Journal article
Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial
Clinical cancer research, Vol.29(16), pp.3026-3036
08/15/2023
DOI: 10.1158/1078-0432.CCR-23-0416
PMCID: PMC10425723
PMID: 37378632
Abstract
Purpose: Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottle-neck 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, atelomerase-based vaccine was combined with pembrolizumab to assess the safety and clinical activity in patients with melanoma. Patients and Methods: Thirty treatment-na ⠂eurove 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 sur-vival (PFS), overall survival (OS), and objective response rate (ORR).Results: The combination was considered safe and well-tolerat-ed. 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.
Details
- Title: Subtitle
- Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial
- Creators
- Espen B. Ellingsen - Oslo Univ Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, NorwaySteven O'Day - Saint John's Health CenterArtur MezheyeuskiAgnieszka GromadkaTrevor ClancyTimothy S. Kristedja - Saint John's Health CenterMohammed Milhem - University of IowaYousef Zakharia - Univ Iowa, Iowa City, IA USA
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.29(16), pp.3026-3036
- DOI
- 10.1158/1078-0432.CCR-23-0416
- PMID
- 37378632
- PMCID
- PMC10425723
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 11
- Grant note
- Research Council of Norway Ultimovacs ASA, Oslo, Norway
- Language
- English
- Date published
- 08/15/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984463081302771
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