The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JBI-802 in patients with Advanced Solid Tumors.The efficacy of the RP2D will be evaluated in phase 2 in patients with solid tumors of neuroendocrine differentiation.
This is a multi-center, first in human, open-label, 2-part, dose escalation and expansion study to define safety, tolerability, maximum tolerated dose, pharmacologically active dose, assess preliminary efficacy, and explore predictive and pharmacodynamic biomarkers in up to 126 participants with advanced solid tumors. Expansion cohorts of participants, treated at the RP2D, with small cell lung cancer (SCLC), neuroendocrine prostate cancer (NEPC), and other neuroendocrine-derived cancers will be enrolled to obtain additional safety and efficacy data. Starting dose will be 10 mg orally once daily, 4 days on and 3 days off cycle.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
126
LSD1/HDAC6 inhibitor
Sarah Cannon Research Institute at HealthOne
Denver, Colorado, United States
COMPLETEDThe Christ Hospital
Cincinnati, Ohio, United States
RECRUITINGTennessee Oncology, PLLC
Nashville, Tennessee, United States
COMPLETEDMaximum-Tolerated Dose (MTD)
Time frame: 28-day cycle
Investigator-Assessed ORR (Part 2)
Defined as either complete response (CR) or partial response (PR) as defined by RECIST version 1.1
Time frame: Up to 30 days from the last dose of study drug
Incidence of AEs
Characterized overall and by type, seriousness, relationship to study treatment, timing, and severity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time frame: Up to 30 days from the last dose of study drug
Cmax: Maximum Plasma Concentration JBI-802
Defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations.
Time frame: Baseline up to 28 days from the last dose of study drug
Tmax: Time of Maximum Plasma Concentration JBI-802
Defined as the time at which the Cmax occurs.
Time frame: Baseline up to 28 days from the last dose of study drug
Clast: Last Observed (quantifiable) Plasma Concentration in units of ng/mL JBI-802
Last Observed (quantifiable) Plasma Concentration in units of ng/mL JBI-802
Time frame: Baseline up to 28 days from the last dose of study drug
AUC(0-last): Area Under the Concentration-time Curve from Dosing (time 0) to Time of Last Measured Concentration JBI-802
AUCs will be reported in units of h×ng/mL
Time frame: Baseline up to 28 days from the last dose of study drug
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NEXT Virginia, LLC
Fairfax, Virginia, United States
COMPLETEDAUC(0-t) (partial AUC): Area Under the Concentration-time Curve from Dosing (time 0) to Time t JBI-802
May be computed for one or more values of t, with specific values of t determined after observing the data; AUCs will be reported in units of h×ng/mL
Time frame: Baseline up to 28 days from the last dose of study drug
Vd/F: Apparent Volume of Distribution During Terminal Phase (Vz/F) After Oral Administration calculated as (CL/F)/ Ke
Volume will be reported in units of L.
Time frame: Baseline up to 28 days from the last dose of study drug
CL/F: Apparent Oral Clearance (CL/F) computed as Dose/AUC
Clearance will be reported in units of L/h.
Time frame: Baseline up to 28 days from the last dose of study drug
t½: The Apparent Terminal Elimination Half-life JBI-802
The time required for the drug concentration to decrease by a factor of one-half in the terminal phase. t½ can be estimated as ln(2) / Ke. t1/2 will be reported in units of h.
Time frame: Baseline up to 28 days from the last dose of study drug
Investigator-Assessed Overall Response Rate (ORR) (Part 1)
ORR is defined as the percentage of patients with a confirmed complete response (CR) or a partial response based on RECIST 1.1
Time frame: Up to 30 days from the last dose of study drug
Duration of Response (DOR)
Time from the date of first documented CR or PR, assessed by the investigator and based on RECIST 1.1 to the documented date of progressive disease (PD) or death, whichever occurred first
Time frame: Up to 30 days from the last dose of study drug
PFS: Progression Free Survival
The time from the date the patient started study drug to the date the patient experiences an event of disease progression
Time frame: Date patient started study drug to date of progression, assessed up to 30 months
OS: Overall Survival
The time from the date patient started study drug to death for any reason
Time frame: Date patient started study drug to date of death for any cause, assessed up to 30 months
PSA 50 Response Rate in Patients with Prostate Cancer
The percentage of patients who experience a ≥50% decline in PSA from baseline.
Time frame: Baseline up to 30 days from the last dose of study drug