Clinical trial NCT06155084: A Phase I/II Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Hinova Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-04
Enrollment: 84
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 28 DAYS
measure: Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness
timeFrame: Through study completion, an average of 1 year
measure: Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
timeFrame: Through study completion, an average of 1 year
measure: Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
timeFrame: Through study completion, an average of 1 year
measure: 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
timeFrame: Through study completion, an average of 1 year
measure: PSA50 response rate
timeFrame: 12 weeks
Secondary outcomes:
measure: area under the concentration-time curve (AUC)
timeFrame: 12 weeks
measure: Maximum concentration (Cmax)
timeFrame: 12 weeks
measure: Time to maximum concentration (Tmax)
timeFrame: 12 weeks
measure: Apparent terminal elimination half-life (T1/2)
timeFrame: 12 weeks
measure: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
timeFrame: 12 weeks
measure: oral clearance (CL/F)
timeFrame: 12 weeks
measure: According to PCWG3
timeFrame: 8 weeks
measure: According to PCWG3, evaluate time to PSA progression
timeFrame: Through study completion, an average of 1 year
measure: Time to radiographic progression by investigator PCWG3 definition
timeFrame: Through study completion, an average of 1 year
measure: Evaluate the modified best overall response mBOR by investigator
timeFrame: Through study completion, an average of 1 year
measure: analyze the efficacy of patients with different AR phenotypes(Part 2)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital Of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital Of Chongqing Medical University
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated Hospital Of Xiamen Univeristy
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Southern Medical University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Hospital Of Guizhou Medical University
state: Guizhou
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Central Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanchang
country: China
facility: The First Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital Of Qingdao University
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Xi'An
country: China
facility: The First Affiliated Hospital Of Xi'An Jiaotong Univeristy
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital Of Sichuan University
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital Of Southwest Medical University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Kunming
country: China
facility: The Second Affiliated Hospital Of Kunming Medical University
state: Yunnan
city: Ningbo
country: China
facility: The Affiliated Hospital Of School Of Medicine Of Ningbo University
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: