Metastatic Castration-resistant Prostate CancerPhase 1NCT05252364
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 study testing HP518 - Dose Escalation and HP518 - Dose expansion in people with Metastatic Castration-resistant Prostate Cancer, run by Hinova Pharmaceuticals Aus Pty Ltd at 5 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- HP518 - Dose Escalation and HP518 - Dose expansion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesAustralia
- Study dates
- 14 Dec 2021to 22 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Australia5 sites
Border Medical Oncology
Albury, New South Wales, 2640
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Macquarie University
Macquarie Park, New South Wales, 2113
Peter McCallum Cancer Center
Melbourne, Victoria, 3000
Alfred Hospital
Melbourne, Victoria, 3181
About this study
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
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.
Read the 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.
- Being tested
- HP518 - Dose Escalation, HP518 - Dose expansion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HP518 - Dose EscalationDrug
Part 1: Dose escalation
Daily oral dosage with the prescribed dose level based on Cohort assignment.
HP518 - Dose expansionDrug
Part 2: Dose expansion
Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 - Dose Escalation, 25mg/d (Cohort 1) | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose Escalation |
| Part 1 - Dose Escalation 100mg/d (Cohort 2) | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose Escalation |
| Part 1 - Dose Escalation 200mg/d (Cohort 3) | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose Escalation |
| Part 1 - Dose Escalation 300mg/d (Cohort 4) | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose Escalation |
| Part 1 - Dose Escalation 400mg/d (Cohort 5) | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose Escalation |
| Part 1 - Dose Escalation 500mg/d (Cohort 6) | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose Escalation |
| Part 2 - Dose Expansion | Experimental | Oral tablet(s), once daily in 28-day cycles Receives: Drug: HP518 - Dose expansion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 12 weeks
Secondary outcomes (12)
Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)
Measured: 12 weeks
Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)
Measured: 12 weeks
Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)
Measured: 12 weeks
Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)
Measured: 12 weeks
Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Measured: 12 weeks
Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Through study completion, an average of 1 year
Change in number of AR N-term-positive CTCs/ml from baseline to week 12
Measured: 12 weeks
Genomic profiling using cfDNA
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2022
- Study start14 Dec 2021
- Primary completion22 Jan 2024
- Study completion22 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hinova Pharmaceuticals Aus Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zhonghua Zhou, Study director, Hinova Pharmaceuticals USA, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05252364
- Sponsor's protocol ID
- HP518-CS-001
- Status last verified
- Mar 2024
- First submitted
- 3 Dec 2021
- Last updated
- 21 Mar 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40289067
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05252364
- Acronym / sponsor ID
- HP518-CS-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Hinova Pharmaceuticals Aus Pty LtdIndustry (pharma, biotech, devices)
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- 22 Jan 2024 (actual)
- Study completion
- 22 Jan 2024 (actual)
- First posted
- 23 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part 1 - Dose Escalation, 25mg/d (Cohort 1) | Experimental | Drug: HP518 - Dose EscalationOral tablet(s), once daily in 28-day cycles |
| Part 1 - Dose Escalation 100mg/d (Cohort 2) | Experimental | Drug: HP518 - Dose EscalationOral tablet(s), once daily in 28-day cycles |
| Part 1 - Dose Escalation 200mg/d (Cohort 3) | Experimental | Drug: HP518 - Dose EscalationOral tablet(s), once daily in 28-day cycles |
| Part 1 - Dose Escalation 300mg/d (Cohort 4) | Experimental | Drug: HP518 - Dose EscalationOral tablet(s), once daily in 28-day cycles |
| Part 1 - Dose Escalation 400mg/d (Cohort 5) | Experimental | Drug: HP518 - Dose EscalationOral tablet(s), once daily in 28-day cycles |
| Part 1 - Dose Escalation 500mg/d (Cohort 6) | Experimental | Drug: HP518 - Dose EscalationOral tablet(s), once daily in 28-day cycles |
| Part 2 - Dose Expansion | Experimental | Drug: HP518 - Dose expansionOral tablet(s), once daily in 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HP518 - Dose EscalationPart 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort assignment. | Drug | 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 expansionPart 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1. | Drug | Part 2 - Dose Expansion |
Primary outcome
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
Time frame: 28 days
To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)
Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness
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)
Incidence of laboratory 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)
Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
Time frame: 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)
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
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)
Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518.
Time frame: 12 weeks
12 secondary outcomes
Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)
Time frame: 12 weeks
Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)
Time frame: 12 weeks
Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)
Time frame: 12 weeks
Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)
Time frame: 12 weeks
Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: 12 weeks
Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)
Time frame: 12 weeks
Assessment of PSA50 from baseline to after 4 and 8 weeks of dosing with HP518
Time frame: 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)
Time frame: Through study completion, an average of 1 year
Time to radiographic progression using the RECIST v1.1 and PCWG3 definition
Time frame: Through study completion, an average of 1 year
Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline
Time frame: Through study completion, an average of 1 year
Change in number of AR N-term-positive CTCs/ml from baseline to week 12
Time frame: 12 weeks
Genomic profiling using cfDNA
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2024.
- Derived from this study: PubMed 40289067Azad 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.
- Individual participant dataSharing planned: No
Related trials for Metastatic Castration-resistant Prostate Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhonghua Zhou study director
Hinova Pharmaceuticals USA, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HP518 - Dose Escalation and HP518 - Dose expansion in people with Metastatic Castration-resistant Prostate Cancer, run by Hinova Pharmaceuticals Aus Pty Ltd at 5 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 drug (time frame: 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05252364, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2024.