FOG-001 Shows Early Activity in Patients With Desmoid Tumors

Clinical Summary: 

• Design/Population: This phase 1/2 study evaluated FOG-001 in patients with desmoid tumors harboring Wnt pathway-activating mutations, including those previously treated with systemic therapy.
• Key Outcomes: FOG-001 demonstrated early antitumor activity, with partial responses observed in 50% of evaluable patients and disease control achieved in all patients. Treatment was generally well tolerated with manageable adverse events.
• Clinical Relevance: Direct inhibition of β-catenin may offer a novel therapeutic strategy in desmoid tumors. These findings support further clinical development of FOG-001 in this population.

Results from a phase 1/2 study demonstrate that FOG-001, a β-catenin inhibitor, shows early clinical activity with manageable safety among patients with desmoid tumors.

“Wnt pathway-activating mutations (WPAMs) are highly prevalent in desmoid tumors, almost all of which harbor a WPAM in APC or CTNNB1,” stated Gregory Cote, MD, PhD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, and coauthors. “Given the causal nature of WPAM mutations in desmoid tumors, targeting β-catenin offers a more direct and disease-relevant approach than γ-secretase inhibitors, which inhibit Notch signaling.”

In this study, 4 patients with Wnt pathway-activated desmoid tumors who had received at least 1 prior line of systemic therapy or were treatment-naive but considered appropriate for participation received FOG-001 at doses ranging from 72 mg/m² to 480 mg/m². The primary end points were safety and tolerability. A key secondary end point was antitumor activity. 

At analysis, 2 patients achieved a partial response, including 1 patient who had progressed on prior nirogacestat. Remaining patients had stable disease with tumor reductions of 10.8% and 20.4%, resulting in a disease control rate of 100%. Treatment durations ranged from 33 to 77 weeks. The most common treatment-related adverse events included alopecia (n = 4), AST increase (n = 3), epistaxis (n = 3), fatigue (n = 3), nausea (n = 3), and hyperbilirubinemia (n = 3). 

“Preliminary data show that FOG-001 has acceptable tolerability in pts with desmoid tumors. Tumor reductions were seen in all pts, including a PR in a pt who progressed on prior nirogacestat,” concluded Dr Cote et al. “Dose expansion in a desmoid-specific cohort is currently ongoing.” 

Source: 

Cote GM, Cecchini M, Papadopoulos KP, et al. A phase I/II trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor - Safety and preliminary antitumor activity in patients with desmoid tumors. Ann Oncol. Published online: September 2025. doi:10.1016/j.annonc.2025.08.3299