COI within the submitted work. COI outside this work: consulting fees from PSI. ML: no COI within the submitted work. COI outside this work: consulting fees from Merck, BMS, Sanofi, Oncohost. Honoraria: none. Support for attending meetings: Merck, BMS. Patents: WO2012/156969, 17/05/2012; WO/2015/104711 08/01/2015, WO 2016/027273 19/08/2015. Participation in advisory boards or DSM: Merck. All other authors have declared no conflicts of interest.