Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer

Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple...

Full description

Bibliographic Details
Main Authors: Paal F. Brunsvig, Tormod Kyrre Guren, Marta Nyakas, Claudius H. Steinfeldt-Reisse, Wenche Rasch, Jon Amund Kyte, Hedvig Vidarsdotter Juul, Steinar Aamdal, Gustav Gaudernack, Else Marit Inderberg
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2020.572172/full
_version_ 1818926150731169792
author Paal F. Brunsvig
Tormod Kyrre Guren
Marta Nyakas
Claudius H. Steinfeldt-Reisse
Wenche Rasch
Jon Amund Kyte
Hedvig Vidarsdotter Juul
Steinar Aamdal
Gustav Gaudernack
Else Marit Inderberg
author_facet Paal F. Brunsvig
Tormod Kyrre Guren
Marta Nyakas
Claudius H. Steinfeldt-Reisse
Wenche Rasch
Jon Amund Kyte
Hedvig Vidarsdotter Juul
Steinar Aamdal
Gustav Gaudernack
Else Marit Inderberg
author_sort Paal F. Brunsvig
collection DOAJ
description Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials. Eighteen non-HLA-typed patients with stage III/IV NSCLC with no evidence of progression after prior treatments, were enrolled in a phase I dose-escalation study of UV1 vaccination with GM-CSF as adjuvant, evaluating safety, immune response, and long-term clinical outcome. Treatment with UV1 was well tolerated with no serious adverse events observed. Seventeen patients were evaluable for tumor response; 15 patients had stable disease as best response. The median progression free survival (PFS) was 10.7 months, and the median overall survival (OS) was 28.2 months. The OS at 4 years was 39% (7/18). Five patients are alive (median survival 5.6 years), and none of these are known to have received checkpoint therapy after vaccination. UV1 induced specific T-cell responses in the majority (67%) of patients. Immune responses were dynamic and long lasting. Both immune response (IR) and OS were dose related. More patients in the highest UV1 dosage group (700 μg) developed IRs compared to the other groups, and the IRs were stronger and occurred earlier. Patients in this group had a 4-year OS of 83%. The safety and clinical outcome data favor 700 μg as the preferred UV1 dose in this patient population. These results provide a rationale for further clinical studies in NSCLC with UV1 vaccination in combination with immune checkpoint blockade.Clinical Trial Registrationhttps://www.clinicaltrials.gov, identifier NCT0178909.
first_indexed 2024-12-20T02:52:33Z
format Article
id doaj.art-41a6f845f5a44e1880c305a1ad02c3af
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-12-20T02:52:33Z
publishDate 2020-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-41a6f845f5a44e1880c305a1ad02c3af2022-12-21T19:55:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.572172572172Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung CancerPaal F. Brunsvig0Tormod Kyrre Guren1Marta Nyakas2Claudius H. Steinfeldt-Reisse3Wenche Rasch4Jon Amund Kyte5Hedvig Vidarsdotter Juul6Steinar Aamdal7Gustav Gaudernack8Else Marit Inderberg9Department of Clinical Cancer Research, Oslo University Hospital–The Norwegian Radium Hospital, Oslo, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital–The Norwegian Radium Hospital, Oslo, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital–The Norwegian Radium Hospital, Oslo, NorwayDepartment of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, NorwayUltimovacs ASA, Oslo, NorwayDepartment of Clinical Cancer Research, Oslo University Hospital–The Norwegian Radium Hospital, Oslo, NorwayDepartment of Cellular Therapy, Oslo University Hospital–The Norwegian Radium Hospital, Oslo, NorwayUltimovacs ASA, Oslo, NorwayUltimovacs ASA, Oslo, NorwayDepartment of Cellular Therapy, Oslo University Hospital–The Norwegian Radium Hospital, Oslo, NorwayHuman telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials. Eighteen non-HLA-typed patients with stage III/IV NSCLC with no evidence of progression after prior treatments, were enrolled in a phase I dose-escalation study of UV1 vaccination with GM-CSF as adjuvant, evaluating safety, immune response, and long-term clinical outcome. Treatment with UV1 was well tolerated with no serious adverse events observed. Seventeen patients were evaluable for tumor response; 15 patients had stable disease as best response. The median progression free survival (PFS) was 10.7 months, and the median overall survival (OS) was 28.2 months. The OS at 4 years was 39% (7/18). Five patients are alive (median survival 5.6 years), and none of these are known to have received checkpoint therapy after vaccination. UV1 induced specific T-cell responses in the majority (67%) of patients. Immune responses were dynamic and long lasting. Both immune response (IR) and OS were dose related. More patients in the highest UV1 dosage group (700 μg) developed IRs compared to the other groups, and the IRs were stronger and occurred earlier. Patients in this group had a 4-year OS of 83%. The safety and clinical outcome data favor 700 μg as the preferred UV1 dose in this patient population. These results provide a rationale for further clinical studies in NSCLC with UV1 vaccination in combination with immune checkpoint blockade.Clinical Trial Registrationhttps://www.clinicaltrials.gov, identifier NCT0178909.https://www.frontiersin.org/articles/10.3389/fimmu.2020.572172/fullnon-small cell lung cancerhuman telomerase reverse transcriptasepeptidevaccine monotherapydose responseclinical efficacy
spellingShingle Paal F. Brunsvig
Tormod Kyrre Guren
Marta Nyakas
Claudius H. Steinfeldt-Reisse
Wenche Rasch
Jon Amund Kyte
Hedvig Vidarsdotter Juul
Steinar Aamdal
Gustav Gaudernack
Else Marit Inderberg
Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
Frontiers in Immunology
non-small cell lung cancer
human telomerase reverse transcriptase
peptide
vaccine monotherapy
dose response
clinical efficacy
title Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
title_full Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
title_fullStr Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
title_full_unstemmed Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
title_short Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer
title_sort long term outcomes of a phase i study with uv1 a second generation telomerase based vaccine in patients with advanced non small cell lung cancer
topic non-small cell lung cancer
human telomerase reverse transcriptase
peptide
vaccine monotherapy
dose response
clinical efficacy
url https://www.frontiersin.org/articles/10.3389/fimmu.2020.572172/full
work_keys_str_mv AT paalfbrunsvig longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT tormodkyrreguren longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT martanyakas longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT claudiushsteinfeldtreisse longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT wencherasch longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT jonamundkyte longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT hedvigvidarsdotterjuul longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT steinaraamdal longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT gustavgaudernack longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer
AT elsemaritinderberg longtermoutcomesofaphaseistudywithuv1asecondgenerationtelomerasebasedvaccineinpatientswithadvancednonsmallcelllungcancer