A phase Ia study of the myeloid-derived suppressor cell modulator HF1K16 in refractory and metastatic cancer patients: Preliminary efficacy and safety

BackgroundMyeloid-derived suppressor cells (MDSCs) represent a significant immunosuppressive mechanism and are found in higher numbers in cancer patients’ peripheral blood mononuclear cells (PBMCs) and in the tumor microenvironment. All-trans retinoic acid (ATRA) is a natural vitamin A metabolite. There is a substantial body of evidence indicating that ATRA can induce MDSC maturation and differentiation. HF1K16 is a drug encapsulated immune modulating liposome containing all-trans retinoic acid.MethodsThis phase Ia trial (NCT05388487) was conducted to study the tolerability and safety of HF1K16 in patients with refractory solid tumors based on a “3+3� dose escalation scheme (45, 90, 120, 160 mg/m2). Eligible patients had prior confirmed advanced solid tumor and failed SOC. HF1K16 infusions were administered in 21-day cycles (q.o.d days 1-14) and repeated until EOT. Safety and tolerability records, repeated dose PK parameters, and exploratory PD analysis of PBMC samples are evaluated during the first treatment cycle.ResultsA total of 17 cancer patients were enrolled in the study into dose groups of 45 mg/m2 (n=4), 90 mg/m2 (n=5), 120 mg/m2 (n=4) and 160 mg/m2 (n=4). HF1K16 was well tolerated and the most common AE was dizziness, nausea, vomiting, excessive sweating, and flushing (≤2 grade). Using the RECIST 1.1 criteria, the overall disease control rate (DCR) was 35.71%, the mOS was 8.5m and the mPFS was 1.4m. There were 5 patients had been previously treated with I.O. Their PBMC immunological profiling during first cycle was collected at day 1, 7, 14, and 21 for a longitudinal study. 4/5 achieved reduction of MDSC (see the table). Table: 1002P Enrollment of I.O failure patients No. of patient #1 #2 #3 #4 #5 Primary site Colorectal Stomach Colorectal Lung Liver Prior treatment S: Surgery C: Chemotherapy R: Radiotherapy I.O: Immuno Oncology T: Targeted therapy S+C+I.O. S+C+T+I.O. S+C+T+I.O. C+T+I.O. S+R+C+I.O. Longitudinal study of MDSC population (% of Monocyte) D1 31.0 15.2 28.8 11.0 40.1 D7 12.5 32.3 10.8 13.9 29.8 D14 8.7 22.4 14.4 5.3 12.6 D21 18.5 28.5 13.5 10.3 39.5 Longitudinal study of NK Cells (% of PBMC) D1 10.3 37.4 23.2 2.8 5.0 D7 14.1 44.3 16.8 3.6 14.8 D14 8.8 40.7 22.9 2.6 10.9 D21 11.4 51.4 14.6 4.1 9.9 ConclusionsWhile the interpretation of our data is limited by the small sample size, the results provide an encouraging signal and warrants further assessment. We are currently conducting an advanced glioma-specific expansion arm and patient recruitment continues with anticipated completion in 2024.Clinical trial identificationNCT05388487.Legal entity responsible for the studyThe authors.FundingHighField BioPharmaceuticals Corporation.DisclosureA. Zheng: Financial Interests, Personal, Full or part-time Employment: HighField BioPharmaceuticals Corporation. Y. Xu: Financial Interests, Personal and Institutional, Stocks or ownership: HighField BioPharmaceuticals Corporation. All other authors have declared no conflicts of interest.