A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Interventions
- Drug: HP518 - Dose EscalationDrug: HP518 - Dose expansion
- Registration Number
- NCT05252364
- Lead Sponsor
- Hinova Pharmaceuticals Aus Pty Ltd
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 22
- 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.
-
Has received more than 1 line of chemotherapy for prostate cancer.
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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.
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Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
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Has significant cardiovascular disease.
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 - Dose Escalation 100mg/d (Cohort 2) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 1 - Dose Escalation, 25mg/d (Cohort 1) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 1 - Dose Escalation 200mg/d (Cohort 3) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 1 - Dose Escalation 300mg/d (Cohort 4) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 1 - Dose Escalation 400mg/d (Cohort 5) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 1 - Dose Escalation 500mg/d (Cohort 6) HP518 - Dose Escalation Oral tablet(s), once daily in 28-day cycles Part 2 - Dose Expansion HP518 - Dose expansion Oral tablet(s), once daily in 28-day cycles
- Primary Outcome Measures
Name Time Method 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)
Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518. 12 weeks 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)
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)
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)
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)
- Secondary Outcome Measures
Name Time Method 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 8 weeks To evaluate PSA50 from baseline to after 4 and 8 weeks of dosing with HP518
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
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
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
Change in number of AR N-term-positive CTCs/ml from baseline to week 12 12 weeks Genomic profiling using cfDNA 12 weeks 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
Trial Locations
- Locations (5)
Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Border Medical Oncology
🇦🇺Albury, New South Wales, Australia
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Macquarie University
🇦🇺Macquarie Park, New South Wales, Australia
Peter McCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia