Abstract LB205: Myeloid cell targeted immune modulation in solid tumor and brain tumor patients: An analysis of nct05388487 phase 1 study data

Abstract Background: T-cell-based immunotherapy has proven effective in many solid tumors, but its wider application remains challenging, especially for gliomas. MDSCs in the peripheral blood mononuclear cells (PBMCs) and tumor microenvironment were considered to be a major factor affecting the response rate of ICB. All-trans retinoic acid (ATRA) is a natural vitamin A metabolite, and evidence suggests that ATRA can induce MDSC maturation and differentiation for the benefit of cancer treatment. The NCT05388487 trial was designed to test the safety and preliminary efficacy of ATRA liposomes (HF1K16) in last-stage solid tumor patients. This study aimed to analyze the dynamic change of immune cells and tumor microenvironment during the treatment. Methods: HF1K16 was administered in 21-day cycles (every other day on days 1-14) until the end of treatment (EOT). PBMC samples were collected during the treatment. Flow cytometry was used to evaluate changes in myeloid cell phenotypes and T-cell composition. In certain cases, surgically removed tumor tissue from patients who had been treated multiple cycles were obtained and analyzed. Results: All the patients with non-glioma solid tumors had received extensive prior treatment including surgery, target therapy, chemotherapy, and cancer metastasis. 6 out of the 10 patients had prior ICB. The levels of MDSCs were in general much higher than those in healthy donors. When analyzed at C1D1, C1D7, C1D13, and C1D21 during the 1st cycle of treatment, a decline of MDSC level was observed in 9 out of the 10 patients. Concurrently, an increase of NK cells was observed in 7 out of 10 patients. In particular, the HF1K16 single-agent treatment had significant efficacy in refractory and recurrent glioma patients. Notably, one patient had a complete response (CR) after 10 cycles of dosing. This patient received continuous treatment for 24 months and has been cancer-free for exceeding 20 months. Out of the 8 patients who were first diagnosed with grade 2∼3 glioma, the median progression-free survival (PFS) is 90d. The mOS has not been reached but is estimated to be longer than 272d. Especially for patients with T naïve cells≥20% in CD3 T cells before treatment, the PFSTn≥20% is 202.5d (n=4), with HR=0.13. Cl95%= 0.018 to 0.858. For the treatment of rrGBM patients, The mOS is 317d. The median PFS for them is 64d. Most importantly, we collected the surgical removed tumor tissue from one patient who achieved SD for 5 cycles of treatment but progressed. For the treatment of rrGBM patients, The median mOS is 317d. The median PFS for them is 64d. Most importantly, we collected the surgical removed tumor tissue from one patient who achieved SD for 5 cycles of treatment but progressed. A notable finding was the increased presence of CD8+CTL cells and HLA-DR-expressing cells as compared to tissue samples obtained during the initial surgical. Notably, this patient has maintained a tumor-free status post-surgery, with no intervention required, for a period exceeding 11 months. Conclusions: HF1K16 treatments were shown to be safe and well tolerated with limited side effects. Significantly reducing the proportion of MDSC was achieved. This myeloid-targeting immunotherapy approach may offer a novel therapeutic strategy for the treatment of brain tumors. Furthermore, HF1K16 could be used in combination with other drugs for non-glioma tumors. Citation Format: Anjie Zheng, Ruofan Huang, Yuhong Xu, Jinsong Wu. Myeloid cell targeted immune modulation in solid tumor and brain tumor patients: An analysis of nct05388487 phase 1 study data [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 LB205.