Imneskibart Plus Aldesleukin Yield Antitumor Activity in Melanoma and NSCLC

Data from an ongoing phase 1/2 clinical trial (NCT05267626) show that the combination of imneskibart (AU-007) and low-dose subcutaneous aldesleukin (IL-2) yields significant and durable antitumor activity in patients with checkpoint inhibitor–refractory melanoma and non–small cell lung cancer (NSCLC).¹

The findings were presented at the 2025 Society for Immunotherapy of Cancer Annual Meeting. As of the cutoff date of September 29, 2025, antitumor activity was assessed in 93 patients across multiple cancer types.

Patients with checkpoint inhibitor–refractory melanoma who progressed after receiving the doublet checkpoint inhibitor therapy of imneskibart plus aldesleukin showed deep and durable tumor reductions. Of 14 patients treated, 6 remain on treatment. Of these patients, 3 had the most significant tumor reductions beyond 1 year of treatment: 1 with a 48% reduction (on study for 14 months), 1 with a 58% reduction (on study for 18+ months), and 1 who achieved a complete response (CR; 100%; on study for 21+ months).

Five patients with checkpoint inhibitor–refractory melanoma were treated with the triplet combination of imneskibart, aldesleukin, and nivolumab (Opdivo). Early data from this treatment set show initial signs of antitumor activity in patients who progressed on prior doublet checkpoint inhibitors. A safety run-in with a lower dose of aldesleukin (45,000 IU/kg) was completed with no dose-limiting toxicities. This cohort is now enrolling patients at the full recommended phase 2 dose (RP2D) of aldesleukin (135,000 IU/kg). Of the 5 patients treated, 3 remain on treatment.

In patients with NSCLC who had failed prior checkpoint inhibitor therapy with or without chemotherapy, an early but clear signal of activity was observed.

Imneskibart, aldesleukin, and avelumab (Bavencio) were given to 9 patients with NSCLC, 4 of whom experienced tumor reductions. Of these patients, 2 who progressed on prior PD-1–targeted treatments experienced 43% and 48% reductions, respectively. Of the 2 patients, 1 continues on treatment.

Notably, 1 patient, a woman aged 68 years with adenocarcinoma who had progressed on 2 prior lines of therapy, began treatment with the avelumab combination. After 8 weeks of therapy, a 43% decrease in target lesion size was observed, and she continued into the next cycle.

In patients with other solid tumors and cancers, some long-lasting responses were reported. A patient with bladder cancer who progressed on anti–PD-L1 therapy has an ongoing confirmed metabolic CR and tests negative for circulating tumor DNA. This patient has been on treatment for nearly 3 years (32.5+ months). A patient with nasopharyngeal cancer who had progressed on 5 prior systemic therapies achieved a confirmed CR and has been on treatment for over 2 years (28.5+ months).

Safety Findings of the Trial

A mild and manageable safety profile was observed across all cohorts in phases 1 and 2. Most drug-related adverse events (AEs) were grade 1/2. The rate of grade 3/4 AEs remained low with mature data and was not increased by the addition of avelumab or nivolumab. The most common grade 3/4 AE was transient lymphopenia, a known effect of aldesleukin that causes lymphocyte redistribution.

In the imneskibart plus aldesleukin group (n = 77), 93% of patients experienced AEs. In both the avelumab (n = 11) and nivolumab (n = 5) combinations, 100% of patients experienced AEs. The most common AEs across the imneskibart plus aldesleukin arm, avelumab combination arm, and nivolumab combination arm were pyrexia (25% vs 18% vs 0%) respectively, fatigue (22% vs 18% vs 0%), and chills (21% vs 36% vs 20%).²

Notably, 1 patient experienced grade 4 cytokine release syndrome, which was resolved with standard care. It was retrospectively observed that the patient had subclinical elevated IL-6 levels at baseline, likely due to active gout.

It was observed that treatment with imneskibart plus aldesleukin leads to a continued decrease in the absolute cell counts of peripheral blood T cells (Tregs). The addition of nivolumab in the safety run-in did not negatively affect this reduction. A higher peripheral blood CD8/Treg ratio was directly associated with better clinical outcomes in patients with melanoma.

“Today’s data provide the most compelling support yet for our long-held view that imneskibart is clearly differentiated and has unmatched competitive advantages within the IL-2 class,” said Aron Knickerbocker, president and CEO of Aulos Bioscience, sponsor of the study, in a news release.¹ “We’re now seeing its ability to achieve deep and durable tumor shrinkages by expanding effector T cells and natural killer cells and activating the immune system, while reducing Tregs that suppress the immune system. No other molecule shows the same ability to increase the CD8:Treg ratio as imneskibart. What excites our team most is the clear link that we see between a higher CD8:Treg ratio and longer treatment duration as well as overall survival, which is making a real difference in patients’ lives.”

Study Design

Phase 1 of the trial is complete, and the phase 2 expansion is enrolling patients. The established RP2D is 9 mg/kg of imneskibart administered intravenously every 2 weeks, combined with a single dose (135K IU/kg) of aldesleukin on day 1 of each cycle. Efficacy is evaluated at the end of each 8-week cycle, with the possibility of patients receiving an additional dose of aldesleukin at the start of a new cycle based on tumor growth kinetics.

In the phase 2 expansion cohorts, patients with melanoma will receive imneskibart plus aldesleukin (RP2D), with the addition of nivolumab (480 mg every 4 weeks). Patients with NSCLC will receive imneskibart plus aldesleukin (RP2D), with the addition of avelumab (800 mg every 2 weeks). Comprehensive data are expected to be observed in mid-2026.

REFERENCES

1. New phase 2 data for Aulos Bioscience’s imneskibart reveal clinical activity in melanoma and non–small cell lung cancer. News release. BioSpace. November 10, 2025. Accessed November 12, 2025. https://tinyurl.com/3jsvh6fz

2. McKean M, Frentzas S, Powderly J, et al. Imneskibart (AU-007), a human monoclonal antibody (mAb) that binds IL-2 and prevents CD25 binding, + low-dose subcutaneous IL-2: phase 2 updated on CPI-refractory melanoma and non–small cell lung cancer (NSCLC). Presented at: Society for Immunotherapy of Cancer Annual Meeting; National Harbor, Maryland; November 2025. Poster 651.