Hengrui lately announced positive interim data of a multicenter, randomized, and controlled Phase III study (Study ID Number: SHR-3680-III-HSPC), showing that SHR3680 plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS), the primary endpoint evaluated by Independent Data Monitoring Committee (IDMC), compared with standard of care (SoC) plus ADT in mHSPC patients with high-volume disease burden. The interim analysis demonstrated that SHR3680 significantly reduced the risk of disease progression or death in mHSPC patients with high-volume disease burden. Hengrui will soon submit a pre-new drug application (pre-NDA) meeting request to National Medical Products Administration (NMPA).

About the Study

SHR-3680-III-HSPC is a Phase III, multicenter, randomized, and controlled clinical trial evaluating SHR3680 in combination with ADT in mHSPC patients with high-volume disease burden, compared with SoC in combination with ADT. The study enrolled 654 patients who were randomized 1:1 to receive either SHR3680 plus ADT or SoC plus ADT from 50 sites in China and 22 sites in East Europe (Portland, Czech Republic, and Bulgaria). This study was initiated in June 2018, and Professor Dingwei Ye from Fudan University Shanghai Cancer Center is the Leading Principal Investigator. The primary endpoints include rPFS based on IDMC evaluation and overall survival (OS). The secondary endpoints include rPFS based on Investigator evaluation, time to prostate specific antigen (PSA) progression, safety-related endpoints and etc.

About Prostate Cancer

Prostate cancer is the second most common type of cancer in men and is the fifth leading cause of cancer mortality worldwide. According to the GLOBOCAN 2020 report, there were approximately 1.41 million new prostate cancer cases (comprising 14.1% of male cancer new diagnoses, after lung cancer which accounts for 14.3%) and approximately 380,000 prostate cancer deaths (comprising 6.8% of male cancer deaths) worldwide in 2020. The incidence of prostate cancer in China is significantly lower than that in Western countries, but it has significantly increased in recent years. In 2015, there were approximately 60,000 new prostate cancer cases and approximately 27,000 prostate cancer deaths in China. However, in 2020, there were approximately 115,000 new prostate cancer cases and approximately 51,000 prostate cancer deaths in China, according to World Health Organization.

The growth of prostate cancer cells is androgen-dependent, and therefore newly diagnosed metastatic prostate cancer is sensitive to ADT treatment (i.e., mHSPC). Recent studies showed that novel androgen receptor (AR) antagonist in combination with ADT could be used to treat mHSPC, which could effectively reduce the risk of disease progression or death and prolong OS. This study started in June 2018. At that time, there was no novel AR antagonist approved to treat mHSPC in China.

About SHR3680

SHR3680 is a proprietary novel AR antagonist developed by Hengrui Pharmaceuticals. SHR3680 has much stronger inhibition of AR and no agonistic effect compared with the first generation of AR inhibitors. In 2018, it was supported by the Major New Drug Creation Project of the National Ministry of Science and Technology, and is currently in the late stage of clinical development. SHR3680 demonstrated significantly lower extent of brain penetration in pre-clinical studies, which potentially reduces the risks for seizure.

In addition to the SHR-3680-III-HSPC study which showed positive interim rPFS analysis results, there are multiple phase II clinical studies ongoing to investigate single agent or combination with other drugs (such as docetaxel) in metastatic castration-resistant prostate cancer.