Clinical Trials /

A Study of BTX-A51 in People With Advanced Solid Tumor or Non-Hodgkin Lymphoma

NCT04872166

Description:

This is a multicenter, open label, nonrandomized, sequential dose escalation/cohort expansion, multiple dose study designed to evaluate the safety, toxicity, and PK as well as preliminary efficacy of BTX-A51 in subjects with advanced solid tumors and NHL. The study will be done in two phases, described below. Phase 1a (Dose Escalation Phase): The Phase 1a portion is designed to determine the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of orally administered BTX-A51. BTX-A51 will be administered once daily on a weekly schedule of 5 days on/2 days off. Dose escalation will proceed according to a modified 3+3 design. Each cycle will consist of 28 days (4 weeks), and the DLT observation period will be the first cycle (i.e., 28 days after initiation of dosing). A DLT may be observed in no more than 0 out of 3 or 1 out of 6 subjects who have completed the DLT observation period before the next cohort initiates accrual. Barring DLT, sequential dose escalation of BTX-A51 is planned with up to a total of 6 dose levels; on the basis of these an MTD will be identified. The MTD is defined as the highest dose level with a subject incidence of DLTs of 0 or 1 out of 6 during the first 28 days of study drug dosing. A minimum of 6 subjects needs to be treated at a dose level before this dose level can be deemed as the MTD. Phase 1b (Cohort Expansion Phase): Dose expansion may begin when the RP2D has been determined. Up to 40 additional subjects will be enrolled to evaluate safety and preliminary efficacy of BTX-A51 in subjects with documented MYC genomic amplified/overexpressed tumors. Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of BTX-A51 in People With Advanced Solid Tumor or Non-Hodgkin Lymphoma
  • Official Title: An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, and Pharmacokinetics of BTX A51 in Subjects With Advanced Solid Tumors and Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: BTX-A51-002
  • NCT ID: NCT04872166

Conditions

  • Advanced Solid Tumor
  • Non Hodgkin Lymphoma

Interventions

DrugSynonymsArms
BTX-A51BTX-A51 Dose Cohort 1

Purpose

This is a multicenter, open label, nonrandomized, sequential dose escalation/cohort expansion, multiple dose study designed to evaluate the safety, toxicity, and PK as well as preliminary efficacy of BTX-A51 in subjects with advanced solid tumors and NHL. The study will be done in two phases, described below. Phase 1a (Dose Escalation Phase): The Phase 1a portion is designed to determine the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of orally administered BTX-A51. BTX-A51 will be administered once daily on a weekly schedule of 5 days on/2 days off. Dose escalation will proceed according to a modified 3+3 design. Each cycle will consist of 28 days (4 weeks), and the DLT observation period will be the first cycle (i.e., 28 days after initiation of dosing). A DLT may be observed in no more than 0 out of 3 or 1 out of 6 subjects who have completed the DLT observation period before the next cohort initiates accrual. Barring DLT, sequential dose escalation of BTX-A51 is planned with up to a total of 6 dose levels; on the basis of these an MTD will be identified. The MTD is defined as the highest dose level with a subject incidence of DLTs of 0 or 1 out of 6 during the first 28 days of study drug dosing. A minimum of 6 subjects needs to be treated at a dose level before this dose level can be deemed as the MTD. Phase 1b (Cohort Expansion Phase): Dose expansion may begin when the RP2D has been determined. Up to 40 additional subjects will be enrolled to evaluate safety and preliminary efficacy of BTX-A51 in subjects with documented MYC genomic amplified/overexpressed tumors. Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days).

Trial Arms

NameTypeDescriptionInterventions
BTX-A51 Dose Cohort 1ExperimentalStarting dose (SD) of BTX-A51 administered orally 5 times per week in a 28-day cycle
  • BTX-A51
BTX-A51 Dose Cohort 2ExperimentalUp to 2-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
  • BTX-A51
BTX-A51 Dose Cohort 3ExperimentalUp to 3.5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
  • BTX-A51
BTX-A51 Dose Cohort 4ExperimentalUp to 5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
  • BTX-A51
BTX-A51 Dose Cohort 5ExperimentalUp to 7-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
  • BTX-A51
BTX-A51 Dose Cohort 6ExperimentalUp to 10-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
  • BTX-A51

Eligibility Criteria

        Inclusion Criteria:

          -  Demonstration of understanding and voluntarily signing of an informed consent form

          -  Age ≥ 18 years

          -  Histologically or cytologically documented, incurable or metastatic solid tumor or B
             cell NHL that is refractory to or intolerant of all standard therapy or for which no
             standard therapy is available

          -  Expansion Phase only: Documentation of MYC genomic amplification/overexpression by
             tumor or blood-based analysis.

          -  Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
             (RECIST v1.1). NHL subjects must have bi-dimensionally measurable disease on cross
             sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) as
             defined by Lugano criteria (Cheson, Fisher, et al., 2014).

          -  Adequate organ function

          -  Females of childbearing age must not be pregnant at time of Screening/beginning of
             treatment and agree to either abstain from sexual intercourse or use highly effective
             methods of contraception (for up to 3 months after last dose of study drug)

          -  Males sexually active with a woman of childbearing age must agree to use barrier
             method of birth control during and after the study (up to 3 months after last dose of
             study drug)

        Exclusion Criteria:

          -  Life expectancy <3 months, as determined by the Investigator.

          -  Treatment with any local or systemic antineoplastic therapy (including chemotherapy,
             hormonal therapy, or radiation) within 3 weeks prior to first dose of BTX-A51

          -  Chronic use of corticosteroids in excess of 10 mg daily of prednisone or equivalent
             within 4 weeks prior to first dose of BTX-A51

          -  Major trauma or major surgery within 4 weeks prior to first dose of BTX-A51.

          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤1
             except for alopecia or Grade ≤2 immunotherapy-related thyroid toxicity.

          -  History of, or known, central nervous system (CNS) disease involvement, or prior
             history of NCI CTCAE Grade ≥3 drug-related CNS toxicity.

          -  Clinically significant cardiac disease

          -  Active uncontrolled systemic fungal, bacterial, mycobacterial, or viral infection

          -  Known positive test result for human immunodeficiency virus (HIV) or acquired immune
             deficiency syndrome (AIDS)

          -  Active hepatitis C virus (HCV) or hepatitis B virus (HBV)

          -  Second primary malignancy that has not been in remission for greater than 3 years

          -  Any serious underlying medical (e.g., pulmonary, renal, hepatic, gastrointestinal, or
             neurological) or psychiatric condition (e.g., alcohol or drug abuse, dementia or
             altered mental status) or any issue that would limit compliance with study
             requirements

          -  Pregnant, lactating, or breastfeeding.

          -  Participation or plans to participate in another interventional clinical study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of BTX-A51
Time Frame:From first dose of BTX-A51 through 30 days after the last BTX-A51 treatment (subjects will will be offered continued access to study BTX-A51 until disease progression or unacceptable toxicity)
Safety Issue:
Description:To examine the incidence of clinical and laboratory adverse events after multiple doses of BTX-A51.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 2 years after the last treatment or upon death.
Safety Issue:
Description:To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Measure:Duration of response (DoR)
Time Frame:Up to 2 years after the last treatment or upon death.
Safety Issue:
Description:To evaluate the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause
Measure:Progression free survival (PFS)
Time Frame:Up to 2 years after the last treatment or upon death.
Safety Issue:
Description:To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause
Measure:Overall survival (OS)
Time Frame:Up to 2 years after the last treatment or upon death.
Safety Issue:
Description:To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause
Measure:Peak Plasma Concentration of BTX-A51
Time Frame:PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, 8, and 24 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Safety Issue:
Description:To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of BTX-A51
Measure:Area under the plasma concentration of BTX-A51
Time Frame:PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, 8, and 24 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Safety Issue:
Description:To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of BTX-A51
Measure:Half-life of BTX-A51
Time Frame:PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, 8, and 24 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Safety Issue:
Description:To evaluate the half-life of BTX-A51 after single and repeated oral, once daily doses of BTX-A51

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BioTheryX, Inc.

Last Updated

June 9, 2021