Abstract CT039: Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101)

Abstract Background: Systemic delivery of IL-12 is limited by significant toxicity. To achieve therapeutic doses without toxicity, IL-12 was conjugated to aluminum hydroxide (ANK-101) and a Phase I clinical trial was conducted to determine safety, PK, and biologic activity in patients with advanced solid accessible tumors. Methods: A modified dose-escalation Phase 1 study was conducted (NCT06171750) in patients with accessible, advanced solid tumors progressing following standard therapy. ANK-101 was administered at escalating doses with volume adjusted based on tumor diameter. Adverse events were reported per NCI CTCAE, version 5. Serum was collected at specified cycles for pharmacokinetic (PK), interferon-γ (IFN-γ), serum cytokines, and anti-drug antibody (ADA) titers. Whole blood was obtained for peripheral immune cell analysis by flow cytometry. Serial tumor biopsies were obtained for PD-L1 expression, immune cell characterization by IHC and gene expression was evaluated by Nanostring. Tumor measurements were performed every 12 weeks. Statistical analysis was primarily descriptive with categorical variables summarized with numbers and percentages while continuous variables were calculated as mean, standard deviation, median, and range. P≤ 0.05 was considered significant. Results: 15 pts were enrolled (median age: 68 years). 60% were female and 60% had baseline ECOG score of 0. Notably, 73.3% of those enrolled had received > 3 lines of prior therapy. Seven patients had melanoma, 4 had squamous cell cancer of the head and neck, 2 had breast cancer, and 1 each had bladder and apocrine adenocarcinoma. No patients experienced drug-limiting toxicity while on study and no patients discontinued study treatment due to an adverse event. There were no ≥ Grade 3 treatment-related adverse events. There were two Grade 1 CRS-related fevers. PK analysis showed a trend towards dose response but demonstrated overall low systemic exposures of ANK-101. ADA were detected in one patient treated after three cycles. Biologic activity was further confirmed by an increase in serum IFN-γ with peak levels ranging 18-496 pg/mL 24 hrs after treatment. ANK-101 induced local expression of PD-L1 and recruitment of CD8+ T cells and increased local gene expression consistent with immune activation. To date, 11 subjects are evaluable for response with a disease control rate of 63.6% and best objective responses include 1 PR, 7 SD, and 3 PD. 6 subjects remain on active treatment. Conclusions: ANK-101 is well tolerated at doses tested, demonstrated biologic activity, and was associated with durable disease control across different tumors in a heavily pretreated population. Further investigation is warranted. Citation Format: Jong Chul Park, Brendan Curti, Marcus O. Butler, Gail Iodice, Sailaja Battula, Joseph Elassal, James L. Gulley, Jeffery Schlom, Howard L. Kaufman, John M. Kirkwood. Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT039.