Abstract
A phase I clinical trial investigating the telomerase vaccine UV1 in combination with pembrolizumab in patients with advanced melanoma
Journal of clinical oncology, Vol.39(15_suppl), pp.2620-2620
05/20/2021
DOI: 10.1200/JCO.2021.39.15_suppl.2620
Abstract
2620
Background: UV1, a telomerase peptide-based vaccine, consists of 3 long peptides (15-30 aa) representing a 54 aa sequence in the catalytic unit of the reverse transcriptase subunit of telomerase (hTERT). UV1 contains both CD4 and CD8 epitopes, and immunogenicity is shown in 78% of HLA unselected patients (pts.) in prior studies. UV1 induced expansion of hTERT specific CD4+ T cells that might be relevant in tumors expressing telomerase, theoretically enabling enhanced checkpoint efficacy in pts. with insufficient spontaneously primed T cells. Reciprocally, checkpoint inhibitor may support the UV1-induced T cells and provide increased effector activity, as these cells may be restricted by intrinsic and tumor-induced suppressor mechanisms. Methods: UV1 was combined with standard of care pembrolizumab in pts. with advanced melanoma. The primary objective of this phase I, multicenter study (NCT03538314), was to evaluate safety and tolerability of UV1 in combination with standard pembrolizumab. Secondary objective was evaluation of response rate (RR) according to iRECIST. Pts. received, in a serial manner, adjuvant GM-CSF and UV1 (300μg) intradermally followed by pembrolizumab. The first 3 UV1/GM-CSF doses were given during week 1, and from week 2 in combination with pembrolizumab (Q3W). Two different doses of GM-CSF were investigated: 37.5μg (20 pts. cohort 1) and 75μg (10 pts. cohort 2). Totally 8 UV1/GM-CSF vaccinations per pt. were planned (14 weeks). Results: In total 30 pts. were enrolled; cohort 1 (N = 20); cohort 2 (N = 10). The abstract reports cohort 1 results. The majority of adverse events (AEs) reported was grade 1 or 2 (48%, 41%). Main AEs were fatigue (8%), injection site reaction (5%), diarrhea (4%) and pyrexia (3%). 18% and 30% of AEs were possibly/definitely related to UV1 or pembrolizumab, respectively. Three patients experienced SAE, one (inflammatory arthritis) was considered possibly related to UV1. No severe allergic reactions were observed. Pembrolizumab was continued after completion of UV1 treatment in 14 pts. for a mean of 8.2 months (range 3-21). Four pts. discontinued pembrolizumab due to PD, one for irAE and one for unknown reason. The RR was 60%, with 5 CRs, and the 1-year survival rate 85 %. Conclusions: Results from cohort 1 (N = 20) show that the treatment of UV1 together with pembrolizumab was safe and well tolerated in patients with advanced melanoma. Updated data with minimum 18 months follow-up will be presented at the conference. Cohort 2 results will be presented at a later stage. Clinical trial information: NCT03538314. [Table: see text]
Details
- Title: Subtitle
- A phase I clinical trial investigating the telomerase vaccine UV1 in combination with pembrolizumab in patients with advanced melanoma
- Creators
- Yousef Zakharia - University of IowaSteven O'Day - Saint John's Health CenterWenche Rasch - UltimovacsMohammed M. Milhem - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.39(15_suppl), pp.2620-2620
- DOI
- 10.1200/JCO.2021.39.15_suppl.2620
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Ultimovacs ASA
- Language
- English
- Date published
- 05/20/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363160802771
Metrics
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