China-based Kintor Pharmaceutical Ltd (HKG: 9939) has published the latest data from a Phase Ic clinical study evaluating its proxalutamide in combination with endocrine therapies (ETs) for metastatic breast cancer. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2023, shedding light on the drug’s potential in this challenging cancer indication.
Study Details and Outcomes
Conducted from June 2019 to September 2022, the study involved 37 patients divided into two parts. Among those receiving proxalutamide combined with fulvestrant, seven patients achieved partial response (PR), and 11 experienced stable disease (SD). The objective response rate (ORR) was 20% in cohort C and 25.0% in cohort D. The overall disease control rate (DCR) reached 50% in cohort C and 65% in cohort D. Median progression-free survival (PFS) was 6.4 months for cohort C and 7.4 months for cohort D.
Pharmacokinetics and Safety Profile
The pharmacokinetic (PK) curve indicated that proxalutamide is rapidly absorbed after a single dose administration, with serum concentration levels reaching a steady state by the 29th day of multiple dosing, showing a trend of drug accumulation. Importantly, no dose-limiting toxicity (DLT) or serious adverse events (SAEs) were reported. The most common level 3 treatment-emergent adverse events (TEAEs) included a decrease in neutrophil count, hypokalemia, and bone marrow suppression, each at 8.1% (3/37).
Proxalutamide’s Mechanism and Clinical Potential
Proxalutamide is a second-generation androgen receptor (AR) antagonist developed by Kintor, featuring a dual mechanism of action that suppresses AR activity through direct antagonism and by downregulating AR expression. Preclinical studies have demonstrated the efficacy of combining AR antagonists with ETs against various estrogen receptor positive (ER+)/androgen receptor positive (AR+) breast cancer cell lines. A Phase Ia clinical study showed approximately 25% clinical benefit and good safety in metastatic breast cancer patients who had failed multi-line treatment after receiving proxalutamide.-Fineline Info & Tech
