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
3425 - Feasibility and impact of prospective DPYD screening in the Irish population
Presenter: Mohammed Zameer
Session: Poster Display session 2
Resources:
Abstract
1972 - Diet-derived metabolites and the risk of colorectal cancer: a nested case-control study in a population-based cohort, the Singapore Chinese Health Study
Presenter: Dawn Chong
Session: Poster Display session 2
Resources:
Abstract
4103 - Loss of subcutaneous adipose tissue during chemotherapy predicts reduced survival in patients with incurable colorectal cancer undergoing palliative therapy
Presenter: Erin Stella Sullivan
Session: Poster Display session 2
Resources:
Abstract
4309 - Obese and overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab.
Presenter: Bozena Cybulska-Stopa
Session: Poster Display session 2
Resources:
Abstract
3554 - Patient characteristics associated with poor performance status, ECOG 2-3, and effect on survival in 1086 Finnish metastatic colorectal cancers (mCRC) nationwide (prospective RAXO study)
Presenter: Pia Österlund
Session: Poster Display session 2
Resources:
Abstract
4572 - Discovery and Diagnosis of Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results from a European Survey
Presenter: Iga Rawicka
Session: Poster Display session 2
Resources:
Abstract
4783 - Adherence to recommended intake of calcium and colorectal cancer risk in the HEXA study
Presenter: Jeeyoo Lee
Session: Poster Display session 2
Resources:
Abstract
5106 - Body size, sex and sidedness of incident colorectal cancer in a prospective Swedish cohort study
Presenter: Christina Siesing
Session: Poster Display session 2
Resources:
Abstract
3364 - Middle East & North Africa Registry to characterize RAS mutation status and tumor specifications in recently diagnosed patients with metastatic colorectal cancer (MORE-RAS Study)
Presenter: Mohamed Oukkal
Session: Poster Display session 2
Resources:
Abstract
3668 - Patient Demographics and Management Landscape of Metastatic Colorectal Cancer in the Third Line Setting: real-world data in an Australian Population
Presenter: Sandy Tun Min
Session: Poster Display session 2
Resources:
Abstract