CTNI-10. A PHASE 1/2 TRIAL OF FOG-001, A FIRST-IN-CLASS DIRECT β-CATENIN:TCF4 INHIBITOR: SAFETY AND PRELIMINARY ANTITUMOR ACTIVITY IN ADAMANTINOMATOUS CRANIOPHARYNGIOMA (ACP) PATIENTS

Abstract BACKGROUND ACPs are brain tumors that typically originate in the suprasellar region and are associated with significant morbidity, with patients experiencing visual impairment, pituitary dysfunction and headaches. No systemic therapies are available for ACP, while surgery or radiation can be challenging and result in complications. Almost all ACPs have Wnt pathway-activating mutations (WPAMs), predominantly CTNNB1 activating mutations. FOG-001 is a Helicon™ peptide that competitively inhibits the interaction between β-catenin and TCF transcription factors in the Wnt-signaling pathway. Here we report safety and preliminary efficacy of FOG-001 in ACP patients. METHODS This is a first-in-human, phase 1/2, multicenter study of FOG-001 in patients with WPAM+ solid tumors, treated at doses ranging from 36-480 mg/m2 (NCT05919264). Patients with histologically confirmed, locally-advanced ACP are eligible. Disease assessments, per RECIST v1.1, are performed every 8 weeks for 48 weeks and every 12 weeks thereafter. Primary objective is safety and tolerability of FOG-001. Secondary objective is anti-tumor activity. RESULTS As of May 11, 2025, 3 ACP patients have received FOG-001 monotherapy at doses of 144 mg/m2 (n=1) and 360 mg/m2 (n=2). All patients are male and median age is 42 years (range 19-62). All patients had prior surgery and 1 received radiation. All treatment-related adverse events (TRAEs) were low-grade (no Grade ≥3 TRAEs). The most common TRAEs were hyponatremia (n=2) and thrombocytopenia (n=2), both reversable. No treatment-related serious adverse events or dose reductions have been reported. Tumor size has decreased in all patients, with one patient achieving a partial response (PR), with a 48.0% reduction, and the other two stable disease (24.0% and 19.2% decrease). CONCLUSIONS FOG-001 has been well tolerated in patients with locally-advanced ACP. All patients have had tumor size reductions, including one PR, suggesting that the Wnt-signaling pathway is an actionable target in ACP.