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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05268666
Recruitment Status : Recruiting
First Posted : March 7, 2022
Last Update Posted : August 22, 2022
Sponsor:
Information provided by (Responsible Party):
Jubilant Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE February 11, 2022
First Posted Date  ICMJE March 7, 2022
Last Update Posted Date August 22, 2022
Actual Study Start Date  ICMJE April 8, 2022
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2022)
  • Maximum-Tolerated Dose (MTD) [ Time Frame: 28-day cycle ]
  • Investigator-Assessed ORR (Part 2) [ Time Frame: Up to 30 days from the last dose of study drug ]
    Defined as either complete response (CR) or partial response (PR) as defined by RECIST version 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2022)
  • Incidence of AEs [ Time Frame: Up to 30 days from the last dose of study drug ]
    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
  • Cmax: Maximum Plasma Concentration JBI-802 [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    Defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations.
  • Tmax: Time of Maximum Plasma Concentration JBI-802 [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    Defined as the time at which the Cmax occurs.
  • Clast: 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 ]
    Last Observed (quantifiable) Plasma Concentration in units of ng/mL JBI-802
  • AUC(0-last): Area Under the Concentration-time Curve from Dosing (time 0) to Time of Last Measured Concentration JBI-802 [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    AUCs will be reported in units of h×ng/mL
  • AUC(0-t) (partial AUC): Area Under the Concentration-time Curve from Dosing (time 0) to Time t JBI-802 [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    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
  • Vd/F: Apparent Volume of Distribution During Terminal Phase (Vz/F) After Oral Administration calculated as (CL/F)/ Ke [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    Volume will be reported in units of L.
  • CL/F: Apparent Oral Clearance (CL/F) computed as Dose/AUC [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    Clearance will be reported in units of L/h.
  • t½: The Apparent Terminal Elimination Half-life JBI-802 [ Time Frame: Baseline up to 28 days from the last dose of study drug ]
    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.
  • Investigator-Assessed Overall Response Rate (ORR) (Part 1) [ Time Frame: Up to 30 days from the last dose of study drug ]
    ORR is defined as the percentage of patients with a confirmed complete response (CR) or a partial response based on RECIST 1.1
  • Duration of Response (DOR) [ Time Frame: Up to 30 days from the last dose of study drug ]
    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
  • PFS: Progression Free Survival [ Time Frame: Date patient started study drug to date of progression, assessed up to 30 months ]
    The time from the date the patient started study drug to the date the patient experiences an event of disease progression
  • OS: Overall Survival [ Time Frame: Date patient started study drug to date of death for any cause, assessed up to 30 months ]
    The time from the date patient started study drug to death for any reason
  • PSA 50 Response Rate in Patients with Prostate Cancer [ Time Frame: Baseline up to 30 days from the last dose of study drug ]
    The percentage of patients who experience a ≥50% decline in PSA from baseline.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Orally Administered JBI-802, an LSD1/HDAC6 Inhibitor, in Patients With Advanced Solid Tumors
Official Title  ICMJE A First-in-Human, Open-label, Dose Escalation and Expansion Study of Orally Administered JBI-802 in Patients With Advanced Solid Tumors
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Locally Advanced Solid Tumor
  • Metastatic Solid Tumor
Intervention  ICMJE Drug: JBI-802
LSD1/HDAC6 inhibitor
Study Arms  ICMJE Experimental: JBI-802
10 mg JBI-802 once daily as the starting dose with 4 days on/3 days off cycle
Intervention: Drug: JBI-802
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 24, 2022)
126
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2025
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chief Scientific Officer (443) 515-9637 luca.rastelli@jubilanttx.com
Contact: Director, Program Management rajeev.mohan@jubilanttx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05268666
Other Study ID Numbers  ICMJE JBI-802-101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Jubilant Therapeutics Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Jubilant Therapeutics Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Program Manager Jubilant Therapeutics Inc.
PRS Account Jubilant Therapeutics Inc.
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP