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
4413 - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF trial
Presenter: Ghassan Abou-Alfa
Session: Poster Display session 2
Resources:
Abstract
4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Lorenza Rimassa
Session: Poster Display session 2
Resources:
Abstract
5509 - A Randomized Controlled, Open label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine versus Gemcitabine alone in Patients with Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment (NCT03126435)
Presenter: Li-Tzong Chen
Session: Poster Display session 2
Resources:
Abstract
1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.
Presenter: Sylvie Lorenzen
Session: Poster Display session 2
Resources:
Abstract
2392 - GLOW: Randomized Phase 3 Study of Zolbetuximab + CAPOX Compared With Placebo + CAPOX as First-line Treatment of Patients With CLD18.2⁺/HER2⁻ Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Manish Shah
Session: Poster Display session 2
Resources:
Abstract
5217 - PRODIGE67_UCGI33 ARION: Association of Radiochemotherapy and Immunotherapy for the treatment of unresectable Oesophageal caNcer: a comparative randomized phase II trial
Presenter: Rosine Guimbaud
Session: Poster Display session 2
Resources:
Abstract
1726 - Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Presenter: Kenro Hirata
Session: Poster Display session 2
Resources:
Abstract
2279 - FRONTiER: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Presenter: Shun Yamamoto
Session: Poster Display session 2
Resources:
Abstract
4912 - A phase Ib/II study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined With mXELOX as First-line Therapy for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Jiafu Ji
Session: Poster Display session 2
Resources:
Abstract
3780 - Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Presenter: Salah-Eddin Al-Batran
Session: Poster Display session 2
Resources:
Abstract