The clinical results of Proclolamide in the treatment of AR+ breast cancer phase Ib were published in the international journal EJC

On September 29, 2022, Beijing time, Pioneer Pharmaceutical (stock code: 9939.
HK), a biopharmaceutical company focusing on the R&D and industrialization of potential first-in-class and best-in-class innovative drugs, announced that the results of its self-developed Proclolamide Phase Ib clinical trial in China in the treatment of androgen receptor-positive (AR+) metastatic breast cancer (mBC) have been published in the international academic journal European Journal of Europe on September 28, 2022 Cancer (2021 Impact Factor 10.
002, EJC) was officially published to further verify the therapeutic potential and safety
of proclolamide in AR+ breast cancer patients.

● Proclolamide shows good antitumor activity
in patients with AR+ mBC who have undergone multi-line therapy.

● Proclolamide has shown a good safety profile
in patients with AR+ mBC who have undergone multi-line therapy.

● The recommended dose of proclolamide phase II clinical trial is 200 mg orally once
daily.

● AR expression levels, cell cell-free DNA (cfDNA) yields, and copy number variation (CNV) may be related to
drug response.

● Patients with a pathogenic mutation of PIK3CA exhibit longer progression-free survival
.

Metastatic breast cancer (mBC) remains a largely incurable disease, killing about 500,000 people worldwide each year
.
Currently, the main goal of mBC treatment is to prolong survival and maintain the patient's quality of life
.
Any new treatment that might provide a survival advantage for patients is valuable
.
Proclolamide is a new generation of AR antagonist
independently developed by Pioneer Pharmaceutical.
The study, published in the journal EJC, is Proxalutamide in patients with AR-positive metastatic breast cancer: Results from an open-label multicentre phase Ib study and biomarker analysis
。 The study was designed to evaluate the initial efficacy and safety of proclolamide monotherapy in patients with AR+ mBC and to determine the recommended dose
for a phase II clinical trial.
The corresponding author of the paper is Professor Li Huiping, Peking University Cancer Hospital, and is the principal investigator of the phase I clinical trial of proclolamide in China for the treatment of AR+ mBC
.

In this open-label, dose-expanded, multicenter Phase Ib clinical trial, patients with AR+ mBC (immunohistochemical [IHC]] AR greater than or equal to 1%) were orally proclolamide
once daily.
This clinical trial looked at two dose cohorts sequentially, Cohort A (200 mg) and Cohort B (300 mg).

Its primary endpoints were disease control rate (DCR) at weeks 8 and 16 and recommended dose (RP2D)
for phase II clinical trials.

The study eventually included 45 patients
.
Thirty patients were enrolled in Cohort A from April 19, 2018 to March 7
, 2019.
Fifteen patients were enrolled in Cohort B from March 11, 2019 to April 16
, 2019.

Results showed that of the 39 evaluable patients, the DCR at weeks 8 and 16 was 25.
6% (95% confidence interval [CI], 11.
9-39.
4%), cohort A 26.
9%, and cohort B 23.
1%.

Progression-free survival (PFS) at six months was 19.
6% (95% CI, 10.
2 to 37.
5%)
.
Notably, in the triple-negative breast cancer subgroup, the DCR was 38.
5% at week 8 and the median PFS in patients who remitted at week 8 (n=5) was 9.
1 months (95% CI, 7.
8-NA).

The study evaluated the safety of all patients (45 patients) who were finally included
.
Overall, proclolamide has a good
safety profile.
The most common grade 3/4 adverse events were elevated aspartate aminotransferase (8.
9%) and elevated Y-glutamyltransferase (8.
9%)
.
No treatment-related deaths or dose reductions
occurred in either cohort.

The study also conducted exploratory biomarker analysis
.
The results showed that patients with moderate expression of IHC AR (26%-75%), carrying PIK3CA pathogenic point mutations, or plasma cfDNA yields of 60 ng/ml showed longer PFS
.

In summary, proclolamide has shown good antitumor activity and safety in patients with AR+ mBC who have undergone multi-line therapy, especially in the triple-negative breast cancer subgroup
.
The study decided that the recommended dose for the phase II clinical trial of proclolamide is 200 mg orally once
daily.
In addition, studies have found that AR expression levels, CNVs, and cfDNA yields may be associated with drug responses, underscoring the importance of
genomic profiling of AR+ mBC patients to identify patients who may benefit from proclolamide therapy.
These results support further clinical studies
.