A Study of BTX-1188 in Subjects With Advanced Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title:

An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, Pharmacokinetics, and Preliminary Activity of BTX-1188 in Subjects With Advanced Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05144334
• Other study ID #: BTX-1188-001
• Status: Terminated
• Phase: Phase 1
• Start date: January 24, 2022
• Est. completion date: September 12, 2023

Study information

• Verified date: September 2023
• Source: BioTheryX, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open label, nonrandomized, sequential dose escalation, multiple dose study designed to evaluate the safety, toxicity, and pharmacokinetics (PK) as well as preliminary efficacy of BTX-1188 orally administered in subjects with advanced malignancies.

Description:

Study BTX-1188-001 is a multicenter, open label, nonrandomized, sequential dose escalation study to evaluate the safety, toxicity, PK, and preliminary efficacy of BTX-1188. Dose escalation will be conducted in subjects with acute myeloid leukemia (AML) and advanced lymphoid and solid tumors. Based on the results of the dose escalation, a recommended Phase 2 dose will be determined.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: September 12, 2023
• Est. primary completion date: September 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

• Age = 18 years

• Part A - Relapsed or refractory AML, according to the World Health Organization (WHO) classification (Arber, Orazi, et al., 2016). Subjects must be ineligible for or have exhausted standard therapeutic options that would otherwise be likely to provide clinical benefit. Part B - B cell NHL that is refractory to or intolerant of all standard therapy or for which no standard therapy is available or histologically or cytologically documented, incurable or metastatic solid tumor that has failed all available standard therapies with known benefit.

• Subjects with solid tumors must have 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 must avoid pregnancy for at least 4 weeks before beginning BTX-1188 therapy, during therapy, during dose interruptions, and for at least 4 weeks after completing therapy and agree to either abstain from sexual intercourse or use two highly effective methods of contraception (for up to 4 weeks 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 and not donate sperm (for up to 4 weeks 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-1188

• Immediate life-threatening severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation

• Major trauma or major surgery within 4 weeks prior to first dose of BTX-1188.

• 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Advanced Solid Tumor
• Non Hodgkin Lymphoma

Intervention

Drug:
• BTX-1188
One 28 day cycle of treatment will consist of 4 weeks of treatment with BTX-1188 administered orally per dosing schedule.

Locations

Country	Name	City	State
United States	The Christ Hospital	Cincinnati	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
BioTheryX, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] with BTX-1188 in subjects with advanced malignancies	To examine the incidence of clinical and laboratory adverse events after multiple doses of BTX-1188	From first dose of BTX-1188 through 30 days after the last BTX-1188 treatment
Primary	To determine the recommended Phase 2 dose (RP2D) of BTX-1188 in subjects with advanced malignancies	To assess number of patients experiencing dose-limiting toxicities (DLTs)	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Maximum Plasma Concentration of BTX-1188	To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of BTX-1188	PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Secondary	Peak Plasma Concentration of BTX-1188	To evaluate the observed time of peak concentration (Tmax) after single and repeated oral, once daily doses of BTX-1188	PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Secondary	Area under the plasma concentration of BTX-1188	To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of BTX-1188.	PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Secondary	Half-life of BTX-1188	To evaluate the half-life of BTX-1188 after single and repeated oral, once daily doses of BTX-1188.	PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Secondary	Objective response rate (ORR)	To evaluate the objective response rate (ORR) as determined by the specific disease response criteria.	Up to 2 years after the last treatment or upon death.
Secondary	Best response	To evaluate the complete remission/response [CR], CR with incomplete blood count recovery [CRi], morphologic leukemia free state [MLFS], partial remission/response [PR], stable disease or progression as determined by the specific disease response criteria.	For subjects with AML, response will be evaluated at the end of each cycle (each cycle is 28 days) and after the last dose of BTX-1188 (approximately 36 months). For subjects with NHL or solid tumors, response will be evaluated every 8-weeks.
Secondary	Disease Control Rate (DCR)	To evaluate the DCR (response + stable disease) as determined by the specific disease response criteria.	For subjects with AML, response will be evaluated at the end of each cycle (each cycle is 28 days) and after the last dose of BTX-1188 (approximate 36 months). For subjects with NHL or solid tumors, response will be evaluated every 8-weeks.
Secondary	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.	Up to 2 years after the last treatment or upon death.
Secondary	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.	Up to 2 years after the last treatment or upon death.
Secondary	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.	Up to 2 years after the last treatment or upon death.