Clinical stage oncology company Prescient Therapeutics (ASX: PTX) has confirmed a phase 1b basket study of its cancer drug PTX-100 will proceed to the next dose level following successful completion on the first cohort of patients and achievement of acceptable safety parameters.
The open label, non-randomised study at Melbourne’s Epworth Hospital seeks to evaluate the pharmacokinetics and pharmacodynamics of PTX-100, as well as the safety and efficacy of up to three different doses in patients with advanced malignancies where Ras and RhoA protein mutations are prevalent.
The study takes a “basket” approach to assess the drug on multiple cancers with a view to addressing specific mutations, rather than tumour origin.
Basket studies pioneered by several US companies have quickly identified patient populations who could benefit from the investigational drug, sometimes leading to fast-track approval.
An earlier US study in patients with advanced solid tumours showed PTX-100 was well tolerated and achieved stable disease status.
Phase 1b cohort
PTX-100 is a first-in-class drug candidate which works by disrupting the oncogenic Ras pathway by inhibiting the activation of Rho, Rac and Ral proteins, leading to the death of cancer cells.
The three patients in the phase 1b study cohort were heavily pre-treated and suffered from advanced multiple myeloma, cutaneous T-cell lymphoma and peripheral T-cell lymphoma – all of which have been previously classed as difficult to treat.
The patients received 500mg/m2 doses of PTX100 with no drug-related safety issues observed.
Based on the observations, the study’s safety monitoring committee has allowed the PTX-100 trial to proceed to a dose of 1,000mg/m2.
Patients will receive the drug by intravenous infusion over 60 minutes on days one-to-five of a 14-day cycle, for four cycles unless toxicity is observed.
The aim is to identify the optimal time and dose-dependent effect of multiple doses of the drug.
Prescient is seeking to identify the mutational status of each patient’s malignancies and, within the constraints of a small sample size, seek to correlate this status with any clinical activity.
Several cancer biomarkers will be investigated with the aim of identifying patients who could be most likely to respond to PTX-100 therapy.
New trial site
The next phase of Prescient’s trial has been expanded to include specialist oncology practice PASO Medical, located in south-eastern Victoria.
The company expects PASO’s focus on solid tumours will complement the haematological cancer expertise at Epworth Hospital, and increase the diversity of cancer types recruited to the PTX-100 study.
Prescient managing director Steven Yatomi-Clarke said the PTX-100 dose escalation was a promising development.
“We are delighted with the safety profile in the first cohort which has led to a dose escalation of PTX-100, especially in heavily pre-treated patients with advanced cancers,” he said.
“The Ras pathway has been in focus over the last 12 months, receiving much attention from medical and pharmaceutical communities, and we believe the outcomes of this study – especially as a unique, first-in-class inhibitor of this pathway – will warrant attention.”
At midday, shares in Prescient were trading 11.43% higher at $0.039.