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

Primary Purpose

Metastatic Castration-resistant Prostate Cancer

Status

Active

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

HP518 - Dose Escalation

HP518 - Dose expansion

About this trial

This is an interventional treatment trial for Metastatic Castration-resistant Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Part II (Dose Expansion) patients meeting the following criteria will be excluded from the study:
Expression of androgen receptor splice variant 7 (ARV7), a splice variant subtype of the AR.

Sites / Locations

Border Medical Oncology
Chris O'Brien Lifehouse
Macquarie University
Peter McCallum Cancer Center
Alfred Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Part 1 - Dose Escalation, 25mg/d (Cohort 1)

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 2 - Dose Expansion

Arm Description

Oral tablet(s), once daily in 28-day cycles

Outcomes

Primary Outcome Measures

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)

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)

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)

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)

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)

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

Secondary Outcome Measures

Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)

Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)

Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)

Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)

Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)

Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)

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 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 to radiographic progression using the RECIST v1.1 and PCWG3 definition

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

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

Genomic profiling using cfDNA

Full Information

NCT ID

NCT05252364

First Posted

December 3, 2021

Last Updated

October 19, 2023

Sponsor

Hinova Pharmaceuticals Aus Pty Ltd

1. Study Identification

Unique Protocol Identification Number

NCT05252364

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 14, 2021 (Actual)

Primary Completion Date

March 6, 2024 (Anticipated)

Study Completion Date

March 6, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hinova Pharmaceuticals Aus Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Castration-resistant Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 - Dose Escalation, 25mg/d (Cohort 1)

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Arm Title

Part 1 - Dose Escalation 100mg/d (Cohort 2)

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Arm Title

Part 1 - Dose Escalation 200mg/d (Cohort 3)

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Arm Title

Part 1 - Dose Escalation 300mg/d (Cohort 4)

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Arm Title

Part 1 - Dose Escalation 400mg/d (Cohort 5)

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Arm Title

Part 1 - Dose Escalation 500mg/d (Cohort 6)

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Arm Title

Part 2 - Dose Expansion

Arm Type

Experimental

Arm Description

Oral tablet(s), once daily in 28-day cycles

Intervention Type

Drug

Intervention Name(s)

HP518 - Dose Escalation

Intervention Description

Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort assignment.

Intervention Type

Drug

Intervention Name(s)

HP518 - Dose expansion

Intervention Description

Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.

Primary Outcome Measure Information:

Title

Description

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

Time Frame

28 days

Title

Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness

Description

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

Title

Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

Description

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

Title

Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

Description

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

Title

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

Description

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

Title

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

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)

Time Frame

12 weeks

Title

Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)

Time Frame

12 weeks

Title

Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)

Time Frame

12 weeks

Title

Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)

Time Frame

12 weeks

Title

Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)

Time Frame

12 weeks

Title

Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)

Time Frame

12 weeks

Title

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

Description

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

Time Frame

8 weeks

Title

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)

Description

To evaluate the time to PSA progression

Time Frame

Through study completion, an average of 1 year

Title

Time to radiographic progression using the RECIST v1.1 and PCWG3 definition

Description

To evaluate radiographic progression per RECIST v1.1 and PCWG3

Time Frame

Through study completion, an average of 1 year

Title

Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline

Description

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

Title

Change in number of AR N-term-positive CTCs/ml from baseline to week 12

Time Frame

12 weeks

Title

Genomic profiling using cfDNA

Time Frame

12 weeks

10. Eligibility

Sex

Male

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhonghua Zhou

Organizational Affiliation

Hinova Pharmaceuticals USA, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Border Medical Oncology

City

Albury

State/Province

New South Wales

ZIP/Postal Code

2640

Country

Australia

Facility Name

Chris O'Brien Lifehouse

City

Camperdown

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Facility Name

Macquarie University

City

Macquarie Park

State/Province

New South Wales

ZIP/Postal Code

2113

Country

Australia

Facility Name

Peter McCallum Cancer Center

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3000

Country

Australia

Facility Name

Alfred Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3181

Country

Australia

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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