Announcement • Jun 30
Pasithea Therapeutics Reports Positive Interim Phase 1 Advanced Cancer Study Data And Protocol Expansion Pasithea Therapeutics Corp. announced updated interim safety and clinical activity data from its ongoing first-in-human trial evaluating PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation, including patients who have failed prior BRAF/MEK inhibitor treatment. PAS-004 has been well-tolerated, with all treatment-related adverse events (TRAEs) being Grade 1 or 2, no observed cardiac or retinal treatment-related events, and low rates of rash and gastrointestinal toxicities. Protocol amendment extends dose escalation to higher levels: continued dose escalation using tablet formulation to explore 18mg, 24mg, 30mg, 40mg, and up to 52mg dose levels to further characterize safety, pharmacokinetics (PK), and early efficacy signals at higher doses. Interim PK and safety data at pharmacologically active doses support PAS-004 as a differentiated candidate with potential for long-term chronic dosing with favorable tolerability. An optional pilot food effect assessment has been introduced to evaluate the impact of fed vs. fasted administration on PAS-004 pharmacokinetics, to optimize long-term dosing strategy. 34 patients have been enrolled and dosed. Heavily pre-treated population with a median of 3 prior lines of therapy (range 1 – 8). Difficult to treat diagnoses (e.g., refractory pancreatic cancer and ovarian cancer), including 12 patients with BRAF V600E mutations, 10 of whom previously progressed on BRAFi and/or BRAFi/MEKi combinations. Well-tolerated safety profile with long-term, once daily dosing. No dose-limiting toxicities (DLTs), and no discontinuations due to TRAEs with 10 patients on study for >90 days, of which 6 patients >150 days, 4 patients >300 days, and 2 patients >365 days. All TRAEs were Grade 1 or Grade 2; low cumulative rates of rash (12%) and diarrhea (6%) across all patients at all doses throughout the study, including no (0%) rash or diarrhea in the 4 patients on study >300 days and 2 patients >365 days. No events of retinal or cardiac toxicity. Disease stabilization in the refractory population (N=12). Multiple patients demonstrating durable clinical benefit and tumor shrinkage, including several MEK/BRAF-pretreated patients who have remained on study for greater than six months and two patients on study for over one year – exceeding the approximately 5-month median progression-free survival reported in the literature for BRAF/MEK rechallenge in this setting. The final progression-free survival data will not be known until the end of the trial. Pharmacokinetics support daily dosing and exploration of higher dose levels. Long half-life (approximately 60 hours). Linear, dose proportional PK. Cmax/Cmin ratio. Announcement • Jun 16
Pasithea Therapeutics Amends Clinical Study Protocol for Phase 1/1B Nf1 Clinical Trial Pasithea Therapeutics Corp. has amended the clinical study protocol for the Phase 1/1b trial of PAS-004 in neurofibromatosis type 1 (NF1) patients with symptomatic inoperable, incompletely resected, or recurrent plexiform neurofibroma (PN). The amendments include an update to the dose escalation part of the study (Part A) to allow for the enrollment of additional participants at two additional higher dose levels (24mg and 32mg), the ability to backfill completed dose cohorts (4mg, 8mg, 12mg and 18mg) with up to two participants, and the evaluation of intermediate dose levels. In addition, the protocol amendments allow patients to remain on treatment for up to 18 months in Part A, and include additional MRI scans to comprehensively evaluate PN, as well as adding more detailed cutaneous neurofibroma (CN) measurements, including tumor height and volume. Pasithea has completed enrollment and multi-cycle dosing of the initial 4mg, 8mg, 12mg and 18mg cohorts, and enrolled the 24mg cohort and an intermediate 15mg cohort. This multicenter, phase 1/1b, open-label study is dividend into two parts: a dose-escalation phase (part A) and an expansion cohort phase (part B). To date, the dose-escalation phase has enrolled and dosed 18 patients with NF1. 
