Pasithea Therapeutics presents updated interim data from Phase 1 PAS-004 study

Pasithea Therapeutics (KTTA) announced updated interim results from its ongoing dose escalation Phase 1 study evaluating PAS-004 in advanced cancer patients in a poster presentation at the American Society of Clinical Oncology 2025 Annual Meeting The Phase 1 clinical trial is a multi-center, open-label, dose escalation, modified 3+3 study design to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy of PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, or patients who have failed BRAF/MEK inhibition. As of the cut-off date of April 2, 2025, a total of 21 patients had been enrolled and received at least one dose of PAS-004 in six cohorts. The most common cancer diagnosis was pancreatic cancer, colorectal cancer, and melanoma. All treatment-related adverse events have been either grade 1 or grade 2. No known MEK inhibitor class-related AEs such as ocular toxicities, cardiotoxicities, and skin toxicities were observed during the DLT observation period. No DLTs were reported, and dose escalation is ongoing. Preliminary PAS-004 PK analysis suggests linear PK with an estimated half-life in excess of 60 hours. The Cmax to Cmin ratio was below 2 at steady state in all dose levels and has achieved potentially sufficient exposures for target engagement. This is supported by previously reported preliminary pERK inhibition observed in cohort 3, with pERK inhibition of up to 91%. PAS-004 has demonstrated a dose-dependent PK profile and preliminary clinical activity as a monotherapy in patients with heavily pre-treated, refractory solid tumors. In the efficacy evaluable population, early response evaluation reveals stable disease by RECIST 1.1 in 10 patients at some point during the trial, with progression free survival of up to 159 days and overall survival of up to 253 days. In Cohort 4A, two out of three patients achieved stable disease and remain on therapy. One patient with stage 4 KRAS G12R-mutated pancreatic cancer, having progressive disease while on three prior lines of therapy, achieved a tumor diameter reduction of -9.8% and remains on study for over 5 months. The second patient with Stage 4 BRAF-mutated melanoma, having progressed on two prior lines of therapy, including a prior MEK inhibitor + BRAF inhibitor combination treatment, achieved tumor diameter reduction of -14.9% and remains on study for over 5 months.