Clinical trial NCT05144334: A Study of BTX-1188 in Subjects With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Non Hodgkin Lymphoma
Acute Myeloid Leukemia
Lead sponsor: Biotheryx, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] with BTX-1188 in subjects with advanced malignancies
timeFrame: From first dose of BTX-1188 through 30 days after the last BTX-1188 treatment
measure: To determine the recommended Phase 2 dose (RP2D) of BTX-1188 in subjects with advanced malignancies
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Maximum Plasma Concentration of BTX-1188
timeFrame: 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).
measure: Peak Plasma Concentration of BTX-1188
timeFrame: 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).
measure: Area under the plasma concentration of BTX-1188
timeFrame: 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).
measure: Half-life of BTX-1188
timeFrame: 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).
measure: Objective response rate (ORR)
timeFrame: Up to 2 years after the last treatment or upon death.
measure: Best response
timeFrame: 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.
measure: Disease Control Rate (DCR)
timeFrame: 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.
measure: Duration of response (DoR)
timeFrame: Up to 2 years after the last treatment or upon death.
measure: Progression free survival (PFS)
timeFrame: Up to 2 years after the last treatment or upon death.
measure: Overall survival (OS)
timeFrame: Up to 2 years after the last treatment or upon death.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: Biotheryx, Inc.
name: Tracy Lawhon
role: STUDY_DIRECTOR
References: