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AU-007 is well-tolerated and shows early evidence of antitumor activity when used as a monotherapy or in combination with low-dose, subcutaneous aldesleukin across various solid tumors, according to preliminary data from the phase 1 dose-escalation cohorts of the phase 1/2 trial of the agent.¹

Findings presented at the 38th Society for Immunotherapy of Cancer Annual Meeting were from 42 patients who received AU-007 as of October 13, 2023, alone or in combination with aldesleukin. Patients in arm 1A were treated with AU-007 as a monotherapy with treatment up to 12 mg/kg, arm 1B was treated with 4.5 mg/kg of AU-007 and escalating aldesleukin once on day 1, and arm 1C received 4.5 mg/kg of AU-007 in combination with aldesleukin given every 2 weeks.

Among heavily pre-treated patients with melanoma, renal cell carcinoma (RCC), and non–small cell lung cancer (NSCLC), including patients whose tumors progressed through checkpoint inhibitors, AU-007 demonstrated promising early efficacy and safety data with no pulmonary or generalized edema, vascular leakage, or dose-limiting toxicity (DLT) observed.

Additional findings from the study showed that across the phase 1 dose-escalation cohorts, 9 of 33 (27%) tumor-evaluable patients had a best response of stable disease. Sixteen patients continue treatment as of the data cutoff date.

Looking at the CT scans of a patient with melanoma who had progressed on anti-CTLA-4 and anti-PD-1 therapy without a response, there was a 40% decrease in target tumor lesions seen, and there was tumor shrinkage observed starting at 8 weeks which shrank further at weeks 16 and 24. This patient continues on with the study.

In a second patient with RCC whose tumors had progressed through prior anti-PD-1 therapy, scans showed that there was a 20% shrinkage in target tumor lesions beginning at 8 weeks. This patient also continues on with the study.

For safety, with the exception of 3 transient grade 3 or 4 lymphopenia, all drug-related adverse events (AEs) were grade 1 or 2. The 3 grade 3/4 lymphopenia were not associated with adverse outcomes in patients receiving AU-007 and aldesleukin.

Additionally, no patients discontinued treatment due to a drug-related AE, and no DLTs were observed.

About AU-007 and the Phase 1/2 Study

AU-007 is the first human IgG1 monoclonal antibody designed using artificial intelligence. The agent prevents IL-2 from binding to high-affinity IL-2 receptors on regulatory T cells, vasculature, pulmonary tissue, and eosinophils. Further, AU-007 redirects IL-2 to medium-affinity receptors on effector T cells and natural killer cells.¹

In the 2-part, open-label, first-in-human, phase 1/2 trial of AU-007, investigators continue to evaluate the safety, tolerability, immunogenicity, and clinical activity of the agent in patients with unresectable locally advanced or metastatic cancer. Patients are being enrolled at multiple locations in the United States and Australia.²

Patients 18 years and older are eligible for enrollment in the study if they have measurable or non-measurable disease as per RECIST v1.1 criteria. In the dose-escalation portion, patients must have selected tumor types and have progressed after standard of care treatment, be intolerant to treatment, or refused standard treatment. If patients have symptomatic central nervous system (CNS) metastases, they must have been treated and be asymptomatic for ≥ 14 days. Additionally, patients must have had no concurrent treatment for CNS disease and no concurrent leptomeningeal disease or cord compression.

Those who have been treated with a prior immune checkpoint inhibitor before enrollment must have checkpoint inhibitor immune-related toxicity resolved to either grade ≤ 1 or baseline to be eligible for enrollment. Further, if patients experienced previous checkpoint inhibitor-related hypothyroidism, they will be eligible for the study regardless of CTCAE grade resolution if well controlled on thyroid hormone replacement therapy.

The primary end points of the trial are safety, tolerability, and frequency of DLTs. Secondary end points include pharmacokinetics, and antitumor activity of AU-007 alone or with aldesleukin.

This study plans to transition to the phase 2 portion by late 2023 or early 2024. Phase 2 dose-expansion cohorts are planned in melanoma, RCC, and NSCLC.

REFERENCES:

1. New phase 1 dose escalation data show well-tolerated safety profile and anti-tumor activity for Aulos Bioscience’s AU-007 at society for immunotherapy of cancer (SITC) annual meeting. News release. Aulos Bioscience. November 3, 2023. Accessed November 7, 2023. https://tinyurl.com/mrwzc764

2. Study of AU-007, a monoclonal antibody that binds to IL-2 and inhibits IL-2Rα binding, in patients with unresectable locally advanced or metastatic cancer. ClinicalTrials.gov. Updated August 29, 2023. Updated November 7, 2023. https://clinicaltrials.gov/study/NCT05267626?tab=table