PTX-100 is a potent small molecule that targets GGTase1, inhibiting a crucial post-translational modification required for the oncogenic activity of RAS family proteins. The clinical potential of PTX-100 was first highlighted in two Phase 1 dose-finding trials: one in solid tumors (TG-GTI-001) and one in hematologic malignancies (PTX-100 PD-012017). Given the significant role of the RAS/RHO family mutations in T-cell lymphoma, we initiated a Phase 1b study in patients with PTCL (n=11) and CTCL (n=8) across three dose levels.
PTX-100 demonstrated a safety profile, with no unexpected, treatment-related serious adverse events (SAEs) at doses up to 2000 mg/m²/day. Efficacy signals were promising, with an overall response rate of 45%, and 67% of evaluable patients experiencing sustained clinical benefit. These results underscore the potential of PTX-100 in T-cell lymphoma, a disease with limited therapeutic options.
To guide the Phase 2 trial design, comprehensive pharmacokinetic, pharmacodynamic, and dose-response modelling were conducted, alongside drug-drug interaction (DDI) studies. The Cmax of PTX-100 was dose-proportional, with no drug accumulation after 5 consecutive days of dosing. The drug was rapidly cleared between doses, with a half-life of approximately 9 hours. Importantly, drug exposure correlated strongly with clinical response. DDI studies also confirmed a favourable drug interaction profile, suggesting minimal risk of interference with other therapies.
Building on these compelling findings, a Phase 2, randomized study is now underway to evaluate the efficacy, safety, and pharmacokinetics of PTX-100 monotherapy in patients with relapsed or refractory CTCL. This study may provide a long-lasting therapeutic option for a disease with high unmet need.
