Abstract 3996
Background
This ongoing trial is investigating the safety and efficacy of combining the therapeutic cancer vaccine UV1 with the anti-PD-1 mAb pembrolizumab. UV1 is a peptide-based vaccine directed against telomerase, an essential enzyme for unlimited cell-division and a hallmark of cancer. Due to its selective expression, telomerase serves as a unique cancer antigen. UV1 consists of 3 long peptides (15-30 aa) representing fragments of the reverse transcriptase subunit of telomerase (hTERT). The peptides contain both CD4 and CD8 epitopes and are shown to be immunogenic in 78% of HLA unselected patients across different cancer types. UV1 induces hTERT-specific tumor-reactive T cells, and has the potential to induce epitope spreading. UV1 can increase the efficacy of checkpoint inhibitors in patients with insufficient numbers of T cells spontaneously primed by tumor antigens. Reciprocally, the efficacy of UV1 may be enhanced by checkpoint inhibitors, since the effector activity of UV1-induced T cells will be restricted by intrinsic and tumor-induced suppressor mechanisms. UV1 and pembrolizumab thus have the potential to produce synergistic immunological activity which may provide increased clinical benefit as compared to pembrolizumab alone.
Trial design
The ongoing phase I, open-label, multicenter study is planned to include 20 patients with untreated unresectable or metastatic melanoma. UV1 (300 μg) with GM-CSF (37,5 μg) as adjuvant is administered intradermally for a total of 8 doses, 3 doses during week 1, and one dose during week 2, 3, 8, 11 and 14. Pembrolizumab is administered every third week starting week 2 for up to two years or until progressive disease. Patients are followed for up to 2 years after the first UV1 dose. The primary objective of the study is to evaluate the safety and tolerability of the UV1 and pembrolizumab therapy. Secondary objectives are UV1 vaccine-specific immune responses and evaluation of tumor response (RECIST). Samples of blood, feces, and tumor tissue are collected for translational research purposes.
Clinical trial identification
NCT03538314.
Editorial acknowledgement
Legal entity responsible for the study
Ultimovacs AS.
Funding
Ultimovacs AS.
Disclosure
Y. Zakharia: Advisory / Consultancy: Amegen; Advisory / Consultancy: Roche Diagnostics; Advisory / Consultancy: Novartis; Advisory / Consultancy: JNJ; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Castle Bioscience; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bayer; Advisory / Consultancy: Array. All other authors have declared no conflicts of interest.
Resources from the same session
3664 - Longitudinal changes in cell-free DNA (cfDNA) methylation levels identify early non-responders to treatment in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3212 - Multigene panel testing results for hereditary breast cancer in 1325 individuals: implications for gene selection and considerations for guidelines.
Presenter: Georgios Tsaousis
Session: Poster Display session 3
Resources:
Abstract
2591 - PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Presenter: Julia Quintanilha
Session: Poster Display session 3
Resources:
Abstract
4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.
Presenter: Nuria Chic
Session: Poster Display session 3
Resources:
Abstract
3439 - Early on-treatment vs pre-treatment tumor transcriptomes as predictors of response to neoadjuvant therapy for HER2-positive inflammatory breast cancer
Presenter: Sonia Pernas
Session: Poster Display session 3
Resources:
Abstract
2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)
Presenter: Claudia Cardone
Session: Poster Display session 3
Resources:
Abstract
4061 - Prevalence of EGFR mutations and its correlation with Egyptian patients’ human kinetics (PEEK Study)
Presenter: Adel Ibrahim
Session: Poster Display session 3
Resources:
Abstract
2547 - Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)
Presenter: Sergio Rutella
Session: Poster Display session 3
Resources:
Abstract
4671 - Clinicopathological and molecular criteria assessment for the screening of hypermutated proficient mismatch repair (pMMR) colorectal cancers (CRC) with exonucleasic domain POLE (edPOLE) mutations (mt).
Presenter: Benoit Rousseau
Session: Poster Display session 3
Resources:
Abstract
3862 - Tumor mutation burden and microsatellite instability in colorectal cancer
Presenter: Francesca Fenizia
Session: Poster Display session 3
Resources:
Abstract