A Phase I Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients

• Sponsor: Hinova Pharmaceuticals Inc. (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06155084
• Collaborator: (none)
• Enrollment: 62
• Arms: 3
• Anticipated Duration (Months): 33

Study Details

Study Description

Brief Summary

The overall objective of this Phase 1 study is to evaluate the safety, PK,and anti-tumor activity of daily oral dosing with HP518,selecting the RP2D of HP518 based on assessments of patients with progressive mCRPC in dose-escalation phase

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: HP518 - Dose Escalation; Drug: HP518 - Dose Escalation; Drug: HP518 -Dose Expansion	Phase 1

Detailed Description

This First in Human dose escalation and expansion study of HP518 in patients with progressive mCRPC after NHA and chemotherapy is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide preliminary efficacy for the reference of future studies.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 62 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Open-Label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer in China
• Anticipated Study Start Date: Dec 1, 2023
• Anticipated Primary Completion Date: Jul 1, 2026
• Anticipated Study Completion Date: Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 - Dose Escalation, 400mg/d (Cohort1) Oral tablet(s), once daily in 28-day cycles	Drug: HP518 - Dose Escalation; Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort; Other Names: Part 1 - Dose Escalation
Experimental: Part 1 - Dose Escalation 500mg/d (Cohort 2) Oral tablet(s), once daily in 28-day cycles	Drug: HP518 - Dose Escalation; Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort; Other Names: Part 1 - Dose Escalation
Experimental: Part 2 - Dose Expansion Oral tablet(s) Oral tablet(s), once daily in 28-day cycles	Drug: HP518 -Dose Expansion; Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.; Other Names: Part 2 - Dose Expansion Oral tablet(s)

Outcome Measures

Primary Outcome Measures

1. 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 drugorally administered HP518 (Part 1) [28 DAYS]

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

2. 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 of orally administered HP518 (Part 1)

3. 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 of orally administered HP518 (Part 1)

4. Incidence of vital signs 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 of orally administered HP518 (Part 1)

5. 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 of orally administered HP518 (Part 1)

6. PSA50 response rate [12 weeks]

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

Secondary Outcome Measures

1. area under the concentration-time curve (AUC) [12 weeks]

   Assessment of pharmacokinetic parameters of HP518

2. Maximum concentration (Cmax) [12 weeks]

   Assessment of pharmacokinetic parameters of HP518

3. Time to maximum concentration (Tmax) [12 weeks]

   Assessment of pharmacokinetic parameters of HP518

4. Apparent terminal elimination half-life (T1/2) [12 weeks]

   Assessment of pharmacokinetic parameters of HP518

5. apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) [12 weeks]

   Assessment of pharmacokinetic parameters of HP518

6. oral clearance (CL/F) [12 weeks]

   Assessment of pharmacokinetic parameters of HP518

7. According to PCWG3 [8 weeks]

   evaluate PSA50 response rate: PSA decline by≥50% between baseline and 4 weeks/8 weeks/12 weeks( only Part 1) of dosing with HP518

8. According to PCWG3, evaluate time to PSA progression [Through study completion, an average of 1 year]

   PCWG3 definition: PSA increase >25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart) nadir, confirmed by progression at 2 time points at least 3 weeks apart)

9. Time to radiographic progression by investigator PCWG3 definition [Through study completion, an average of 1 year]

   using the RECIST v1.1 and PCWG3 definition

10. Evaluate the modified best overall response mBOR by investigator [Through study completion, an average of 1 year]

    According to RECIST (version 1.1) and PCWG3

11. analyze the efficacy of patients with different AR phenotypes(Part 2) [Through study completion, an average of 1 year]

    According to genetic testing results

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male, age ≥18

2. Patients with androgen receptor (AR) ligand binding domain (LBD) activation mutations (the dose expansion part of stage II)

3. Has histologically confirmed adenocarcinoma of the prostate, but there are no known significant neuroendocrine differentiation or small cell characteristics.

4. Has metastatic disease documented by 2 or more bone lesions by bone scan or soft tissue disease progression observed by CT/MRI at the beginning of study.

5. the progression of the disease after receiving at least one new endocrine therapy and progressing with at least first-line chemotherapy.

6. Must have recovered from toxicities related to any prior treatments

7. Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.

8. ECOG performance status score of 0 to 1.

Exclusion Criteria:

1. Combination of research or commercially available drugs targeting AR

2. Has had any other anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177LuPSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518.

3. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).

4. Has significant cardiovascular disease.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Hinova Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hinova Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT06155084
• Other Study ID Numbers: HP518-01-01-03
• First Posted: Dec 4, 2023
• Last Update Posted: Dec 4, 2023
• Last Verified: Nov 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

No Results Posted as of Dec 4, 2023