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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Combination Product: Enzalutamide or Abiraterone or Apalutamid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent provided prior to any study-related procedure being performed; Able to swallow and retain orally administered medication; Male aged 18 years and older; diagnosis of prostate carcinoma; Men with either non-metastatic or metastatic CRPC are eligible; 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; Serum testosterone level <50 ng/dL (<0.5 ng/mL, <7.0 nmol/L). ECOG performance status of 0 or 1; Adequate baseline organ function; 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; 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; Willing and able to comply with all protocol required visits and assessments. Exclusion Criteria: Prior chemotherapy, radiation; Prior malignancy other than CRPC. Uncontrolled hypothyroidism, or TSH >2.0 x ULN at screening. Current use of or anticipated requirement of prohibited medication(s); Any unresolved ≥grade 2 (per CTCAE v5.0) toxicity from previous anti-cancer therapy; Previous history of difficulty swallowing capsules; Known active infection requiring intravenous (IV); Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test ; 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; Poorly controlled hypertension; Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs History or evidence of cardiovascular risk; known cardiac metastases; Previous major surgery within 30 days prior to the start of study medication;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: KPG-121 Plus Enzalutamide or Abiraterone or Apalutamid
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KPG-121<br>Safety and Antitumor Activity of KPG-121 capsules at different dose level for 21 days | Combination Product: Enzalutamide or Abiraterone or Apalutamid<br>* Antitumor treatment<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KPG-121, Enzalutamide, Abiraterone, Apalutamide, Non-metastatic and Metastatic Prostate Cancer