Abstract 5423
Background
Enadenotucirev (EnAd) is a tumor selective Ad11/Ad3 group B adenovirus that has demonstrated pre-clinical activity in a model of platinum-resistant ovarian cancer. Synergy has also been reported between oncolytic adenoviruses and microtubule manipulating drugs such as paclitaxel (Pxl). This study aims to establish the tolerability and preliminary efficacy of EnAd delivered in combination with Pxl. Here we present data from the intravenous (IV) dose expansion group.
Methods
Patients with platinum-resistant or refractory ovarian cancer received a minimum of two 28-days cycles of IV infusional EnAd (1x1012 viral particles) on days 1, 3 and 5, and IV Pxl (80mg/m2) on days 9, 16 and 23. Baseline and on-treatment biopsies were taken. Primary endpoint was safety and tolerability; additional endpoints included, response rate (RECISTv1.1/GCIG CA125 criteria) and duration of response.
Results
Twenty patients, median age 60.5 years (range 37-78) who had received a median of 4 prior lines of therapy (range 1-12) were enrolled. Adverse events reported from the combination of EnAd and Pxl were as previously described (for both agents individually), with ‘flu-like symptoms reported in the majority of patients following EnAd administration. Hematological changes including neutropenia, previously identified at higher doses of EnAd IV monotherapy, were reported at the dose level tested in this study population. Virus kinetics, cytokine and anti-virus antibody responses were consistent with previous results with EnAd. As of 03May19, Investigator-assessed ORR is 37.5% (6/16), with median DoR of 16 weeks (range 8-32). Reductions in CA125 broadly follow the pattern of tumor regression, with 36% (4/11) achieving response according to GCIG CA125 criteria. Disease control rate (RECIST CR, PR, SD) is 75% (12/16). To date, matched biopsies (N = 2) have been analysed for pharmacodynamic markers, providing preliminary evidence of increased CD8 T cell infiltration in on-treatment tumour biopsies.
Conclusions
The combination of EnAd and Pxl has manageable tolerability. Favorable disease control is noted in this recurrent platinum-resistant population, which is worthy of further investigation.
Clinical trial identification
2013-001276-38.
Editorial acknowledgement
Legal entity responsible for the study
PsiOxus Therapeutics Ltd.
Funding
PsiOxus Therapeutics Ltd.
Disclosure
R. Brown: Shareholder / Stockholder / Stock options, Full / Part-time employment: PsiOxus Therapeutics Ltds. D. Krige: Full / Part-time employment: PsiOxus Therapeutics Ltds. J. Bendall: Full / Part-time employment: PsiOxus Therapeutics Ltds. G. Di Genova: Full / Part-time employment: PsiOxus Therapeutics Ltds. H. McElwaine-Johnn: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: PsiOxus Therapeutics Ltds. All other authors have declared no conflicts of interest.
Resources from the same session
2786 - Development of a living organoid biobank derived from colorectal cancer patients: towards personalized medicine
Presenter: Federica Papaccio
Session: Poster Display session 2
Resources:
Abstract
3351 - Microsatellite Instability Detection in Colorectal Cancer: 44-Center Comparison between the Idylla MSI Assay and Routine Molecular and Immunohistochemistry Tests on Formalin-Fixed Paraffin-Embedded Tissue
Presenter: Xavier Matias-guiu
Session: Poster Display session 2
Resources:
Abstract
4901 - Expression profile of EPHB3 and its prognostic significance in colorectal cancer progression (Running head: Prognostic value of EPHB3 in colorectal cancers)
Presenter: Bogun Jang
Session: Poster Display session 2
Resources:
Abstract
5030 - A pan-ErbB family inhibitor, AF8c, promotes apoptosis by DR5/Nrf2 activation via ROS in colorectal cancer cells
Presenter: Soyeon Jeong
Session: Poster Display session 2
Resources:
Abstract
5053 - Frequent BRAF, GNAS and SMAD4 mutations identified in Colorectal Mucinous Carcinomas
Presenter: Sun Mi Lee
Session: Poster Display session 2
Resources:
Abstract
5220 - Impact of CCL4 knockout using CRISPR Cas-9 technology on colorectal tumor progression
Presenter: Roba Barakat
Session: Poster Display session 2
Resources:
Abstract
5330 - Independent clinical validation of a gene expression profile to predict benefit of 5-FU in metastatic colorectal cancer
Presenter: Ida Buhl
Session: Poster Display session 2
Resources:
Abstract
5515 - WRN mutated Colorectal Cancer (CRC) is characterized by a distinct molecular and immunological profile
Presenter: Andreas Seeber
Session: Poster Display session 2
Resources:
Abstract
5716 - Mutation analysis of B2M gene in colorectal cancer patients with microsatellite instability
Presenter: Ivana Kašubová
Session: Poster Display session 2
Resources:
Abstract
870 - Selective Wnt/β-catenin small-molecule inhibitor CWP232228 impairs tumor growth of colon cancer
Presenter: Jin Young Kim
Session: Poster Display session 2
Resources:
Abstract