Prescient Therapeutics’ (ASX: PTX) clinical trial of its PTX-200 drug in breast cancer patients taking the chemotherapy drug paclitaxel has doubled the overall response rate to 50% and eradicated cancer in two patients with advanced disease.
The doubled response rate compares to the industry average of 25% with paclitaxel alone.
Prescient chief executive Steven Yatomi-Clarke welcomed the result from the phase 1b study, saying it was the company’s “most significant clinical milestone to date”.
“We are very encouraged with the results from the phase 1b study, albeit from a relatively small number of patients.
“While the overall results were pleasing, it was particularly encouraging to see our best responses in women with ER-positive disease, which is an especially difficult disease to treat, and with poor expected outcomes from current chemotherapy regimes alone.”
The early-stage trial was carried out with 28 women suffering from human epidermal growth factor receptor 2-negative breast cancer, including estrogen receptor negative/progesterone receptor negative (triple negative) and ER-positive breast cancers.
An initial cohort of 16 patients reached dose-escalation during the phase 1b stage of the trial conducted in the US at Albert Einstein College of Medicine in New York (Montefiore Cancer Center), under the guidance of well-regarded breast cancer specialist Prof Joseph Sparano, and at H. Lee Moffitt Cancer Center.
The trial was expanded to include 12 more patients with locally advanced or metastatic HER2-negative breast cancer. These patients received the recommended phase 2 dose of 35 mg/m of PTX-200, together with 80mg/m/week of paclitaxel, followed by standard doxorubicin-cyclophosphamide and surgery for locally advanced disease. Ten patients were evaluable to assess for their clinical response, with five patients having locally advanced disease and five experiencing metastatic disease.
The overall response rate was made up of complete and partial responses to drug therapy, with complete response defined as full eradication of cancer, while partial response refers to an incomplete eradication of the patient’s cancer.
Prescient cited studies from GN Hortobagyi and his colleagues in the Journal of Clinical Oncology and Professor Sparano and his fellow researchers in two Breast Cancer Research and Treatment journal articles to affirm the expected industry average for a response from weekly chemotherapy would produce a complete recovery rate of 8-48% for all subtypes.
Similarly, Prescient’s survey of the same research found the typical complete recovery rate for locally advanced ER-positive HER2-negative breast cancer was 16% (11-22%), while their overall response rate was 25%.
Of the 10 evaluable women from Prescient’s study, two ER-positive women experienced a pathological complete response, but none of the triple negative women experienced full recovery, taking the complete recovery rate to 20%.
Four women in the evaluable group were ER-positive and six were triple negative.
One ER-positive woman experienced partial recovery, and two triple-negative patients also had partial response, putting the partial response rate at 30%.
The combined overall response rate — both recovered and partially recovered — for the women was an encouraging 75% for the three ER-positive women and 33% for the two triple-negative patients, to deliver the overall result of 50% for the study.
Returning the evaluable group’s results, another ER-positive woman was judged as having stable disease — no progression, but no reduction, while two more triple-negative patients were also classified as stable, placing the stable disease rate at 30%.
No ER-positive woman experienced progressive disease, while two women from the triple-negative group experienced the disappointing response, putting the study’s progressive disease rate at 20%.
Five patients from the phase 1b study who have progressed to the phase 2 study have been qualified to be assessed for the phase 2 data.
The phase 2 trial in 26 patients will use a two-stage Simons MinMax design. If at least three complete recoveries are observed in the first 11 patients, then the phase 2 trial expands to include another 15 patients. For the purposes of this analysis, two complete recoveries have already been observed in the first five patients.
PTX-200 and other studies
Prescient’s early stage therapeutic PTX-200 is its leading drug candidate. It works by inhibiting the Akt tumour survival pathway, which plays a role in breast and ovarian cancer and leukaemia.
Prescient describes its Akt inihibitor as relatively safe when compared to other a number of known non-specific kinase inhibitors that have toxicity problems.
Three studies are under way for the PTX-200 compound. They include the phase 2 trial in breast cancer patients at Montefiore and the Moffitt, a phase 1b/2 trial in in acute myeloid leukemia in the US under the guidance of Prof Jeffrey Lancet, and another phase 1b/2 trial, in combination with current standard of care, in patients with recurrent or persistent platinum resistant ovarian cancer at the Moffitt.