Modulating MDSCs by HF1K16: A mono-therapy phase Ia study examining safety and preliminary efficacy in patients with refractory and metastatic cancer.

Abstract

e14040 Background: Immature myeloid cells or the so called Myeloid-derived suppressor cells (MDSCs) are found to be present in higher numbers in cancer patients' PBMCs and in tumor infiltrating cells. All-trans retinoic acid (ATRA) is a natural vitamin A metabolite that's capable of inducing MDSC maturation and differentiation at uM concentrations. HF1K16 is an ATRA liposome formulation developed by Hangzhou Highfield Biopharm that aims to deliver ATRA to the tumor microenvironment by i.v. infusion for MDSC mediated immuno-therapeutic effects. Methods: The HF1K16 phase Ia clinical trial (NCT05388487) is being conducted to study the tolerability and safety of HF1K16 in patients with refractory solid tumors based on a "3+3" dose escalation scheme. HF1K16 infusions were given every other day for 2 weeks followed by a break week, and the 3wk cycle were repeated until EOT. Safety and tolerability records, repeated dose PK parameters, as well as exploratory PD analysis of PBMC samples are evaluated during the first cycle of treatment. Efficacy evaluations are followed every 6 weeks or less until EOT. Results: As of January 30, 2023, there have been 11 patients enrolled into the study in the dose groups of 45 mg/m2, 90mg/m2 and 120 mg/m2. The patient diagnosis and up to date treatment information is shown. Clinical trial information: NCT05388487 . Conclusions: HF1K16 is well tolerated at the 45 mg/m2 and 90 mg/m2 dose levels when given as monotherapy. Using the RECIST 1.1 criteria, one patient achieved an objective response with a progressive reduction of the target lesion from 70mm to 23.7mm. Four patients had PFS longer than 3 months. There is a subgroup of five enrolled patients who have recurrent and refractory Glioblastoma with multiple prior treatments. Three of them had control of disease and are still under treatment. The study is also still on going. We will collect more data based on additional enrolled cases and plan for the next phase study of HF1K16. [Table: see text]