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
1988 - Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Presenter: Semir Vranic
Session: Poster Display session 2
Resources:
Abstract
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract