A Study of BTX-1188 in Subjects With Advanced Malignancies

NCT05144334 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BTX-1188-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

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.

Conditions

Advanced Solid Tumor; Non Hodgkin Lymphoma; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• Maximum Plasma Concentration 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).

• Peak Plasma Concentration 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).

• Area under the plasma concentration 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).

• Half-life 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).

• Objective response rate (ORR)

  Up to 2 years after the last treatment or upon death.

Study Arms (7)

BTX-1188 Dose Cohort 1

EXPERIMENTAL

Starting dose of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

BTX-1188 Dose Cohort 2

EXPERIMENTAL

First dose escalation of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

BTX-1188 Dose Cohort 3

EXPERIMENTAL

Second dose escalation of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

BTX-1188 Dose Cohort 4

EXPERIMENTAL

Third dose escalation of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

BTX-1188 Dose Cohort 5

EXPERIMENTAL

Fourth dose escalation of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

BTX-1188 Dose Cohort 6

EXPERIMENTAL

Fifth dose escalation of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

BTX-1188 Dose Cohort 7

EXPERIMENTAL

Sixth dose escalation of BTX-1188 administered orally per dosing schedule

Drug: BTX-1188

Interventions

BTX-1188 DRUG

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

BTX-1188 Dose Cohort 1; BTX-1188 Dose Cohort 2; BTX-1188 Dose Cohort 3; BTX-1188 Dose Cohort 4; BTX-1188 Dose Cohort 5; BTX-1188 Dose Cohort 6; BTX-1188 Dose Cohort 7

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biotheryx, Inc.: lead

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases

Study Officials

• Tracy Lawhon

  Biotheryx, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: December 3, 2021
• Study Start: January 24, 2022
• Primary Completion: September 12, 2023
• Study Completion: September 12, 2023
• Last Updated: September 18, 2023

Record last verified: 2023-09

Locations

US (4)