A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer

A Phase 1 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer

The overall objective of this Phase 1 study is to evaluate the safety, PK, and anti-tumor activity of 12 weeks of daily oral dosing with HP518 after selecting the RP2D of HP518 based on assessments of multiple dose escalation in patients with progressive mCRPC.

Study Overview

• Status: Completed
• 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 mCRPC is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide necessary information for efficacy analysis in future studies.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Border Medical Oncology
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Macquarie Park, New South Wales, Australia, 2113
      • Macquarie University
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter McCallum Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has histologically confirmed adenocarcinoma of the prostate.
2. Has metastatic disease at study entry documented by 2 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
3. Has disease progression while receiving any ADT, androgen biosynthesis inhibitors, or second-generation AR inhibitors.
4. Must have recovered from toxicities related to any prior treatments
5. Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.
6. ECOG performance status score of 0 to 1.

Exclusion Criteria:

1. Has received more than 1 line of chemotherapy for prostate cancer.

2. Use of enzalutamide, and/or other second-generation AR inhibitors and/or abiraterone as follows:

   • Received any agent within 4 weeks prior to the start of study drug.
   • Discontinued agent without evidence of radiographic or PSA progression.
3. Has had any anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177Lu-PSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518.
4. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
5. Has significant cardiovascular disease.
6. Use of an investigational agent, without evidence of radiographic or PSA progression, within 4 weeks prior to the first dose of HP518 or a period required by local regulation, whichever is longer.

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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Dose Escalation, 25mg/d (Cohort 1); 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 assignment.
Experimental: Part 2 - Dose Expansion; 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.
Experimental: Part 1 - Dose Escalation 100mg/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 assignment.
Experimental: Part 1 - Dose Escalation 200mg/d (Cohort 3); 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 assignment.
Experimental: Part 1 - Dose Escalation 300mg/d (Cohort 4); 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 assignment.
Experimental: Part 1 - Dose Escalation 400mg/d (Cohort 5); 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 assignment.
Experimental: Part 1 - Dose Escalation 500mg/d (Cohort 6); 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 assignment.

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 drug	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 and tolerability and determine the MTD and the RP2D 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 and tolerability and determine the MTD and the RP2D 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 and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	Time Frame: 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 and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518.		12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetic parameters of HP518 : 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: 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 PSA50 from baseline to after 4 and 8 weeks of dosing with HP518	To evaluate PSA50 from baseline to after 4 and 8 weeks of dosing with HP518	8 weeks
Time to PSA progression using the PCWG3 definition (PSA >25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart)	To evaluate the time to PSA progression	Through study completion, an average of 1 year
Time to radiographic progression using the RECIST v1.1 and PCWG3 definition	To evaluate radiographic progression per RECIST v1.1 and PCWG3	Through study completion, an average of 1 year
Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline	To assess objective response by RECIST v1.1 (proportion of patients with a PR or CR) in patients with measurable soft tissue disease at baseline	Through study completion, an average of 1 year
Change in number of AR N-term-positive CTCs/ml from baseline to week 12		12 weeks
Genomic profiling using cfDNA		12 weeks

Collaborators and Investigators

• Sponsor: Hinova Pharmaceuticals Aus Pty Ltd
• Investigators: Study Director: Zhonghua Zhou, Hinova Pharmaceuticals USA, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Actual): January 22, 2024
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: HP518-CS-001

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: Yes
• Studies a U.S. FDA-regulated device product: No