Exploratory phase I study of HF1K16 for the treatment of patients with refractory/recurrent advanced glioma: Preliminary efficacy and mechanism as a monotherapy.

person Ruofan Huang Huashan Hospital, Fudan University, Shanghai, China info_outline Ruofan Huang, Anjie Zheng, Yuhong Xu, Xiaochen Zhang, Jinsong Wu

Authors person Ruofan Huang Huashan Hospital, Fudan University, Shanghai, China info_outline Ruofan Huang, Anjie Zheng, Yuhong Xu, Xiaochen Zhang, Jinsong Wu Organizations Huashan Hospital, Fudan University, Shanghai, China, Zhejiang University, School of Pharmacy, Hangzhou, China, Hangzhou HighField Biopharmaceuticals Corporation, Hangzhou, China, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Abstract Disclosures Research Funding Hangzhou Highfield Background: The absence of I.O success in advanced glioma treatment suggests that a deeper understanding of the brain tumor and the immune microenvironment is critical. It is well-documented that refractory/recurrent glioma has an immunosuppressive nature. One frequent observation is the high level of circulating myeloid-derived suppressor cells (MDSCs). We conducted a exploratory study to assess an immunomodulatory approach for relieving immune suppression employing HF1K16, a liposome all-trans retinoic acid (ATRA) suspension. Methods: This Phase I study (NCT05388487) comprise a conventional 3+3 dose escalation plus an advanced glioma-specific expansion arm. Eligible patients had prior confirmed advanced solid tumor and failed standard treatment. HF1K16 infusions were administered in 21-day cycles (q.o.d days 1-14). Prior to and during treatment, peripheral blood mononuclear cells were collected and analyzed with flow cytometry to monitor the changes in myeloid cell phenotype and T cell composition. Survival data were calculated as it is difficult to determine the timing of progression for immunotherapies owing to pseudoprogression. Results: As of Feb 2th, 2024, 14 recurrent/refractory glioma patients including 6 males and 8 females had been enrolled in this study. 2 of them withdrew before finished 1st cycle. 7 had received treatment for at least 3 cycles and 1 had achieved CR after 15 cycles. For the 8 primary diagnosed grade IV glioma patients, the mOS is 7.8m, and 6 (75%) are alive. The mOS for the primary dignosed grade II/III is 13.7m and 100% patients are alive (n=4). There is 1 recurrent GBM patent who had received 5 cycles of treatment. MRI showed an enlargement of tumor lesion while KPS score remained >90. A surgical resection was performed and we subsequently studied the posttreatment tumor specimens (window of opportunity). IHC and flow cytometry analysis revealed prominent perivascular and intratumoral inflammatory infiltrate, containing CD8+CTL cells and HLA-DR expressing cells. Conclusions: While the interpretation of our data is limited by the small sample size, the results provide an encouraging signal and warrants further assessment. Patient recruitment continues with anticipated completion in 2024. Clinical trial information: NCT05388487. Primary diagnosis glioma grade and prior treatment history. Grade IV Grade II & III (n=9) (n=5) Surgery 9 5 Temozolomide 9 5 Anlotinib 2 0 Bevacizumab 2 0 Tumor Treating Fields 2 0 Radiation Therapy 9 5 Sintilimab 1 0 DC vaccine 1 0 The most common treatment-related adverse events (AEs) Event Treatment-related Adverse Events All Grades Grade Grade 3 4 Skin peeling 10 0 0 Headache 8 0 0 Hypercholesterolemia 9 2 0 Elevated low-density lipoprotein 1 1 0 Hypertriglyceridemia 6 1 0 Thrombophlebitis 1 1 0

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