This Phase I study aims to evaluate the safety, tolerability and PK of JSB462 in Japanese patients with metastatic prostate cancer.
Participants will receive JSB462 at the starting dose of 300 mg QD to evaluate its safety, tolerability and PK. Any Adverse Events (AEs) and Dose Limiting Toxicities (DLTs) will be assessed. DLTs will be evaluated in the first (28-day) cycle. If 300 mg once a day (QD) is considered intolerable by investigators and Novartis study personnel during dose evaluation meeting, the tolerability of 100 mg QD dose level cohort may be assessed. Study treatment will be administered until disease progression (per PCWG3-modified RECIST v1.1 assessed by the investigator), unacceptable toxicity, death, withdrawal of consent, lost to follow-up or investigator's decision. The End of Treatment Visit and the Safety Follow-up Visit will be performed within 7 days and 30 days from the last dose of JSB462, respectively. If participants discontinue study treatment for reasons other than disease progression (per PCWG3-modified RECIST v1.1 assessed by the investigator), death, lost to follow-up, or withdrawal of consent, then tumor assessments should continue to be performed in the Efficacy Follow-up Visit according to the planned schedule until disease progression (per PCWG3-modified RECIST v1.1 assessed by the investigator), death, withdrawal of consent or lost to follow-up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
300 mg or 100 mg once a day (QD) with food
Novartis Investigative Site
Nagoya, Aichi-ken, Japan
RECRUITINGNovartis Investigative Site
Bunkyo Ku, Tokyo, Japan
RECRUITINGNovartis Investigative Site
Koto Ku, Tokyo, Japan
RECRUITINGIncidence and severity of dose limiting toxicities (DLTs) during the first cycle of treatment
A dose-limiting toxicity (DLT) is defined as a treatment-related adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the first 28 days of treatment with JSB462 and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose regimen decisions, DLTs will be considered.
Time frame: Up to 28 days
Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Time frame: Through study completion, an average of approximately 18 months
Number of Participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by means of descriptive statistics.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 18 months
Dose Intensity
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics.
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 18 months
Plasma concentrations of JSB462 and its metabolite ARV-767
JSB462 pharmacokinetic (PK) samples will be obtained and evaluated to assess single dose and steady-state plasma Pharmacokinetic (PK) of JSB462 and its metabolite ARV-767 and summarized using descriptive statistics.
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Novartis Investigative Site
Kobe, Japan
RECRUITINGTime frame: Cycle 1: Days 1 & 21 (0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Days 2 & 22 (0 hour). Cycles 2-6: Day 1 (0 hour). End of Treatment Visit (EOT): within 7 days from the last dose of JSB462. 1 cycle = 28 days.
AUC of JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) and Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) will be listed and summarized using descriptive statistics.
Time frame: Cycle 1: Days 1 & 21 (0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Days 2 & 22 (0 hour). Cycles 2-6: Day 1 (0 hour). End of Treatment Visit (EOT): within 7 days from the last dose of JSB462. 1 cycle = 28 days.
Cmax of JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time frame: Cycle 1: Days 1 & 21 (0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Days 2 & 22 (0 hour). Cycles 2-6: Day 1 (0 hour). End of Treatment Visit (EOT): within 7 days from the last dose of JSB462. 1 cycle = 28 days.
Tmax of JSB462
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Time frame: Cycle 1: Days 1 & 21 (0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Days 2 & 22 (0 hour). Cycles 2-6: Day 1 (0 hour). End of Treatment Visit (EOT): within 7 days from the last dose of JSB462. 1 cycle = 28 days.