Back to resultsA Study of BTX-A51 in People With Advanced Solid Tumor or Non-Hodgkin Lymphoma
Primary Purpose
Advanced Solid Tumor, Non Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BTX-A51
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumor
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.
Sites / Locations
- Florida Cancer SpecialistsRecruiting
- The Linder Research Center at The Christ HospitalRecruiting
- Tennessee Oncology, PLLCRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
BTX-A51 Dose Cohort 1
BTX-A51 Dose Cohort 2
BTX-A51 Dose Cohort 3
BTX-A51 Dose Cohort 4
BTX-A51 Dose Cohort 5
BTX-A51 Dose Cohort 6
Arm Description
Starting dose (SD) of BTX-A51 administered orally 5 times per week in a 28-day cycle
Up to 2-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Up to 3.5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Up to 5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Up to 7-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Up to 10-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Outcomes
Primary Outcome Measures
Safety and tolerability of BTX-A51
To examine the incidence of clinical and laboratory adverse events after multiple doses of BTX-A51.
Defining the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of BTX-A51
To assess number of patients experiencing dose-limiting toxicities (DLTs)
Secondary Outcome Measures
Objective response rate (ORR)
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Duration of response (DoR)
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
Progression free survival (PFS)
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
Overall survival (OS)
To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause
Peak Plasma Concentration of BTX-A51
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of BTX-A51
Area under the plasma concentration of BTX-A51
To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of BTX-A51
Half-life of BTX-A51
To evaluate the half-life of BTX-A51 after single and repeated oral, once daily doses of BTX-A51
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04872166
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 7, 2021 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioTheryX, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Non Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
116 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BTX-A51 Dose Cohort 1
Arm Type
Experimental
Arm Description
Starting dose (SD) of BTX-A51 administered orally 5 times per week in a 28-day cycle
Arm Title
BTX-A51 Dose Cohort 2
Arm Type
Experimental
Arm Description
Up to 2-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Arm Title
BTX-A51 Dose Cohort 3
Arm Type
Experimental
Arm Description
Up to 3.5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Arm Title
BTX-A51 Dose Cohort 4
Arm Type
Experimental
Arm Description
Up to 5-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Arm Title
BTX-A51 Dose Cohort 5
Arm Type
Experimental
Arm Description
Up to 7-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Arm Title
BTX-A51 Dose Cohort 6
Arm Type
Experimental
Arm Description
Up to 10-times the SD of BTX-A51 administered orally 5 times per week in a 28-day cycle
Intervention Type
Drug
Intervention Name(s)
BTX-A51
Intervention Description
One 28 day cycle of treatment will consist of 4 weeks of treatment with a weekly dosing schedule of 5 days on/2 days off.
Primary Outcome Measure Information:
Title
Safety and tolerability of BTX-A51
Description
To examine the incidence of clinical and laboratory adverse events after multiple doses 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)
Title
Defining the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of BTX-A51
Description
To assess number of patients experiencing dose-limiting toxicities (DLTs)
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
Time Frame
Up to 2 years after the last treatment or upon death.
Title
Duration of response (DoR)
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
Time Frame
Up to 2 years after the last treatment or upon death.
Title
Progression free survival (PFS)
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
Time Frame
Up to 2 years after the last treatment or upon death.
Title
Overall survival (OS)
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
Time Frame
Up to 2 years after the last treatment or upon death.
Title
Peak Plasma Concentration of BTX-A51
Description
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses 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).
Title
Area under the plasma concentration of BTX-A51
Description
To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses 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).
Title
Half-life of BTX-A51
Description
To evaluate the half-life of BTX-A51 after single and repeated oral, once daily doses 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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tracy Lawhon, JD
Phone
858-699-2230
Email
tlawhon@biotheryx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Edgar Bautista, BS
Email
ebautista@biotheryx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tracy Lawhon, JD
Organizational Affiliation
BioTheryX, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Judy Wang, MD
Facility Name
The Linder Research Center at The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Starodub, MD
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Howard A Burris, III, MD
12. IPD Sharing Statement
Learn more about this trial
A Study of BTX-A51 in People With Advanced Solid Tumor or Non-Hodgkin Lymphoma
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