Clinical trial NCT05252364: A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Hinova Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-23
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
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
timeFrame: 28 days
measure: Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness
timeFrame: Through study completion, an average of 1 year
measure: Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
timeFrame: Through study completion, an average of 1 year
measure: Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
timeFrame: Time Frame: Through study completion, an average of 1 year
measure: 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
timeFrame: Through study completion, an average of 1 year
measure: Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518.
timeFrame: 12 weeks
Secondary outcomes:
measure: Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)
timeFrame: 12 weeks
measure: Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)
timeFrame: 12 weeks
measure: Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)
timeFrame: 12 weeks
measure: Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)
timeFrame: 12 weeks
measure: Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
timeFrame: 12 weeks
measure: Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)
timeFrame: 12 weeks
measure: Assessment of PSA50 from baseline to after 4 and 8 weeks of dosing with HP518
timeFrame: 8 weeks
measure: 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)
timeFrame: Through study completion, an average of 1 year
measure: Time to radiographic progression using the RECIST v1.1 and PCWG3 definition
timeFrame: Through study completion, an average of 1 year
measure: Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline
timeFrame: Through study completion, an average of 1 year
measure: Change in number of AR N-term-positive CTCs/ml from baseline to week 12
timeFrame: 12 weeks
measure: Genomic profiling using cfDNA
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Albury
country: Australia
facility: Border Medical Oncology
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: Melbourne
country: Australia
facility: Peter McCallum Cancer Center
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
Study officials:
affiliation: Hinova Pharmaceuticals USA, Inc.
name: Zhonghua Zhou
role: STUDY_DIRECTOR
References: