AU-007 Demonstrates Safety and Efficacy in Heavily Pretreated Solid Tumors

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Treatment with AU-007, an interleukin-2 (IL-2)–binding monoclonal antibody, administered alone or in combination with low-dose subcutaneous aldesleukin (Proleukin), demonstrated a tolerable safety profile and signs of antitumor activity in heavily pretreated patients with advanced tumors, according to updated findings from a phase 2 study (NCT05267626) presented at the 2025 AACR Annual Meeting.

AU-007 and aldesleukin appeared to be well tolerated up to 11 cycles (21 months). Two patients with melanoma who were refractory to anti–CTLA-4 and PD-1 therapy had tumor reductions of 48% after 14 months and 100% at 10 months, respectively. One patient with melanoma refractory to anti–PD-1 therapy and relatlimab had a 55% reduction at 7 months. In 3 patients with renal cell carcinoma (RCC), there were tumor reductions of 4%, 13%, and 23% at 10 months. Additionally, a patient with colon cancer had a 26% tumor shrinkage after 2 cycles.

Two case reports from the phase 1 dose escalation portion were also presented in the poster. The first was of a 67-year-old male patient with metastatic bladder cancer who progressed on anti–PD-L1 therapy in March 2023, with 2 lesions that had strong PET scan-positivity at baseline. In April 2023, an initial dose of AU-007 at 4.5 mg/kg plus 45,000 IU/kg aldesleukin was administered. In March 2024, PET imaging of the lesions was negative, and the response was considered an ongoing metabolic complete response (CR) for 1 year. At the time of the presentation, this patient continued receiving treatment and was tolerating it well, with only grade 1 toxicity observed.

The second case report was of a 55-year-old male patient with metastatic nasopharyngeal head and neck cancer (HNC) who progressed on 5 prior systemic therapies, including platinum-based chemotherapy and nivolumab (Opdivo). In August 2023, an initial dose of AU-007 and aldesleukin was administered, and the AU-007 dose was increased to 9 mg/kg after 4 months. At the end of cycle 10 (20 months), the patient’s lesion had resolved, and there was only grade 1 drug-related toxicity observed through the treatment course.

According to investigators, AU-007 has a unique pharmacodynamic profile in the IL-2 therapeutic class; AU-007’s mechanism is to redirect IL-2 to effector T cells and natural killer cells and away from regulatory T cells (Tregs) while completely inhibit binding to CD25 without inhibiting binding to CD122 or CD123. The decrease in Tregs “appears to be [a] critical determinant of observed efficacy,” as stated in the poster presented at the meeting.

About the Phase 2 Study of AU-007

AU-007 is being investigated in a phase 1/2 open-label, dose-escalation and -expansion study. Phase 1, which evaluated AU-007 as a monotherapy, with a single loading dose of aldesleukin and with aldesleukin given every 2 weeks, is complete. Investigators are currently assessing for the recommended phase 2 dose.

Efficacy is based on the pharmacodynamic markers of immune stimulation and objective response rates. Tumors are assessed at the end of each 8-week cycle.

Patient Characteristics

A total of 95 patients were include in the analysis. The mean age was 64.3 years old (range, 33-89), 53 patients were male (56%), 84 were White (88%), 4 were Black (4%), 4 were Asian (4%), 1 was American Indian/Alaska native (1%), and 2 were classed as other (2%). Forty percent of patients had an ECOG performance status of 0, while 60% had a status of 1. The mean number of prior therapies was 3.1 (range, 1-10). The most common tumor histologies were melanoma (n = 29), clear cell RCC (n = 19), and non–small cell lung cancer (NSCLC; n = 12).

Safety and Tolerability

In patients who received AU-007 monotherapy (n = 15), 14 patients (93%) experienced any-grade adverse events (AEs). Drug-related AEs were reported in 4 patients (27%), but there were no serious drug-related AEs or drug-related grade 3 or 4 AEs.

In the combination arm (n = 75), 69 patients (92%) experienced AEs, and 56 patients (75%) experienced drug-related AEs. Serious drug-related AEs included cytokine release syndrome (CRS; n = 3), infusion-related reaction (n = 1), and fever (n = 1). Drug-related grade 3 or 4 AEs included lymphopenia (n = 6), CRS, anemia, lipase elevation, neutropenia, and maculopapular rash (each n = 1).

The most common grade 1 or 2 AEs that occurred in at least 5% of patients in the combination arm were fatigue (21%), pyrexia (21%), chills (19%), infusion-related reaction (15%), nausea (13%), injection site reaction (11%), injection site erythema (8%), CRS (8%), aspartate aminotransferase elevation (7%), headache (7%), influenza-like illness (7%), anemia (5%), and alanine transaminase elevation (5%). The grade 3 or 4 toxicities in 5% or more patients were lymphopenia (8%), anemia (3%), and CRS (1%).

No dose-limiting toxicities were reported.

Looking Ahead

Phase 2 expansion cohorts are evaluating AU-007 and aldesleukin in patients with cutaneous melanoma and NSCLC. One expansion cohort in patients with NSCLC is investigating AU-007 and aldesleukin with avelumab (Bavencio). Another expansion cohort will enroll patients with cutaneous melanoma who have not been treated with a BRAF/MEK inhibitor. Here, patients will receive AU-007 with a single dose of aldesleukin plus nivolumab as a second-line treatment.

Reference:

McKean M, Frentzas S, Rasco D, et al. 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. Presented at: American Association for Cancer Research Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract CT178.