Dosing of PAS-004 Begins in Patients in MAPK-Driven Tumors

Enrollment and initial dosing of PAS-004 at 30 milligrams has begun in three patients with MAPK pathway driven advanced solid tumors, according to a news release from Pasithea Therapeutics.

“We are pleased to have recruited, enrolled and commenced dosing of the initial three subjects in Cohort 6 more rapidly than anticipated and we currently expect to complete enrollment of all patients in the trial by the end of 2025,” Dr. Tiago Reis Marques, chief executive officer of Pasithea, said in the release.

The ongoing phase 1 clinical trial is a multicenter, open-label, dose-escalation study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of PAS-004 in patients with advanced solid tumors driven by the MAPK pathway. Notably, this includes patients with documented RAS, NF1 or RAF mutations, or those whose disease progressed after BRAF/MEK inhibition.

Investigation participants will have regular visits with the study doctor and will undergo tests and exams to monitor their health and safety. All of those eligible for the trial will take PAS-004 by mouth as a single dose followed by a one-week observation period, then once daily during the study in 28-day cycles. They will continue taking PAS-004 daily for up to two years or until they choose to withdraw from the study, experience unacceptable side effects, have disease progression or another illness that interferes with treatment or if the sponsor stops the study.

This study has seven locations in the United States: Austin, Texas 78758; Irving, Texas 75039; San Antonio, Texas 78229; and Fairfax, Virginia 22031. This study also includes locations in Bulgaria and Romania: Sofia, Bulgaria 1404; Bucharest, Romania 022328; and Cluj-Napoca, Romania RO-400015.

Preliminary Findings of PAS-004

The investigational MEK inhibitor PAS-004 was found to be safe and tolerable in early testing among patients with advanced cancers linked to the MAPK pathway.

This is according to preliminary findings from two cohorts of patients that were enrolled in the phase 1 trial.

In the first two dosing groups, six patients were treated with either 2 milligrams or 4 milligrams of PAS-004. The treatment showed a manageable safety profile, with no drug-related interruptions, dose reductions, or discontinuations reported. Researchers observed no serious side effects tied to the drug and no criteria for halting the study were met. So far, no skin, gastrointestinal, or eye-related side effects have been seen at either dose level.

“We believe these data demonstrate a pharmacokinetic and safety profile that differentiates PAS-004 as a next-generation MEK inhibitor,” Dr Tiago Reis Marques, chief executive officer of Pasithea Therapeutics, stated in a news release. “The long half-life at approximately 70 hours and the ability to achieve a flat pharmacokinetic curve at steady-state, aim to provide a constant target inhibition while avoiding peak plasma toxicities, which is a unique pharmacokinetic profile among MEK inhibitors used for the treatment of NF1[-mutated cancers].”

The study evaluated PAS-004 in a sequential dose-escalation design with doses of 2 milligrams, 4 milligrams, 8 milligrams, 15 milligrams, 22 milligrams, 30 milligrams, 37 milligrams and 45 milligrams.

Primary end points included dose-limiting toxicities, side effects, hematology and clinical chemistry parameters.

“PAS-004 has demonstrated distinct properties that we believe are significant advantages for an oral MEK inhibitor. PAS-004 has a significantly longer half-life compared to early-generation MEK inhibitors, particularly those used for the treatment of NF1[-mutated cancers], which have half-lives of less than eight hours,” Marques added.

For more information regarding the trial, please visit www.clinicaltrials.gov using the identifier: NCT06299839.

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