Abstract CT178: AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update

Abstract Background: AU-007 is a computationally designed mAb that binds interleukin-2 (IL-2) on its CD25 binding epitope. AU-007-bound IL-2 cannot bind trimeric (CD25, CD122, CD132) IL-2 receptors (IL-2R) on regulatory T cells (Tregs), vascular endothelium, or eosinophils, but IL-2’s binding to dimeric (CD122, CD132) IL-2R on effector T (T eff) and NK cells is unhindered. AU-007 thus redirects IL-2 towards T eff and NK cell activation, while diminishing Treg activation and vascular leak, and redirects IL-2 generated from T eff cell expansion, converting a Treg-mediated autoinhibitory loop into an immune stimulating loop. Methods: Phase 1 (Ph1) dose escalation consisted of 3 arms evaluating 19 tumor types. Arm 1A evaluated escalating doses (0.5 - 12 mg/kg) of AU-007 IV every 2 weeks (Q2W). Arm 1B evaluated 4.5 mg/kg AU-007 Q2W + escalating doses (15,000 [K] - 270K IU/kg) of one subcutaneous (SC) dose of aldesleukin administered on study day 1. Arm 1C evaluated escalating Q2W doses (4.5 - 12 mg/kg) of AU-007 and SC aldesleukin (15K - 270K IU/kg) Q2W. The ongoing Phase 2 (Ph2) cohort expansion evaluates the recommended Ph2 dose (RP2D) in patients with melanoma (mel), renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC) ± avelumab (data not reported) having protocol defined measurable disease at baseline. Results: As of 02 December 2024, 86 patients enrolled into the study. Ph1 is complete; AU-007 ± aldesleukin was well-tolerated with up to 11 cycles (21 months [M]) administered with no dose-limiting toxicity. Eight mel and 9 RCC patients have enrolled in Ph2 at the RP2D of 9 mg/kg AU-007 Q2W and 135K IU/kg single aldesleukin dose. Additionally, 2 mel patients received the B dose regimen in Ph1. Nine mel and 7 RCC patients had protocol-defined measurable lesions and were evaluable for objective response. Two mel patients refractory to anti-CTLA-4 and PD-1 therapy had tumor reductions of 48% (on treatment for 14 M) and 100% (ongoing at 10 M). A mel patient refractory to anti-PD-1 + relatlimab therapy had a 55% reduction (ongoing at 7 M). Three RCC patients had tumor reductions of 4, 13, and 23% (ongoing at 10 M). In Ph 1, a nasopharyngeal cancer patient had a confirmed PR (50%), and a bladder cancer patient with non-measurable disease had a metabolic complete response per PET; both patients are ongoing for over 20 M. A colon cancer patient had 26% tumor shrinkage through 2 cycles. The most common treatment-related adverse events (TRAEs) were Grade 1/ 2 fatigue (17%), chills (15%), pyrexia (15%), and infusion-related reaction (12%). The incidence of Grade 3/4 TRAEs and drug-related SAEs was 9% and 6%, respectively. All events resolved and no Grade 5 TRAE occurred. Conclusions: AU-007 + low-dose SC aldesleukin exhibits a manageable toxicity profile with promising efficacy and durability of activity across multiple tumor types. Ph 2 cohorts evaluating melanoma, RCC, and NSCLC are ongoing. Citation Format: Meredith McKean, Sophia Frentzas, Drew Rasco, John Powderly, Andrew Weickhardt, Alison Hiong, Paul de Souza, George Blumenschein, Vinod Ganju, Siwen Hu-Lieskovan, Ganessan Kichenadasse, Catherine Oakman, Nehal Lakhani, TImothy Wyant, Jenny Tang, Lori Richards, Aron Knickerbocker, Inbar Amit, Yanay Ofran, James Vasselli. AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin, in advanced solid tumors: Phase 2 update [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT178.