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DC Field | Value | Language |
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dc.contributor.author | Frentzas S. | - |
dc.contributor.author | Ahern E.S. | - |
dc.contributor.author | Weickhardt A.J. | - |
dc.contributor.author | Haydon A.M. | - |
dc.contributor.author | De Souza P.L. | - |
dc.contributor.author | Powderly J.D. | - |
dc.contributor.author | Wyant T. | - |
dc.contributor.author | Tang J. | - |
dc.contributor.author | Richards L. | - |
dc.contributor.author | Knickerbocker A. | - |
dc.contributor.author | Amit I. | - |
dc.contributor.author | Ofran Y. | - |
dc.contributor.author | Vasselli J.R. | - |
dc.date.accessioned | 2025-01-06T02:50:43Z | - |
dc.date.available | 2025-01-06T02:50:43Z | - |
dc.date.copyright | 2023 | - |
dc.date.issued | 2024-11-11 | en |
dc.identifier.citation | Journal of Clinical Oncology. Conference: 2023 American Society of Clinical Oncology Annual Meeting, ASCO. Chicago, IL United States. 41(16 Supplement) (pp e14507), 2023. Date of Publication: June 2023. | - |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/52824 | - |
dc.description.abstract | Background: AU-007 is a computationally designedmAb that binds to 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 endogenous or exogenous IL-2 (aldesleukin) towards T effector and NK cell activation, while diminishing immunosuppressive Treg activation and vascular leak. Unique in the IL-2 field, AU-007 can redirect endogenous IL-2 generated from A/IL- 2 driven T effector cell expansion in vivo, converting a Treg-mediated autoinhibitory loop into an immune stimulating loop. A/IL-2 is expected to prolong the 85-minute T1/2 of IL-2, allowing endogenous IL-2 (as A/IL-2) or low dose aldesleukin to initiate an anti-tumor response. Method(s): This first-inhuman Phase 1 study consists of 3 dose escalation arms, each starting with one 1+2 cohort followed by 3+3 cohorts. Arm 1A evaluates escalating doses of monotherapy AU-007 (intravenous, every 2 weeks [Q2W]). Arm 1B evaluates AU-007 (Q2W) plus 1 loading dose of subcutaneous, low dose aldesleukin with the 1st AU-007 dose. The AU-007 dose will be fixed with escalating aldesleukin doses in sequential cohorts. Arm 1C evaluates AU-007 plus escalating doses of concomitant subcutaneous, low dose aldesleukin, bothQ2W. The dose-limiting toxicity (DLT) evaluation period is the first 28 days of the 1st cycle. Tumor assessments by computed tomography scan occur with each 8-week cycle. The AU- 007 and aldesleukin dose and schedule for Phase 2 expansion will be based on safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD). Result(s): As of 01 February 2023, 8 patients have been enrolled into the first 3 Cohorts of Arm 1A (0.5, 1.5, and 4.5 mg/kg AU-007). AU-007 was well tolerated with no DLTs and all treatment-related adverse events were Grade 1. These occurred in 3 patients, 1 at each dose level. The 4th Cohort of Arm 1A (9 mg/kg AU-007) and the 1st Cohort of Arm 1B (4.5 mg/kg AU-007 + 1 aldesleukin dose of 15,000 IU/kg) are now being evaluated. Three of 4 tumor evaluable patients had a best response of stable disease and 2 continue treatment. Two patients discontinued with objective progression and one with clinical progression. Initial PK data (0.5 and 1.5 mg/kg) demonstrate dose proportional AU-007 serum concentrations with typical characteristics of an IgG1 human mAb. All 7 patients with available PD data demonstrate overall decreasing Tregs (% change and absolute) and eosinophils, which both express the trimeric IL-2 receptor. Conclusion(s): AU- 007 monotherapy at doses up to 4.5 mg/kg Q2W is safe and well tolerated, with initial signs of immune modulation consistent with AU-007's mechanism of action. These findings warrant continued escalation and combination with aldesleukin. | - |
dc.relation.ispartof | Journal of Clinical Oncology | - |
dc.subject.mesh | antineoplastic activity | - |
dc.subject.mesh | cancer inhibition | - |
dc.subject.mesh | computer assisted tomography | - |
dc.subject.mesh | immunomodulation | - |
dc.subject.mesh | monotherapy | - |
dc.title | 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. | - |
dc.type | Conference Abstract | - |
dc.identifier.affiliation | Oncology | - |
dc.description.conferencename | 2023 American Society of Clinical Oncology Annual Meeting, ASCO | - |
dc.description.conferencelocation | Chicago, IL, United States | - |
dc.type.studyortrial | Clinical trial | - |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=https://dx.doi.org/10.1200/jco.2023.41.16_suppl.e14507 | - |
local.date.conferencestart | 2023-06-02 | - |
dc.identifier.institution | (Frentzas, Ahern, Weickhardt, Haydon, De Souza, Powderly, Wyant, Tang, Richards, Knickerbocker, Amit, Ofran, Vasselli) Medical Oncology, Monash Health, School of Medical and Health Sciences,Monash University, Melbourne, VIC, Australia; Monash Medical Centre, Southern Health, Clayton, QLD, Australia; Austin Health, Heidelberg, Australia; Alfred Hospital, Melbourn, VIC, Australia; 531 Kingsway, Miranda, Wollstonecraft, NSW, NSW, Australia; Carolina BioOncology Institute, Huntersville, NC; Biolojic Inc, Cambridge, MA; Aulos Bioscience, Larkspur, CA; Biolojic Design, Rehovot, Israel | - |
local.date.conferenceend | 2023-06-06 | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairetype | Conference Abstract | - |
crisitem.author.dept | Oncology | - |
Appears in Collections: | Conferences |
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