A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients

A Phase I/II Open-Label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer in China

The overall objective of this Phase 1 study is to evaluate the safety, PK,and anti-tumor activity of daily oral dosing with HP518,selecting the RP2D of HP518 based on assessments of patients with progressive mCRPC in dose-escalation phase

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: HP518 - Dose Escalation; Drug: HP518 -Dose Expansion

Detailed Description

This First in Human dose escalation and expansion study of HP518 in patients with progressive mCRPC after NHA and chemotherapy is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide preliminary efficacy for the reference of future studies.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qianrong Xiang; Phone Number: +86 28 8505 8465; Email: qrxiang@hinovapharma.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The Second Hospital of Anhui Medical University
      • Principal Investigator: dexin yu
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Cancer Hospital
      • Principal Investigator: Jun Guo
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
      • Principal Investigator: Yinong Niu
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Recruiting
      • Chongqing University Cancer Hospital
      • Principal Investigator: Hong Luo
    • Chongqing, Chongqing Municipality, China
      • Recruiting
      • The Second Affiliated Hospital of Chongqing Medical University
      • Principal Investigator: Xian Yu
      • Principal Investigator: Qing Jiang
  • Fujian
    • Xiamen, Fujian, China
      • Not yet recruiting
      • The First Affiliated Hospital Of Xiamen Univeristy
      • Principal Investigator: Jinchun Xing
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • Lanzhou University Second Hospital
      • Principal Investigator: Li Yang
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • The Third Affiliated Hospital of Southern Medical University
      • Principal Investigator: Cundong Liu
  • Guizhou
    • Guiyang, Guizhou, China
      • Recruiting
      • The Affiliated Hospital of Guizhou Medical University
      • Principal Investigator: Qiang Wang
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Principal Investigator: Tiejun Yang
    • Zhengzhou, Henan, China
      • Recruiting
      • Zhengzhou Central Hospital
      • Principal Investigator: Kai Zhang
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital
      • Principal Investigator: Zhiquan Hu
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
      • Principal Investigator: Shusuan JIANG
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • The First Affiliated Hospital of Nanchang University
      • Principal Investigator: Cheng Zhang
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Liaoning Cancer Hospital & Institute
      • Principal Investigator: Yu Zeng
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Provincial Hospital
      • Principal Investigator: Hao Ning
    • Qingdao, Shandong, China
      • Recruiting
      • The Affiliated Hospital Of Qingdao University
      • Principal Investigator: Haitao Niu
    • Yantai, Shandong, China
      • Recruiting
      • Yantai Yuhuangding Hospital
      • Principal Investigator: Jitao Wu
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Shanghai Tenth People's Hospital
      • Principal Investigator: Xudong Yao
  • Shanxi
    • Xi’an, Shanxi, China
      • Recruiting
      • The First Affiliated Hospital Of Xi'An Jiaotong Univeristy
      • Principal Investigator: Lei Li
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital of Sichuan University
      • Principal Investigator: Ping Feng
      • Principal Investigator: Qiang Dong
    • Chengdu, Sichuan, China
      • Recruiting
      • Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital
      • Principal Investigator: Jing Liu
    • Luzhou, Sichuan, China
      • Recruiting
      • The Affiliated Hospital of Southwest Medical University
      • Principal Investigator: Peng Qing
    • Mianyang, Sichuan, China
      • Recruiting
      • Mianyang Central Hospital
      • Principal Investigator: Xiaobo Du
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • The Second Affiliated Hospital of Kunming Medical University
      • Principal Investigator: Changxing Ke
  • Zhejiang
    • Ningbo, Zhejiang, China
      • Recruiting
      • The Affiliated Hospital Of School Of Medicine Of Ningbo University
      • Principal Investigator: Zejun Yan
    • Wenzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Principal Investigator: Wei Chen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male, age ≥18
2. Patients with androgen receptor (AR) ligand binding domain (LBD) activation mutations (the dose expansion part of stage II)
3. Has histologically confirmed adenocarcinoma of the prostate, but there are no known significant neuroendocrine differentiation or small cell characteristics.
4. Has metastatic disease documented by 2 or more bone lesions by bone scan or soft tissue disease progression observed by CT/MRI at the beginning of study.
5. the progression of the disease after receiving at least one new endocrine therapy and progressing with at least first-line chemotherapy.
6. Must have recovered from toxicities related to any prior treatments
7. Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.
8. ECOG performance status score of 0 to 1.

Exclusion Criteria:

1. Combination of research or commercially available drugs targeting AR
2. Has had any other anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177LuPSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518.
3. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
4. Has significant cardiovascular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Dose Escalation, 400mg/d (Cohort1); Oral tablet(s), once daily in 28-day cycles	Drug: HP518 - Dose Escalation; Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort; Other Names: Part 1 - Dose Escalation
Experimental: Part 1 - Dose Escalation 500mg/d (Cohort 2); Oral tablet(s), once daily in 28-day cycles	Drug: HP518 - Dose Escalation; Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort; Other Names: Part 1 - Dose Escalation
Experimental: Part 2 - Dose Expansion Oral tablet(s); Oral tablet(s), once daily in 28-day cycles	Drug: HP518 -Dose Expansion; Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.; Other Names: Part 2 - Dose Expansion Oral tablet(s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drugorally administered HP518 (Part 1)	To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	28 DAYS
Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness	To evaluate the safety of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing	To evaluate the safety of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing	To evaluate the safety of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Incidence of ECG (PR, QRS, QT, and QTcF intervals) abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing	To evaluate the safety of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
PSA50 response rate	Proportion of patients showing a PSA decline by ≥50% between baseline and Week 12 of dosing with HP518.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under the concentration-time curve (AUC)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Maximum concentration (Cmax)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Time to maximum concentration (Tmax)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Apparent terminal elimination half-life (T1/2)	Assessment of pharmacokinetic parameters of HP518	12 weeks
apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)	Assessment of pharmacokinetic parameters of HP518	12 weeks
oral clearance (CL/F)	Assessment of pharmacokinetic parameters of HP518	12 weeks
According to PCWG3	evaluate PSA50 response rate: PSA decline by≥50% between baseline and 4 weeks/8 weeks/12 weeks( only Part 1) of dosing with HP518	8 weeks
According to PCWG3, evaluate time to PSA progression	PCWG3 definition: PSA increase >25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart) nadir, confirmed by progression at 2 time points at least 3 weeks apart)	Through study completion, an average of 1 year
Time to radiographic progression by investigator PCWG3 definition	using the RECIST v1.1 and PCWG3 definition	Through study completion, an average of 1 year
Evaluate the modified best overall response mBOR by investigator	According to RECIST (version 1.1) and PCWG3	Through study completion, an average of 1 year
analyze the efficacy of patients with different AR phenotypes(Part 2)	According to genetic testing results	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Hinova Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: November 24, 2023
• First Submitted That Met QC Criteria: December 1, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: HP518-01-01-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No