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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06155084
• Other study ID #: HP518-01-01-03
• Status: Recruiting
• Phase: Phase 1
• Start date: December 26, 2023
• Est. completion date: September 2026

Study information

• Verified date: November 2023
• Source: Hinova Pharmaceuticals Inc.
• Contact: Hui Liu
• Phone: +86 28 8505 8465
• Email: HP518[@]hinovapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: September 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• HP518 - Dose Escalation
Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort
• HP518 - Dose Escalation
Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort
• HP518 -Dose Expansion
Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Hinova Pharmaceuticals Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	PSA50 response rate	Proportion of patients showing a PSA decline by =50% between baseline and Week 12 of dosing with HP518.	12 weeks
Secondary	area under the concentration-time curve (AUC)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Secondary	Maximum concentration (Cmax)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Secondary	Time to maximum concentration (Tmax)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Secondary	Apparent terminal elimination half-life (T1/2)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Secondary	apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Secondary	oral clearance (CL/F)	Assessment of pharmacokinetic parameters of HP518	12 weeks
Secondary	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
Secondary	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
Secondary	Time to radiographic progression by investigator PCWG3 definition	using the RECIST v1.1 and PCWG3 definition	Through study completion, an average of 1 year
Secondary	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
Secondary	analyze the efficacy of patients with different AR phenotypes(Part 2)	According to genetic testing results	Through study completion, an average of 1 year