Clinical trial NCT05268666: A Study of Orally Administered JBI-802, an LSD1/HDAC6 Inhibitor, in Patients With Advanced Solid Tumors
Official title: A First-in-Human, Open-label, Dose Escalation and Expansion Study of Orally Administered JBI-802 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: SCLC
neuroendocrine prostate cancer
neuroendocrine
JBI-802
Lead sponsor: Jubilant Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-07
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Males or females aged ≥18 years at Screening
* Absolute neutrophil count (ANC) ≥1500 cells/mm3.
* Platelet count ≥100,000 cells/mm3.
* Total bilirubin ≤1.5×ULN. Patients with Gilbert's syndrome may be enrolled with up to 3.0xULN.
* AST and ALT ≤2.5×ULN (unless liver metastases are present then up to 5×ULN is allowed).
* Calculated creatinine clearance (CrCL) ≥60 mL/min (Cockcroft-Gault formula).
* Prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN if participant is not anticoagulated (Note: If participant is on anticoagulants, the participant must be on a stable dose for at least 2 weeks prior to study entry.
* Must have at least one measurable lesion on CT scan or MRI per RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
* Other criteria may apply

Part 1:

* Participants with a histologically confirmed diagnosis of locally advanced or metastatic solid tumors (except microsatellite stable colorectal cancer and hepatocellular carcinoma) who have no available effective therapeutic options.

Part 2:

* Small cell lung cancer: Participants must have a histologic diagnosis of advanced SCLC not amenable to curative therapy and have received ≤2 prior regimens, which must have included a checkpoint inhibitor and a platinum-based chemotherapy.
* De novo or treatment-emergent NEPC
* Basket of neuroendocrine-derived tumors, excluding SCLC and treatment-induced NEPC. Participants must have unresectable locally advanced or metastatic disease and have no available effective therapeutic options.

Exclusion Criteria:

* Known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 4 weeks after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of symptomatic brain metastases for at least 14 days prior to enrollment.
* Severe or unstable medical condition, such as congestive heart failure (New York Heart Association \[NYHA\] Class III or Class IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac arrhythmia requiring medication (≥Grade 2, according to NCI CTCAE Version 5), myocardial infarction within 6 months prior to starting study treatment, or any other significant or unstable concurrent cardiac illness. Note: Stable chronic atrial fibrillation is allowed.
* Use of strong inhibitors of CYP3A within 14 days or 5 half-lives (whichever is longer) or grapefruit juice or grapefruit containing products within 7 days prior to Cycle 1 Day 1.
* Use of strong inducers of CYP3A within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
* Use of strong inhibitors of cytochrome CYP2D6 within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
* Use of strong inducers of CYP2D6 within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
* History of other previous or concurrent cancer that would interfere with the determination of safety or efficacy assessment
* Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines
* Other criteria may apply

Primary outcomes:
measure: Maximum-Tolerated Dose (MTD)
timeFrame: 28-day cycle
measure: Investigator-Assessed ORR (Part 2)
timeFrame: Up to 30 days from the last dose of study drug
Secondary outcomes:
measure: Incidence of AEs
timeFrame: Up to 30 days from the last dose of study drug
measure: Cmax: Maximum Plasma Concentration JBI-802
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: Tmax: Time of Maximum Plasma Concentration JBI-802
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: Clast: Last Observed (quantifiable) Plasma Concentration in units of ng/mL JBI-802
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: AUC(0-last): Area Under the Concentration-time Curve from Dosing (time 0) to Time of Last Measured Concentration JBI-802
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: AUC(0-t) (partial AUC): Area Under the Concentration-time Curve from Dosing (time 0) to Time t JBI-802
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: Vd/F: Apparent Volume of Distribution During Terminal Phase (Vz/F) After Oral Administration calculated as (CL/F)/ Ke
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: CL/F: Apparent Oral Clearance (CL/F) computed as Dose/AUC
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: t½: The Apparent Terminal Elimination Half-life JBI-802
timeFrame: Baseline up to 28 days from the last dose of study drug
measure: Investigator-Assessed Overall Response Rate (ORR) (Part 1)
timeFrame: Up to 30 days from the last dose of study drug
measure: Duration of Response (DOR)
timeFrame: Up to 30 days from the last dose of study drug
measure: PFS: Progression Free Survival
timeFrame: Date patient started study drug to date of progression, assessed up to 30 months
measure: OS: Overall Survival
timeFrame: Date patient started study drug to date of death for any cause, assessed up to 30 months
measure: PSA 50 Response Rate in Patients with Prostate Cancer
timeFrame: Baseline up to 30 days from the last dose of study drug
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthOne
state: Colorado
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Fairfax
country: United States
facility: NEXT Virginia, LLC
state: Virginia
Study officials:
affiliation: Jubilant Therapeutics Inc.
name: Program Manager
role: STUDY_DIRECTOR
References: