Imperial College London
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ProfessorIainMcNeish

Faculty of Medicine, Department of Surgery & Cancer

Chair in Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2185i.mcneish Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

G036Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{McNeish:2021:10.1136/jitc-2021-003645,
author = {McNeish, I},
doi = {10.1136/jitc-2021-003645},
journal = {Journal for ImmunoTherapy of Cancer},
pages = {1--14},
title = {Safety and efficacy of the tumour-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: a phase 1 clinical trial},
url = {http://dx.doi.org/10.1136/jitc-2021-003645},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background Treatment outcomes remain poor in recurrent platinum-resistant ovarian cancer. Enadenotucirev, a tumor-selective and blood stable adenoviral vector, has demonstrated a manageable safety profile in phase 1 studies in epithelial solid tumors.Methods We conducted a multicenter, open-label, phase 1 dose-escalation and dose-expansion study (OCTAVE) to assess enadenotucirev plus paclitaxel in patients with platinum-resistant epithelial ovarian cancer. During phase 1a, the maximum tolerated dose of intraperitoneally administered enadenotucirev monotherapy (three doses; days 1, 8 and 15) was assessed using a 3+3 dose-escalation model. Phase 1b included a dose-escalation and an intravenous dosing dose-expansion phase assessing enadenotucirev plus paclitaxel. For phase 1a/b, the primary objective was to determine the maximum tolerated dose of enadenotucirev (with paclitaxel in phase 1b). In the dose-expansion phase, the primary endpoint was progression-free survival (PFS). Additional endpoints included response rate and T-cell infiltration.Results Overall, 38 heavily pretreated patients were enrolled and treated. No dose-limiting toxicities were observed at any doses. However, frequent catheter complications led to the discontinuation of intraperitoneal dosing during phase 1b. Intravenous enadenotucirev (1×1012 viral particles; days 1, 3 and 5 every 28-days for two cycles) plus paclitaxel (80 mg/m2; days 9, 16 and 23 of each cycle) was thus selected for dose-expansion. Overall, 24/38 (63%) patients experienced at least 1 Grade ≥3 treatment-emergent adverse event (TEAE); most frequently neutropenia (21%). Six patients discontinued treatment due to TEAEs, including one patient due to a grade 2 treatment-emergent serious AE of catheter site infection (intraperitoneal enadenotucirev monotherapy). Among the 20 patients who received intravenous enadenotucirev plus paclitaxel, 4-month PFS rate was 64% (median 6.2 months), objective response rate was
AU  - McNeish,I
DO  - 10.1136/jitc-2021-003645
EP  - 14
PY  - 2021///
SN  - 2051-1426
SP  - 1
TI  - Safety and efficacy of the tumour-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: a phase 1 clinical trial
T2  - Journal for ImmunoTherapy of Cancer
UR  - http://dx.doi.org/10.1136/jitc-2021-003645
UR  - https://jitc.bmj.com/content/9/12/e003645
UR  - http://hdl.handle.net/10044/1/93119
VL  - 9
ER  -
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