AU-007 Combo Dosing Begins in Melanoma Phase 2 Trial With Opdivo

The first patient has been dosed with AU-007 in a phase 2 cohort evaluating the drug in combination with the anti-PD-1 antibody Opdivo (nivolumab) and low-dose, subcutaneous aldesleukin for second-line treatment of melanoma, according to a news release from the drug’s manufacturer, Aulos Bioscience.

“We are excited that the first patient is receiving treatment in this new phase 2 cohort evaluating AU-007 in combination with Opdivo,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer, in the news release. “Given its unique mechanism of action and the positive data presented to date on AU-007 and low-dose, subcutaneous aldesleukin, we believe that AU-007 holds real promise as a novel immuno-oncology treatment in combination with checkpoint inhibitors in multiple cancer types. These include non-small cell lung cancer, for which we initiated a phase 2 cohort with the anti-PD-L1 antibody [Bavencio (avelumab)] in November, and now melanoma.”

An additional phase 2 cohort in melanoma will allow the Opdivo combination portion of the study to move forward, according to the release. Preliminary data, presented in November at the Society for Immunotherapy of Cancer 39th Annual Meeting, showed that AU-007 plus low-dose, subcutaneous aldesleukin was clinically active in patients with melanoma, with durable objective responses reported.

Previous Phase 1/2 trial

In previous findings from the phase 1 dose-escalation cohorts of the phase 1/2 trial, AU-007 was well tolerated and showed early signs of antitumor activity when used alone or in combination with low-dose, subcutaneous aldesleukin across multiple solid tumors.

Data presented at the 38th Society for Immunotherapy of Cancer Annual Meeting included 42 patients who received AU-007 alone or with aldesleukin as of Oct. 13, 2023.

Among heavily pretreated patients with melanoma, renal cell carcinoma and non–small cell lung cancer — including those whose disease progressed on prior checkpoint inhibitors — AU-007 showed early efficacy and a manageable safety profile. No dose-limiting toxicities, pulmonary or generalized edema, or vascular leakage were observed.

Of the 33 tumor-evaluable patients in the dose-escalation cohorts, nine (27%) achieved stable disease as their best response, and 16 remained on treatment at the data cutoff.

Notably, one patient with melanoma who had not responded to prior anti-CTLA-4 and anti-PD-1 therapies experienced a 40% reduction in target tumor lesions, with shrinkage observed as early as week 8 and continuing through weeks 16 and 24. Another patient with renal cell carcinoma, whose disease had progressed through anti-PD-1 therapy, had a 20% reduction in target lesions starting at week 8. Both patients remained on study at the time of reporting.

Most treatment-related side effects were grade 1 (mild) or 2 (moderate). Three cases of transient grade 3 (severe) or 4 (life-threatening) lymphopenias were reported but were not associated with adverse outcomes. No patients discontinued treatment due to drug-related side effects.

More About AU-007

AU-007, the first human monoclonal antibody designed with artificial intelligence to enter a clinical trial, targets interleukin-2 (IL-2) to enhance anti-tumor immune responses.

Unlike other IL-2-based therapies, AU-007 blocks IL-2 — whether naturally occurring or administered — from binding to suppressive immune cells, while preserving its ability to stimulate immune-activating cells. This mechanism may reduce side effects such as vascular leak syndrome and pulmonary edema that are commonly seen with high-dose IL-2 treatment, as per the release.

Aulos plans to present preliminary data in the second half of 2025 from a phase 2 cohort evaluating AU-007 with Opdivo and low-dose, subcutaneous aldesleukin as a second-line treatment for melanoma. The company will also share new phase 2 data on AU-007 and low-dose, subcutaneous aldesleukin without a checkpoint inhibitor later this month at the American Association for Cancer Research Annual Meeting.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.