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717 A phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors: interim results from dose escalation
  1. Sophia Frentzas1,
  2. Elizabeth Ahern2,
  3. Andrew Weickhardt3,
  4. Andrew Haydon4,
  5. John Powderly5,
  6. Drew Rasco6,
  7. Meredith McKean7,
  8. Paul de Souza8,
  9. Timothy Wyant9,
  10. Jenny Tang10,
  11. Lori Richards10,
  12. Aron Knickerbocker10,
  13. Inbar Amit11,
  14. Yanay Ofran11 and
  15. James Vasselli12
  1. 1Monash Medical Centre, Clayton, VIC, Australia
  2. 2Monash Health, Monash University, Clayton, Australia
  3. 3Olivia Newton-John Cancer Research Inst., Heidelberg, VIC, Australia
  4. 4Alfred Hopital, Melbourne, VIC, Australia
  5. 5Carolina BioOncology Institute, Huntersville, NC, USA
  6. 6START, San Antonio, TX, USA
  7. 7Sarah Cannon Research Institute, Nashvlle, TX, USA
  8. 8University of Western Sydney, Sydney, NSW, Australia
  9. 9Biolojic inc, Cambridge, MA, USA
  10. 10Aulos Bioscience, Larkspur, CA, USA
  11. 11Biolojic Design, Rehovot, Israel
  12. 12Aulos Bioscience, San Francisco, CA, USA


Background AU-007 is a computationally designed mAb that binds IL-2 on its CD25 binding epitope. AU-007 bound IL-2 (A/IL-2) cannot bind to trimeric (CD25, CD122, CD132) IL-2 receptors (IL-2R) on Tregs, vascular endothelium, or eosinophils, but IL-2’s binding to dimeric IL-2Rs (CD122, CD132) on T effector and NK cells is unhindered. AU-007 thus redirects IL-2 towards T effector and NK cell activation, while diminishing Treg activation and vascular leak. Unique among IL-2 therapeutics, AU-007 redirects IL-2 generated from T effector cell expansion, converting a Treg-mediated autoinhibitory loop into an immune stimulating loop.

Methods This Phase 1 study (NCT05267626) consists of 3 dose escalation arms. Arm 1A evaluates escalating doses of AU-007 (intravenous, every 2 weeks [Q2W]). Arm 1B evaluates AU-007 (Q2W) plus one low-dose aldesleukin subcutaneous injection. The AU-007 dose is fixed with escalating aldesleukin doses in sequential cohorts. Arm 1C evaluates AU-007 plus escalating doses of concomitant low-dose subcutaneous aldesleukin, both Q2W. Tumor assessments occur with each 8-week cycle.

Results As of 15 June 2023, 24 patients have received AU-007 +/- aldesleukin, 13 in Arm 1A, 6 in Arm 1B, and 5 in Arm 1C. AU-007 (+/- aldesleukin) was well-tolerated, with no DLTs, at doses up to 9 mg/kg of AU-007 alone, 4.5 mg/kg + one 45,000 IU/kg aldesleukin dose, and 4.5 mg/kg + 15,000 IU/kg aldesleukin Q2W. Two patients had transient lymphopenia (Grade 3 and 4); all other treatment-related adverse events were Grade 1 or 2 with the most common (> 10%) being fatigue (30%), nausea (17%), and chills (12%). Serum Tregs and eosinophils (both express trimeric IL-2Rs) decreased in patients across all cohorts while NK and CD8 cell serum concentrations trended upwards. The CD8 to Treg ratio continues to trend upward in patients across each study arm. Of the response evaluable patients, a best response of stable disease occurred in 4 patients on Arm 1A (including a 15% target lesion decrease in a patient with non-small cell lung cancer who progressed on chemo+anti-PD-L1), and 1 melanoma patient on Arm 1B who progressed on anti-CTLA-4 + anti-PD-1 therapy, with a 25% tumor target lesion decrease. AU-007 PK demonstrates dose proportional increases in serum concentrations and no evidence of ADA.

Conclusions AU-007 +/- aldesleukin reduces serum Tregs and increases NK and CD8 cells, consistent with AU-007’s mechanism of action. The mild toxicity, pharmacodynamic and early objective efficacy findings in heavily pretreated patients warrant continued escalation of AU-007 +/- aldesleukin.

Trial Registration NCT05267626

Ethics Approval The study obtained ethics approval/institutional review board approval and participants gave informed consent before taking part.

Australia Ethics Committee:

Monash Health; Monash Health Reference: RES-21–0000-722A; 15 Mar 2022


Advarra IRB Approval SSU0019174; 29 Jul 2022

Salus IRB Approval 14 Feb 2023

Castle IRB Approval 22 Mar 2023

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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