Abstract CT130: Initial results from a phase 1 study of PHST001, a macrophage activating anti-CD24 antibody, in patients with advanced/metastatic solid tumors

Abstract Background: Macrophages are the most abundant immune cell in tumors and can phagocytose tumor cells and promote broad anti-tumor immunity. However, phagocytosis can be blocked by macrophage checkpoints, also known as ‘don’t eat me’ signals. One such signal is CD24 which inhibits macrophage phagocytosis of tumor cells via binding to Siglec-10. CD24 expression is elevated in many tumors and associated with poor clinical prognosis. PHST001 is a high affinity anti-CD24 IgG4 antibody that blocks CD24, potently inducing macrophage phagocytosis of tumor cells in a wide range of in vitro and in vivo preclinical models. Methods: PHST001-101 is a first-in-human, dose escalation study of PHST001 in adult patients with relapsed/refractory, advanced/metastatic solid tumors (NCT06840886). This Phase 1 study is composed of a Phase 1a monotherapy dose escalation and a Phase 1b combining PHST001 with chemotherapy. In Phase 1a, patients received PHST001 at 1 of 9 dose levels and in backfill cohorts at select dose levels via IV infusion every 3 weeks. The primary objective of this study is to assess the safety and tolerability of PHST001. Results: As of 27 Jan 2026, 43 patients have been treated in Phase 1a at 7 dose levels (0. 1 mg/kg to 9 mg/kg). No patients have experienced a dose limiting toxicity and no patients have discontinued PHST001 or died due to a treatment-related adverse event (TRAE). Most TRAEs are transient and Grade 1/2. The most common TRAEs (10%) include fatigue (21%), neutrophil count decreased (19%), nausea (14%), and chills (12%). Grade 3/4 TRAEs occurring in more than one patient include neutropenia (12%) and hypotension (5%). Neutropenia has been asymptomatic with no concurrent infections and resolves in ≤ 7 days. PK analysis shows a favorable and linear PK profile of PHST001 with dose proportional increase in exposure and no target mediated drug disposition. Peripheral receptor occupancy (RO) of up to 95% is achieved starting at 2 mg/kg and PK/RO modeling suggests ≥ 50% RO in the tumor at 4 mg/kg. In 28 patients with at least one RECIST assessment, best objective responses include 13 patients (46%) with stable disease and 15 patients (54%) with progressive disease (PD). 5 patients had a decrease in tumor size including 1 patient with a decrease after being treated beyond PD; all at doses ≥ 4 mg/kg. Pharmacodynamic changes include decreases in serum tumor markers and ctDNA, as well as elevations in cytokines and chemokines associated with macrophage/myeloid cell activation. Additional data, including from higher dose levels, will be presented. Conclusions: PHST001 is well tolerated at doses evaluated to date with TRAEs being predominantly low grade and reversible. The PK profile of PHST001 confirms favorable exposure with sustained target engagement. Signals of clinical activity are emerging at higher dose levels. Combination with other therapies, such as chemotherapy, are currently being explored in Phase 1b. Citation Format: Stephane Champiat, Ulka Vaishampayan, Michael Cecchini, Oliver Dorigo, Anthony El-Khoueiry, Gina Fleming, Niharika Mettu, Michael J. Dennis, Elizabeth Davis, Susan Luebbe, Jen Cao, Roy Maute, Raphael Rousseau, Kyriakos Papadopoulos. Initial results from a phase 1 study of PHST001, a macrophage activating anti-CD24 antibody, in patients with advanced/metastatic solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT130.