Aulos Bioscience has commenced a Phase 2 clinical trial evaluating the combination of AU-007, avelumab, and low-dose, subcutaneous aldesleukin in patients with PD-L1+ non-small cell lung cancer (NSCLC). The first patient has been dosed in this cohort, marking a significant step in the development of a potential new treatment option for patients who have progressed following first-line checkpoint inhibitor therapy.
The Phase 2 cohort is part of an ongoing Phase 1/2 clinical trial (NCT05267626) and is being conducted in collaboration with Ares Trading S.A., a Swiss subsidiary of Merck KGaA, Darmstadt, Germany. The study aims to assess the efficacy and safety of AU-007 in combination with avelumab (Bavencio), a human anti-programmed death ligand-1 (PD-L1) antibody, and low-dose aldesleukin, an interleukin-2 (IL-2) therapy.
Rationale for the Combination Therapy
The rationale behind this combination lies in the synergistic potential of the three agents. Avelumab is an approved PD-L1 inhibitor known for its ability to engage natural killer (NK) cells to kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC), while also blocking the PD-1/PD-L1 pathway that inhibits effector T cell (Teff) function. AU-007, a human IgG1 monoclonal antibody designed using artificial intelligence, is highly selective for the CD25-binding portion of IL-2, redirecting IL-2 to reinforce anti-tumor immune effects by preventing IL-2 from binding to regulatory T cells (Tregs) and promoting the expansion of effector T cells and NK cells. Low-dose aldesleukin provides additional IL-2 support to further stimulate the immune response.
Preclinical Evidence
Preclinical studies have demonstrated that the combination of AU-007 with a single loading dose of human IL-2 and an anti-PD-L1 surrogate of avelumab resulted in strong anti-cancer activity, including complete tumor eradication. These encouraging results prompted the evaluation of this combination in a clinical setting.
Clinical Trial Design and Patient Population
The Phase 1/2 study is currently enrolling patients with unresectable locally advanced or metastatic cancer at multiple clinical trial sites in the United States and Australia. The Phase 2 cohort specifically focuses on patients with PD-L1+ NSCLC who have experienced disease progression following first-line therapy with a checkpoint inhibitor. Aulos Bioscience plans to share preliminary data from this Phase 2 cohort in the first half of 2025.
Prior Data and Future Expectations
Previously presented data from the Phase 1 portion of the trial, at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, showed AU-007 and low-dose aldesleukin to be clinically active in tackling melanoma. The data also revealed durable Treg reduction, which correlated with progression-free survival.
Aron Knickerbocker, CEO of Aulos Bioscience, stated, "Avelumab’s profile, coupled with AU-007 and low-dose, subcutaneous aldesleukin, could potentially offer a new therapeutic option for patients with advanced or metastatic PD-L1+ non-small cell lung cancer that has progressed following first-line therapy with a checkpoint inhibitor."
