A Study of Orally Administered JBI-802, an LSD1/HDAC6 Inhibitor, in Patients With Advanced Solid Tumors

A First-in-Human, Open-label, Dose Escalation and Expansion Study of Orally Administered JBI-802 in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Solid Tumor; Locally Advanced Solid Tumor
• Intervention / Treatment: Drug: JBI-802

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.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chief Scientific Officer; Phone Number: (443) 515-9637; Email: luca.rastelli@jubilanttx.com
• Study Contact Backup: Name: Director, Program Management; Email: rajeev.mohan@jubilanttx.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 82018
      • Completed
      • Sarah Cannon Research Institute at HealthONE
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Completed
      • Tennessee Oncology, PLLC
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Completed
      • NEXT Virginia, LLC

Participation Criteria

Eligibility Criteria

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

Description

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

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: JBI-802; 10 mg JBI-802 once daily as the starting dose with 4 days on/3 days off cycle	Drug: JBI-802; LSD1/HDAC6 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum-Tolerated Dose (MTD)		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	Up to 30 days from the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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.	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	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	Baseline up to 28 days from the last dose of study drug
AUC(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	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.	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.	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.	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	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	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	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	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.	Baseline up to 30 days from the last dose of study drug

Collaborators and Investigators

• Sponsor: Jubilant Therapeutics Inc.
• Investigators: Study Director: Program Manager, Jubilant Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: February 11, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: SCLC; neuroendocrine; neuroendocrine prostate cancer; JBI-802
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: JBI-802-101

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