Abstract 2518
Background
Enadenotucirev (EnAd) is a tumor-selective chimeric Ad11/Ad3 group B oncolytic adenovirus. Following IV dosing of EnAd, viral delivery has been shown in various carcinomas together with CD8+ T-cells. These data provide a rationale for combination of EnAd with nivolumab (anti-PD-1).
Methods
EnAd was escalated in patients with metastatic epithelial tumors in a 3 + 3 design. Subjects received increasing dose levels and/or cycles of EnAd followed by up to 8 cycles of nivolumab. The primary objective of the dose escalation phase was to evaluate safety and recommend a dose for expansion. Secondary endpoints include ORR and OS.
Results
31 patients with metastatic colorectal cancer (mCRC), with median 4 prior lines of therapy, were treated. Of these, 22 are confirmed MSS. EnAd dosing ranged between 1x1012 and 3x1012 virus particles infused IV 3 times weekly for one or two weeks, followed by nivolumab. Flu-like symptoms were reported in the majority of patients following EnAd administration. Adverse events of infusion reaction and hypoxia meeting DLT criteria were reported on C2D1 administration of EnAd requiring increased prophylaxis. Grade 4 acute renal injury was reported in one subject, with renal biopsy showing membranoproliferative glomerulonephritis (GN) indicative of immune complex deposition. Additional monitoring revealed changes suggestive of post-infectious GN in ∼25% of patients after 3-4 weeks of EnAd dosing. These were asymptomatic and resolved without treatment. Kinetics, cytokines and anti-drug antibody responses were consistent with known profiles for both agents. As of 03May2019, median OS is reported as 12.6 mo and median PFS is 2.8 mo. There were no objective responses, but PD markers in 6/8 matched biopsy samples show evidence of increased CD8 T cell infiltration and upregulation of markers of T cell activation. Stable disease exceeding 4 mo was seen in 6/31 (4/22 MSS).
Conclusions
The combination of EnAd and nivolumab has a manageable toxicity profile supporting further investigation in study expansion. Favourable OS outcome in a highly refractory CRC population was noted and may suggest delayed immune antitumor activity in this population.
Clinical trial identification
2017-001231-39.
Editorial acknowledgement
Legal entity responsible for the study
PsiOxus Therapeutics Ltd.
Funding
PsiOxus Therapeutics Ltd; Bristol-Myers Squibb.
Disclosure
P. Basciano: Full / Part-time employment: Bristol-Myers Squibb. R. Brown: Shareholder / Stockholder / Stock options, Full / Part-time employment: PsiOxus Therapeutics Ltds. O. Arogundade: Full / Part-time employment: PsiOxus Therapeutics Ltds. C. Cox: Full / Part-time employment: PsiOxus Therapeutics Ltds. G. Di Genova: Full / Part-time employment: PsiOxus Therapeutics Ltds. D. Krige: 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
5747 - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
Presenter: Fanny Preat
Session: Poster Display session 2
Resources:
Abstract
1837 - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
Presenter: Kenjiro Jimbo
Session: Poster Display session 2
Resources:
Abstract
4347 - Pneumonitis and fibrosis after breast cancer radiation.
Presenter: Jarle Karlsen
Session: Poster Display session 2
Resources:
Abstract
2280 - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: a nationwide study in Korean Breast Cancer Society
Presenter: Sungmin Park
Session: Poster Display session 2
Resources:
Abstract
804 - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer
Presenter: Chang-ik Yoon
Session: Poster Display session 2
Resources:
Abstract
2701 - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe
Presenter: Francesco Giusti
Session: Poster Display session 2
Resources:
Abstract
1437 - A critical appraisal of quality indicators of breast cancer treatment in Belgium
Presenter: Didier Verhoeven
Session: Poster Display session 2
Resources:
Abstract
1534 - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
Presenter: Phillip Blanchette
Session: Poster Display session 2
Resources:
Abstract
4363 - Evaluation of endocrine therapy and patients preferences in early breast cancer: results of Elena study
Presenter: Emilia Montagna
Session: Poster Display session 2
Resources:
Abstract
2679 - Baseline Quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): the French multicentric prospective CANTO cohort study
Presenter: Idlir Licaj
Session: Poster Display session 2
Resources:
Abstract