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

NCT05252364 | Completed Phase 1 FDA Drug

• 1 other identifier: HP518-CS-001
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (12)

• 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

Study Arms (7)

Part 1 - Dose Escalation, 25mg/d (Cohort 1)

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose Escalation

Part 1 - Dose Escalation 100mg/d (Cohort 2)

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose Escalation

Part 1 - Dose Escalation 200mg/d (Cohort 3)

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose Escalation

Part 1 - Dose Escalation 300mg/d (Cohort 4)

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose Escalation

Part 1 - Dose Escalation 400mg/d (Cohort 5)

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose Escalation

Part 1 - Dose Escalation 500mg/d (Cohort 6)

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose Escalation

Part 2 - Dose Expansion

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: HP518 - Dose expansion

Interventions

HP518 - Dose Escalation DRUG

Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort assignment.

Part 1 - Dose Escalation 100mg/d (Cohort 2); Part 1 - Dose Escalation 200mg/d (Cohort 3); Part 1 - Dose Escalation 300mg/d (Cohort 4); Part 1 - Dose Escalation 400mg/d (Cohort 5); Part 1 - Dose Escalation 500mg/d (Cohort 6); Part 1 - Dose Escalation, 25mg/d (Cohort 1)

HP518 - Dose expansion DRUG

Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.

Part 2 - Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically confirmed adenocarcinoma of the prostate.
• 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.
• Has disease progression while receiving any ADT, androgen biosynthesis inhibitors, or second-generation AR inhibitors.
• 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.

You may not qualify if:

• Has received more than 1 line of chemotherapy for prostate cancer.
• 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.
• 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.
• Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
• Has significant cardiovascular disease.
• 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.

Sponsors & Collaborators

• Hinova Pharmaceuticals Aus Pty Ltd: lead

Study Sites (5)

Border Medical Oncology

Albury, New South Wales, 2640, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Macquarie University

Macquarie Park, New South Wales, 2113, Australia

Location

Peter McCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Related Publications (1)

• Azad AA, Gurney H, Underhill C, Horvath L, Voskoboynik M, Li X, King I, Shao L, Dai Y, Perabo F. Phase 1 study of HP518, a PROTAC AR degrader in patients with mCRPC: results on safety, pharmacokinetics, and anti-tumor activity. Invest New Drugs. 2025 Apr;43(2):435-445. doi: 10.1007/s10637-025-01533-8. Epub 2025 Apr 28.

  PMID: 40289067 DERIVED

Study Officials

• Zhonghua Zhou

  Hinova Pharmaceuticals USA, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: February 23, 2022
• Study Start: December 14, 2021
• Primary Completion: January 22, 2024
• Study Completion: January 22, 2024
• Last Updated: March 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)