Article Text

Download PDFPDF

762 First-in-human phase 1a study of NG-641, a tumour-selective vector expressing a FAP-TAc bispecific antibody and immune enhancer module, in patients with metastatic/advanced epithelial tumours (STAR)
  1. George Simon1,
  2. Vivek Subbiah2,
  3. Lee Rosen3,
  4. Heinz-Josef Lenz4,
  5. Haeseong Park5,
  6. Minesh Patel6,
  7. David Miles6,
  8. Stephanie Wallis6,
  9. Vladimir Evilevitch6,
  10. David Krige6,
  11. Mark Powell6 and
  12. Tom Lillie6
  1. 1H Lee Moffitt Cancer Center, Tampa FL and Advent Health Research Institute, Celebration, Tampa, FL, USA
  2. 2MD Anderson Cancer Center, Houston, TX, USA
  3. 3UCLA Medical Center, Los Angeles, CA, USA
  4. 4USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  5. 5Washington University, St. Louis, MO, USA
  6. 6PsiOxus Therapeutics Ltd, Abingdon, Oxford, UK


Background NG-641 is a tumour-selective adenoviral vector that expresses a fibroblast activation protein-directed bi-specific T-cell activator antibody (FAP-TAc) and potent immune cell enhancers (CXCL9/CXCL10/IFNα). FAP-TAc targets killing of immunosuppressive cancer-associated fibroblasts, while immune enhancers recruit and activate immune cells (e.g. CD8+ T cells and dendritic cells). NG-641 is stable in the bloodstream and has low immunogenicity, allowing for IV delivery. We report first-in-human dose-escalation results for this novel immunotherapy.

Methods STAR (NCT04053283) is a Phase 1 study of NG-641 in patients with metastatic/advanced epithelial tumours and no standard treatments. The primary objective was safety and tolerability of IV NG-641 monotherapy (one cycle with single doses on Days 1, 3 and 5; five increasing dose levels). Preliminary anti-tumour activity was a secondary objective.

Results As of June 2022, 20 heavily pre-treated patients (median 60 years; 55% male) with metastatic/advanced epithelial tumours (35% colorectal; 15% pancreatic; 10% liver) received NG-641. DLTs of hypertension and dyspnoea occurred in one patient at Dose Level [DL] 2. The first patient at DL5 (1×1012 vp on Day 1 and 1×1013 vp on Days 3 and 5) experienced a DLT of Grade 3 CRS following an innate response to viral particles. The NG-641 MTD was thus determined to be 6×1012 vp as part of a “low-high-high” dosing regimen. Overall, the NG-641 safety profile was consistent with acute reactions to viral particles, with no evidence of transgene-related toxicity (table 1). Dose-dependent, specific and sustained increases in serum IL-12, IFNγ and IL-17a were detected from ~Wk2-12 (last measurement). Similar elevations did not occur with the unarmed parent vector, suggesting a transgene driven effect. No systemic FAP-TAc transgene protein was detected at any dose level indicating a lack of spill over from tumour into systemic circulation. Among evaluable patients, increases in tumour CD8+ T-cell infiltration were seen in 3/7 patients, including one patient with pancreatic cancer and one with colorectal cancer. No objective responses occurred but 2/3 patients at DL3 had stable disease (DL4 under assessment).

Conclusions NG-641 demonstrated manageable tolerability, with no evidence of systemic transgene-related toxicity. The MTD of NG-641 was 6×1012 vp when given in a “low-high-high” dosing regimen. Consistent with the encoded immunostimulatory transgenes, NG-641 led to specific and sustained cytokine responses, without systemic spill over of transgene products from the tumour microenvironment. These results suggest that NG-641 drives local immunological tumour changes without systemic toxicity. A further trial (NEBULA, NCT05043714) examining NG-641 with nivolumab is ongoing.

Acknowledgements This study was funded by PsiOxus Therapeutics Limited. Medical writing support: Sandra Borkowska-Heurtaux, PhD, of PsiOxus Therapeutics Limited.

Trial Registration NCT number: NCT04053283

Ethics Approval This study was approved by

UT MD Anderson Cancer Center IRB (Protocol 2019-0636)

UCLA Institutional Review Board (IRB#21-000275)

University of Southern California Institutional Review Board (Proposal #HS-19-00696)

Ochsner Health System Institutional BioSafety Committee (Protocol 2019.02)

WIRB/Wcg IRB (Tracking number 20190830; Washington University in St. Louis; Moffitt – Advent Health)

Consent All patients provided informed consent before taking part in this study.

Abstract 762 Table 1

Safety of NG-641 monotherapy (Dose Levels 1–4)

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.