A Phase I/II Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Interventions
- Drug: HP518 - Dose EscalationDrug: HP518 -Dose Expansion
- Registration Number
- NCT06155084
- Lead Sponsor
- Hinova Pharmaceuticals Inc.
- Brief Summary
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
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 84
- Male, age ≥18
- Patients with androgen receptor (AR) ligand binding domain (LBD) activation mutations (the dose expansion part of stage II)
- Has histologically confirmed adenocarcinoma of the prostate, but there are no known significant neuroendocrine differentiation or small cell characteristics.
- 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.
- the progression of the disease after receiving at least one new endocrine therapy and progressing with at least first-line chemotherapy.
- Must have recovered from toxicities related to any prior treatments
- Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.
- ECOG performance status score of 0 to 1.
- Combination of research or commercially available drugs targeting AR
- 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.
- Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
- Has significant cardiovascular disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 - Dose Escalation, 400mg/d (Cohort1) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 1 - Dose Escalation 500mg/d (Cohort 2) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 2 - Dose Expansion Oral tablet(s) HP518 -Dose Expansion Oral tablet(s), once daily in 28-day cycles
- Primary Outcome Measures
Name Time Method Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing Through study completion, an average of 1 year To evaluate the safety of orally administered HP518 (Part 1)
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) 28 DAYS To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness Through study completion, an average of 1 year To evaluate the safety of orally administered HP518 (Part 1)
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 Through study completion, an average of 1 year To evaluate the safety of orally administered HP518 (Part 1)
PSA50 response rate 12 weeks Proportion of patients showing a PSA decline by ≥50% between baseline and Week 12 of dosing with HP518.
Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing Through study completion, an average of 1 year To evaluate the safety of orally administered HP518 (Part 1)
- Secondary Outcome Measures
Name Time Method Apparent terminal elimination half-life (T1/2) 12 weeks Assessment of pharmacokinetic parameters of HP518
apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) 12 weeks Assessment of pharmacokinetic parameters of HP518
oral clearance (CL/F) 12 weeks Assessment of pharmacokinetic parameters of HP518
According to PCWG3 8 weeks evaluate PSA50 response rate: PSA decline by≥50% between baseline and 4 weeks/8 weeks/12 weeks( only Part 1) of dosing with HP518
According to PCWG3, evaluate time to PSA progression Through study completion, an average of 1 year 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)
area under the concentration-time curve (AUC) 12 weeks Assessment of pharmacokinetic parameters of HP518
Maximum concentration (Cmax) 12 weeks Assessment of pharmacokinetic parameters of HP518
Time to maximum concentration (Tmax) 12 weeks Assessment of pharmacokinetic parameters of HP518
Time to radiographic progression by investigator PCWG3 definition Through study completion, an average of 1 year using the RECIST v1.1 and PCWG3 definition
Evaluate the modified best overall response mBOR by investigator Through study completion, an average of 1 year According to RECIST (version 1.1) and PCWG3
analyze the efficacy of patients with different AR phenotypes(Part 2) Through study completion, an average of 1 year According to genetic testing results
Trial Locations
- Locations (27)
The Second Hospital Of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
The Second Affiliated Hospital Of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital Of Xiamen Univeristy
🇨🇳Xiamen, Fujian, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, Gansu, China
The Third Affiliated Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Affiliated Hospital Of Guizhou Medical University
🇨🇳Guiyang, Guizhou, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Zhengzhou Central Hospital
🇨🇳Zhengzhou, Henan, China
Tongji Hospital
🇨🇳Wuhan, Hubei, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital Of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, Liaoning, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
The Affiliated Hospital Of Qingdao University
🇨🇳Qingdao, Shandong, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
Shanghai Tenth People's Hospital
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital Of Xi'An Jiaotong Univeristy
🇨🇳Xi'An, Shanxi, China
Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital
🇨🇳Chengdu, Sichuan, China
West China Hospital Of Sichuan University
🇨🇳Chengdu, Sichuan, China
The Affiliated Hospital Of Southwest Medical University
🇨🇳Luzhou, Sichuan, China
Mianyang Central Hospital
🇨🇳Mianyang, Sichuan, China
The Second Affiliated Hospital Of Kunming Medical University
🇨🇳Kunming, Yunnan, China
The Affiliated Hospital Of School Of Medicine Of Ningbo University
🇨🇳Ningbo, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China