A phase 1 study of PHST001, an anti-CD24 monoclonal antibody, in adult patients with advanced relapsed and/or refractory solid tumors.

Abstract

TPS2685 Background: Macrophages are the most abundant immune cells in tumors and can directly phagocytose tumor cells and promote broad anti-tumor immunity. However, phagocytosis can be inhibited by macrophage checkpoints, also known as ‘don’t eat me’ signals. One such checkpoint is the immunomodulatory protein CD24 that is overexpressed in many tumors and associated with poor clinical prognosis. CD24 inhibits macrophage phagocytosis of tumor cells via binding to Siglec-10 on macrophages. PHST001 is a high affinity anti-CD24 IgG4 antibody that blocks multiple glycoforms of CD24 and induces macrophage phagocytosis of tumor cells in a wide range of preclinical models. In addition, PHST001 improves tumor control and survival in murine models when combined with multiple chemotherapies as chemotherapy-induced tumor cell stress may improve macrophage phagocytosis of tumor cells when combined with CD24 blockade. Thus, CD24 blockade has potential as monotherapy and in combination with other cancer therapies to enhance tumor cell phagocytosis and improve patient survival. Methods: PHST001-101 is an open-label, first-in-human, Phase 1 study in patients ≥ 18 years of age with advanced relapsed and/or refractory solid tumors (NCT06840886). In Phase 1a, patients receive escalating doses of PHST001 administered Q3W as an IV infusion at one of nine dose levels. Phase 1b combines PHST001 with chemotherapy in patients with ovarian cancer, endometrial cancer, or cholangiocarcinoma in safety run-in groups and tumor-specific expansion cohorts. Key inclusion criteria include age ≥ 18 years, evidence of measurable disease, an ECOG performance status of 0 or 1, and adequate organ function. Key exclusion criteria include a diagnosis of immunodeficiency, active CNS disease, or active autoimmune disease. The primary objective is to assess the safety and tolerability of PHST001 as monotherapy and in combination with chemotherapy, and to assess the preliminary antitumor activity of PHST001 in combination with chemotherapy. Secondary objectives include assessing antitumor activity of monotherapy and pharmacokinetics (PK) of PHST001. Exploratory objectives include evaluating the relationship between PK and pharmacodynamics (receptor occupancy, cytokine profiling, changes in ctDNA, and immune cell subsets in the tumor), immunogenicity of PHST001, antitumor activity in patients treated beyond progression, and patient-reported outcomes. The study enrolled the first patient treated in April 2025 and is currently enrolling patients in Phase 1a at Dose Level 8 (18 mg/kg) with no DLTs to date. Enrollment in Phase 1b is anticipated to begin in early 2026. Clinical trial information: NCT06840886 .