Kintor Pharmaceutical Limited (“Kintor Pharma”, HKEX: 9939), a clinical-stage biotechnology company developing innovative small molecules and biological therapeutics, today announced that the results from a phase Ib study of pruxelutamide (used to be called proxalutamide, GT0918) for the treatment of patients with androgen receptor positive (AR+) metastatic breast cancer (AR+ mBC) in China have been published in the international journal, European Journal of Cancer (2021 Impact Factor: 10.002, EJC) on September 28, 2022, further demonstrating the efficacy and safety of pruxelutamide in patients with AR+ mBC.
Highlights
Pruxelutamide showed promising activity in heavily pretreated AR+ mBC patients.
Pruxelutamide showed an acceptable safety profile in heavily pretreated AR+ mBC.
Recommended phase II dose of pruxelutamide was defined as 200mg orally once daily.
AR expression, cell-free DNA yield, CNV might be associated with response.
Patients with PIK3CA pathogenic mutation showed longer progression-free survival.
Metastatic breast cancer (mBC) remains a largely incurable disease in most patients, resulting in approximately 0.5 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.
Pruxelutamide is an oral, newly-generation AR antagonist, developed by Kintor Pharma. 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 multicentre phase Ib study and biomarker analysis”. This phase Ib study was designed to evaluate the preliminary efficacy and safety of pruxelutamide monotherapy in patients with pretreated AR+ mBC and to determine the RP2D of pruxelutamide. The corresponding author of the paper, Professor Huiping Li of Peking University Cancer Hospital & Institute, was the principal investigator of the phase I clinical trial in China.
In this open-label, dose-expansion, multicentre phase Ib trial, patients with AR+ mBC (immunohistochemistry [IHC] AR≥1%) 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 II 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% (95% confidence interval [CI], 11.9–39.4%), with 26.9% in cohort A and 23.1% in cohort B. The 6-month progression-free survival (PFS) rate was 19.6% (95% CI, 10.2–37.5%). In the triple-negative subgroup, DCR at 8 weeks was 38.5%, with median PFS of 9.1 months (95% CI, 7.8–NA) in those who achieved response at 8 weeks (n = 5).
All 45 patients were evaluable for safety. Overall, pruxelutamide demonstrated a good safety profile. The most common grade 3 or 4 AEs were 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 IHC (26%–75%), PIK3CA pathogenic mutations, or <60 ng/ml cell-free DNA yield showed longer PFS.
In conclusion, pruxelutamide demonstrated promising anti-tumour 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. Furthermore, we identified that AR expression, CNVs, and cfDNA yield may be associated with the response to pruxelutamide, highlighting the importance of conducting genomic profiling in patients with AR+ mBC to identify those likely to benefit from pruxelutamide treatment. The data supports further clinical development of pruxelutamide on treating breast cancer patients.
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