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

• Sponsor: Hinova Pharmaceuticals Aus Pty Ltd (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05252364
• Collaborator: (none)
• Enrollment: 30
• Locations: 5
• Arms: 7
• Anticipated Duration (Months): 26.5
• Patients Per Site: 6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: HP518 - Dose Escalation; Drug: HP518 - Dose expansion	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Dec 14, 2021
• Anticipated Primary Completion Date: Dec 30, 2023
• Anticipated Study Completion Date: Feb 29, 2024

Arms and Interventions

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 1 - Dose Escalation, 50mg/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 100mg/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 200mg/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 300mg/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 400mg/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.
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.

Outcome Measures

Primary Outcome Measures

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 drug [28 days]

   To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

2. 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 and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

3. 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 and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

4. Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [Time Frame: Through study completion, an average of 1 year]

   To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

5. 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 and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

6. Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518. [12 weeks]

Secondary Outcome Measures

1. Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC) [12 weeks]

2. Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax) [12 weeks]

3. Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax) [12 weeks]

4. Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2) [12 weeks]

5. Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) [12 weeks]

6. Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F) [12 weeks]

7. Assessment of PSA50 from baseline to after 4 and 8 weeks of dosing with HP518 [8 weeks]

   To evaluate PSA50 from baseline to after 4 and 8 weeks of dosing with HP518

8. 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) [Through study completion, an average of 1 year]

   To evaluate the time to PSA progression

9. Time to radiographic progression using the RECIST v1.1 and PCWG3 definition [Through study completion, an average of 1 year]

   To evaluate radiographic progression per RECIST v1.1 and PCWG3

10. Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline [Through study completion, an average of 1 year]

    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

11. Change in number of AR N-term-positive CTCs/ml from baseline to week 12 [12 weeks]

12. Genomic profiling using cfDNA [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

1. 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.

2. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).

3. Has significant cardiovascular disease.

4. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Border Medical Oncology	Albury	New South Wales	Australia	2640
2	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
3	Macquarie University	Macquarie Park	New South Wales	Australia	2113
4	Peter McCallum Cancer Center	Melbourne	Victoria	Australia	3000
5	Alfred Hospital	Melbourne	Victoria	Australia	3181

Sponsors and Collaborators

• Hinova Pharmaceuticals Aus Pty Ltd

Investigators

• Study Director: Zhonghua Zhou, Hinova Pharmaceuticals USA, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hinova Pharmaceuticals Aus Pty Ltd
• ClinicalTrials.gov Identifier: NCT05252364
• Other Study ID Numbers: HP518-CS-001
• First Posted: Feb 23, 2022
• Last Update Posted: May 6, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

No Results Posted as of May 6, 2022