dc.date.accessioned | 2024-03-13T18:21:51Z | |
dc.date.available | 2024-03-13T18:21:51Z | |
dc.date.created | 2023-10-12T08:49:51Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Ellingsen, Espen Basmo O'Day, Steven Mezheyeuski, Artur Gromadka, Agnieszka Clancy, Trevor Kristedja, Timothy S. Milhem, Mohammed Zakharia, Yousef . Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial. Clinical Cancer Research. 2023, 29(16), 3026-3036 | |
dc.identifier.uri | http://hdl.handle.net/10852/109522 | |
dc.description.abstract | Abstract
Purpose:
Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased antitumor T-cell responses may confer increased antitumor activity in patients with less immunogenic tumors, a subgroup expected to achieve reduced benefit from CPIs alone. In this trial, a telomerase-based vaccine was combined with pembrolizumab to assess the safety and clinical activity in patients with melanoma.
Patients and Methods:
Thirty treatment-naïve patients with advanced melanoma were enrolled. Patients received intradermal injections of UV1 with adjuvant GM-CSF at two dose levels, and pembrolizumab according to the label. Blood samples were assessed for vaccine-induced T-cell responses, and tumor tissues were collected for translational analyses. The primary endpoint was safety, with secondary objectives including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).
Results:
The combination was considered safe and well-tolerated. Grade 3 adverse events were observed in 20% of patients, with no grade 4 or 5 adverse events reported. Vaccination-related adverse events were mostly mild injection site reactions. The median PFS was 18.9 months, and the 1- and 2-year OS rates were 86.7% and 73.3%, respectively. The ORR was 56.7%, with 33.3% achieving complete responses. Vaccine-induced immune responses were observed in evaluable patients, and inflammatory changes were detected in posttreatment biopsies.
Conclusions:
Encouraging safety and preliminary efficacy were observed. Randomized phase II trials are currently ongoing. | |
dc.language | EN | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial | |
dc.title.alternative | ENEngelskEnglishClinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial | |
dc.type | Journal article | |
dc.creator.author | Ellingsen, Espen Basmo | |
dc.creator.author | O'Day, Steven | |
dc.creator.author | Mezheyeuski, Artur | |
dc.creator.author | Gromadka, Agnieszka | |
dc.creator.author | Clancy, Trevor | |
dc.creator.author | Kristedja, Timothy S. | |
dc.creator.author | Milhem, Mohammed | |
dc.creator.author | Zakharia, Yousef | |
cristin.unitcode | 185,53,49,12 | |
cristin.unitname | Institutt for kreftforskning | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2183955 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Clinical Cancer Research&rft.volume=29&rft.spage=3026&rft.date=2023 | |
dc.identifier.jtitle | Clinical Cancer Research | |
dc.identifier.volume | 29 | |
dc.identifier.issue | 16 | |
dc.identifier.startpage | 3026 | |
dc.identifier.endpage | 3036 | |
dc.identifier.doi | https://doi.org/10.1158/1078-0432.CCR-23-0416 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1078-0432 | |
dc.type.version | PublishedVersion | |