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

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

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.

Study Overview

• Status: Completed
• Conditions: Castration-Resistant Prostate Cancer
• Intervention / Treatment: Combination product: Enzalutamide or Abiraterone or Apalutamid

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: YONG GUO, MD; Phone Number: 1-732-910-5945; Email: yong.guo@kangpugroup.com

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Port Jefferson Station, New York, United States, 11776
      • North Shore Hematology Oncology Associates DBA NY Cancer and Blood Specialists
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KPG-121; Safety and Antitumor Activity of KPG-121 capsules at different dose level for 21 days	Combination product: Enzalutamide or Abiraterone or Apalutamid; Antitumor treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events [Safety and Tolerability]	Treatment-Emergent Adverse events	Up to Cycle-6 (28-day per cycle)
Pharmacokinetic (PK) profile of KPG-121	Plasma concentrations of KPG-121	Cycle-1 (up to 28-day)

Collaborators and Investigators

• Sponsor: Kangpu Biopharmaceuticals, Ltd.
• Investigators: Study Director: Yao Wang, Kangpu Biopharmaceuticals, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2019
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): June 15, 2023

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 16, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Enzalutamide; Apalutamide; Abiraterone; KPG-121; Non-metastatic and Metastatic Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: KPG-121-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No