Imneskibart Regimens Show Activity in ICI-Refractory Melanoma, NSCLC

Regimens built on the investigational anti–IL-2 antibody imneskibart (AU-007) yielded responses and disease control in heavily pretreated patients with melanoma or lung adenocarcinoma that had progressed on immune checkpoint inhibitors (ICIs), according to findings presented at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting.

In a phase 1/2 trial (NCT05267626), imneskibart plus low-dose subcutaneous aldesleukin (Proleukin) and nivolumab (Opdivo) led to an objective response rate (ORR) of 28% (n = 5/18), counting 1 unconfirmed response, and a median progression-free survival (PFS) of 9.1 months (95% CI, 1.8-not estimable) in patients with melanoma refractory to dual ICI therapy. Without nivolumab, imneskibart plus aldesleukin produced a confirmed ORR of 29% (n = 4/14) and a median PFS of 6.9 months (95% CI, 1.7-22.3).¹

In patients with lung adenocarcinoma, imneskibart plus aldesleukin and avelumab (Bavencio) yielded a confirmed ORR of 21% (n = 3/14), a disease control rate (DCR) of 86%, and a median PFS of 5.8 months (95% CI, 1.8-11.7).²

"We believe these are exceptional results for imneskibart in [2] of the most challenging populations in oncology—[patients with] melanoma and NSCLC whose tumors have progressed despite multiple prior treatments," said Aron Knickerbocker, MBA, president and chief executive officer of Aulos Bioscience, in a news release.³

Mechanism and Study Design

Imneskibart, a human IgG1 monoclonal antibody, binds IL-2 and blocks its interaction with CD25. This prevents binding of IL-2 to the trimeric receptor on regulatory T cells (Tregs) while preserving signaling through the CD122/CD132 receptor on effector T cells and natural killer (NK) cells.^1,2

Earlier data from the study were presented at the 2025 SITC Annual Meeting.

Phase 1 dose escalation included 19 tumor type and was completed without dose-limiting toxicity. In the phase 2 dose expansion cohorts, all patients received imneskibart 9 mg/kg intravenously every 2 weeks with a subcutaneous aldesleukin loading dose of 135,000 IU/kg, given in 8-week cycles. A repeat aldesleukin dose was permitted at the start of a cycle if tumors were stable or growing on the prior scan. Nivolumab was given at 480 mg every 4 weeks and avelumab at 800 mg every 2 weeks in the respective melanoma and non–small cell lung cancer (NSCLC) cohorts.

Patients with melanoma had confirmed progression after at least 2 cycles of an anti–PD-1 agent combined with an anti–CTLA-4 or anti–LAG-3 agent. The NSCLC cohort enrolled patients with PD-L1–positive disease (tumor proportion score of 1% or higher) that had progressed on prior ICI therapy with or without chemotherapy. Responses were assessed by investigators per RECIST v1.1, and enrollment in the phase 2 cohorts is complete. The data cutoff reported at SITC was September 18, 2026.

Melanoma Efficacy Findings

The 20 patients in the nivolumab cohort had a mean of 2.7 prior lines of therapy. Among 18 response-evaluable patients, 1 had a confirmed complete response and 4 had partial responses, 3 of them confirmed. The DCR was 72%. Half of the patients had a PFS event, and the 6-month PFS rate was 61.1%. Overall survival (OS) data were immature after a median 5.6 months of follow-up; 16 of 20 patients were alive or censored.²

In the cohort of 31 patients treated without nivolumab, which included patients treated in the dose escalation portion, the mean number of prior lines of treatment was 2.4. Nine of 14 evaluable patients had stable disease, for a DCR of 93%. A patient with a complete response remained on study beyond 32 months. Median OS in this cohort was 16.1 months after 18 months of median follow-up (95% CI, 3.9-not estimable).

NSCLC Efficacy Findings

The cohort that received imneskibart plus aldesleukin and avelumab included 26 patients, 16 of whom had adenocarcinoma. Among those with adenocarcinoma, the mean number of prior lines was 2.6 (range, 1-6). The 3 responders had target lesion reductions of 42% to 45%, and 9 of 14 had stable disease. In the 17 patients included in the survival analysis, the 6-month PFS rate was 44.3%, median OS had not been reached (95% CI, 4.3-not estimable) at a median follow-up of 10.6 months, and the 12-month OS rate was 53.9% with 7 patient deaths at the time of follow-up. One patient with a response is continuing on the study for over 12 months.

Pharmacodynamics and Safety

Treatment lowered peripheral Treg counts and raised CD8/Treg ratios in both disease cohorts. In melanoma, patients whose Treg counts fell by more than the median of 56% had longer time to progression. In NSCLC, Treg counts stayed roughly 50% below baseline, and NK cell counts increased, which the investigators suggested could enhance antibody-dependent cellular cytotoxicity for avelumab.

Most drug-related adverse events (AEs) were grade 1 or 2, and no capillary leak syndrome or treatment-related deaths occurred. In 83 patients across tumor types who received imneskibart plus aldesleukin alone, grade 3/4 drug-related AEs occurred in 15%, most often transient lymphopenia; 1 patient had grade 4 cytokine release syndrome (CRS) that resolved without tocilizumab (Actemra).

With nivolumab in the melanoma cohort (n = 20), grade 3/4 drug-related AEs occurred in 20% and drug-related serious AEs in 25%; CRS (45%), fatigue (35%), and nausea (25%) were the most common drug-related AEs.

With avelumab in the NSCLC cohort (n = 26), grade 3/4 drug-related AEs occurred in 27% and drug-related serious AEs in 23%, including 2 cases of grade 3 adrenal insufficiency and 1 case of grade 4 cardiac failure that resolved within a month.

Clinical Context

The investigators compared the NSCLC results favorably with historical second-line docetaxel outcomes, especially considering that patients in this study were more heavily pretreated.³ Aulos also cited low historical median PFS outcomes with other ICI-containing regimens in PD-1–refractory melanoma, including the phase 2 LEAP-004 trial (NCT03776136) of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) and the RELATIVITY-020 trial (NCT01968109) of nivolumab plus relatlimab (Opdualag).

The investigators stated that the findings support randomized trials in ICI-refractory lung adenocarcinoma vs standard therapy, as well as further evaluation in patients with melanoma refractory to dual ICI.

"With deep and durable tumor responses, consistent pharmacodynamic activity and manageable safety profiles, these findings provide a compelling foundation for advancing into randomized clinical trials and reinforce our confidence in imneskibart's differentiated mechanism and its potential to become an important new treatment option in both melanoma and lung cancer," Knickerbocker stated in the news release.³

REFERENCES

1. Aulos Bioscience's Imneskibart Demonstrates Outstanding Phase 2 Activity in Checkpoint Inhibitor-Refractory Melanoma and Lung Cancer, Comparing Favorably With Historical Treatment Benchmarks. News release. Aulos Bioscience. November 6, 2026. Accessed November 9, 2026. https://tinyurl.com/mvb9nyhc

2. McKean M, Haydon A, Frentzas S, et al. Imneskibart + low-dose subcutaneous IL-2 ± nivolumab in doublet checkpoint inhibitor-refractory melanoma: promising activity in an ongoing phase 1/2 study. Presented at: Society for Immunotherapy of Cancer 41st Annual Meeting; November 4-8, 2026; Phoenix, AZ. Poster 611.

3. Govindan R, Blumenschein GR, Oakman C, et al. Imneskibart, a human monoclonal antibody (mAb), + low-dose subcutaneous IL-2 + avelumab: phase 2 promising activity in ICI-refractory adenocarcinoma non-small cell lung cancer (NSCLC). Presented at: Society for Immunotherapy of Cancer 41st Annual Meeting; November 4-8, 2026; Phoenix, AZ. Poster 605.

4. 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, MD; November 5-9, 2025. Poster 651.