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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.

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.

Condition or disease Intervention/treatment Phase
Locally Advanced Solid Tumor Metastatic Solid Tumor Drug: JBI-802 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A First-in-Human, Open-label, Dose Escalation and Expansion Study of Orally Administered JBI-802 in Patients With Advanced Solid Tumors
Actual Study Start Date : April 8, 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : August 2025

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




Primary Outcome Measures :
  1. Maximum-Tolerated Dose (MTD) [ Time Frame: 28-day cycle ]
  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05268666


Contacts
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Contact: Chief Scientific Officer (443) 515-9637 luca.rastelli@jubilanttx.com
Contact: Director, Program Management rajeev.mohan@jubilanttx.com

Locations
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United States, Colorado
Sarah Cannon Research Institute at HealthOne Recruiting
Denver, Colorado, United States, 82018
United States, Ohio
The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Virginia
NEXT Virginia, LLC Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Jubilant Therapeutics Inc.
Investigators
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Study Director: Program Manager Jubilant Therapeutics Inc.
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Responsible Party: Jubilant Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT05268666    
Other Study ID Numbers: JBI-802-101
First Posted: March 7, 2022    Key Record Dates
Last Update Posted: August 22, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jubilant Therapeutics Inc.:
SCLC
neuroendocrine prostate cancer
neuroendocrine
JBI-802
Additional relevant MeSH terms:
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Neoplasms