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

Hinova Pharmaceuticals Aus Pty Ltd22 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Castration-resistant Prostate Cancer

Interventions

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.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (5)

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

Outcomes

Primary Outcomes

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)

Time frame: 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)

Time frame: 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)

Time frame: 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: 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)

Time frame: 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.

Time frame: 12 weeks

Data from ClinicalTrials.gov

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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

To evaluate 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)

To evaluate the time to PSA progression

Time frame: 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

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

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

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