Results from a phase 1b study of a drug to treat patients with androgen receptor positive (AR+) metastatic breast cancer (mBC) in China were published yesterday (September 28).
Kintor Pharmaceutical Limited, a clinical stage biotech company has developed Pruxelutamide, an oral new generation AR antagonist which has shown promising activity in heavily pretreated AR+ mBC patients.
The results were published in the international journal, European Journal of Cancer further demonstrating the efficacy and safety of the drug, Kintor Pharmaceutical says.
Acceptable safety profile for Kintor Pharmaceutical’s pruxelutamide
Other highlights included pruxelutamide showed an acceptable safety profile in heavily pretreated AR+ mBC, that the recommended phase 2 dose of the drug was defined as 200 mg orally once a day and that patients with PIK3CA pathogenic mutation showed longer progression-free survival.
Kintor Pharmaceutical says that metastatic breast cancer (mBC) remains a largely incurable disease in most patients, resulting in approximately half a million deaths every year worldwide. At present, the primary goals of mBC therapy are to prolong patient survival and maintain their quality of life. Any novel therapy likely to provide a survival advantage in patients is valuable.
Kintor Pharmaceutical’s results from this study of pruxelutamide were published in a paper titled “Proxalutamide in patients with AR-positive metastatic breast cancer: Results from an open-label multicenter phase 1b study and biomarker analysis“. This phase 1b study was designed to evaluate the preliminary efficacy and safety of pruxelutamide monotherapy in patients with pretreated AR+ mBC and to determine the RP2D (usually the highest dose with acceptable toxicity, usually defined as the dose level producing around 20% of dose-limiting toxicity) of pruxelutamide.
In this open-label, dose-expansion, multicenter phase 1b trial, patients with AR+ mBC received pruxelutamide orally once daily. Two pruxelutamide dose cohorts (cohort A: 200mg; cohort B: 300mg) were sequentially investigated. Primary endpoints were disease control rate (DCR) at 8 and 16 weeks and recommended phase 2 dose (RP2D).
Finally, 45 eligible patients were enrolled and treated. 30 eligible patients were enrolled in cohort A (200mg orally once daily) from April 19, 2018, to March 7, 2019. 15 patients were enrolled into cohort B (300mg orally once daily) from March 11, 2019, to April 16, 2019.
Among 39 evaluable patients, DCR at 8 and 16 weeks was 25.6% with 26.9% in cohort A and 23.1% in cohort B. The six-month progression-free survival (PFS) rate was 19.6%. In the triple-negative subgroup, DCR at 8 weeks was 38.5%, with median PFS of 9.1 months (five patients) in those who achieved response at 8 weeks.
Good safety profile
All 45 patients were evaluable for safety. Overall, pruxelutamide demonstrated a good safety profile. The most common grade 3 or 4 adverse events were aspartate transaminase (AST) increase (8.9%) and γ-glutamyltransferase increase (8.9%). No treatment-related deaths or dose reductions occurred in either cohort.
This study conducted another exploratory analysis to identify potential predictive biomarkers of treatment response. By biomarker analysis, patients with moderate AR expression of immunohistochemistry (IHC) (26%–75%), PIK3CA pathogenic mutations, or less than 60 ng/ml cell-free DNA yield showed longer PFS.
In conclusion, Kintor Pharmaceutical’s pruxelutamide demonstrated promising anti-tumor activity with an acceptable safety profile in patients with heavily pretreated AR+ mBC, particularly in the TNBC subgroup. And, this study determined the RP2D to be 200mg orally once daily.