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
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome
Presenter: Valentina Fanotto
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract
1452 - RBP-Jκ in colon cancer cells facilitates tumor associated macrophages (TAMs)-induced cell metastasis by secreting CXCL11
Presenter: Meng jie Liu
Session: Poster Display session 2
Resources:
Abstract