Evaluation of Safety and Efficacy of KPG-121 Plus Enzalutamide, Abiraterone or Apalutamide in CRPC Patients

Castration-Resistant Prostate Cancer Clinical Trial

Official title:

A First-in-Human Study to Determine the Safety, Pharmacokinetics and Efficacy of KPG-121 When Administered With Enzalutamide, Abiraterone, or Apalutamide in Subjects With Non-Metastatic or Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03569280
• Other study ID #: KPG-121-101
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2019
• Est. completion date: June 15, 2023

Study information

• Verified date: July 2023
• Source: Kangpu Biopharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1, open-label, multicenter study of KPG-121 administered orally once daily (QD) in 28-day treatment cycles to adult subjects.

Description:

This Phase 1 study will comprise two parts: Part 1 will be a 3+3 dose escalation design to characterize the MTD and a RP2D, Part 2 will be an expansion cohort at RP2D.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 15, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent provided prior to any study-related procedure being performed;

2. Able to swallow and retain orally administered medication;

3. Male aged 18 years and older;

4. diagnosis of prostate carcinoma;

5. Men with either non-metastatic or metastatic CRPC are eligible;

6. Completed at least 4 or more weeks of prior continuous therapy with fixed stable dose enzalutamide, abiraterone or apalutamide prior to initiating study treatment (for Part 1), or with fixed stable dose enzalutamide (for Part 2), with no change in dose for at least 2 weeks prior to screening;

7. Serum testosterone level <50 ng/dL (<0.5 ng/mL, <7.0 nmol/L).

8. ECOG performance status of 0 or 1;

9. Adequate baseline organ function;

10. Must have a QT interval corrected for heart rate according to Fridericia's formula (QTcF) <470 milliseconds (msec) or <480 msec with bundle branch block;

11. Male subject with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of screening until 3 months after the last dose of study medication;

12. Willing and able to comply with all protocol required visits and assessments.

Exclusion Criteria:

1. Prior chemotherapy, radiation;

2. Prior malignancy other than CRPC.

3. Uncontrolled hypothyroidism, or TSH >2.0 x ULN at screening.

4. Current use of or anticipated requirement of prohibited medication(s);

5. Any unresolved =grade 2 (per CTCAE v5.0) toxicity from previous anti-cancer therapy;

6. Previous history of difficulty swallowing capsules;

7. Known active infection requiring intravenous (IV);

8. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test ;

9. History of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months prior to the start of study medication;

10. Poorly controlled hypertension;

11. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs

12. History or evidence of cardiovascular risk; known cardiac metastases;

13. Previous major surgery within 30 days prior to the start of study medication;

Related Conditions & MeSH terms

• Castration-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Combination Product:
• Enzalutamide or Abiraterone or Apalutamid
Antitumor treatment

Locations

Country	Name	City	State
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	North Shore Hematology Oncology Associates DBA NY Cancer and Blood Specialists	Port Jefferson Station	New York

Sponsors (1)

Lead Sponsor	Collaborator
Kangpu Biopharmaceuticals, Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of KPG-121	MTD is one dose level below the dose level that results in =33% of subjects with a DLT	Cycle-1 (28-day)
Secondary	Incidence of Adverse Events [Safety and Tolerability]	Treatment-Emergent Adverse events	Up to Cycle-6 (28-day per cycle)
Secondary	Pharmacokinetic (PK) profile of KPG-121	Plasma concentrations of KPG-121	Cycle-1 (up to 28-day)