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
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract