A Study of BTX-A51 in People With Advanced Solid Tumor and Breast Cancer

Description

This is a multicenter, open label, nonrandomized, sequential dose escalation/dose ranging, multiple dose study designed to evaluate the safety, toxicity, and PK as well as preliminary efficacy of BTX-A51 alone and in combination with fulvestrant in subjects with advanced solid tumors. The study will be done in three 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 (Monotherapy Dose Ranging Phase): Dose expansion may begin when the RP2D has been determined. Up to 40 additional subjects at each of the 2 dose levels will be enrolled to evaluate safety and preliminary efficacy of BTX-A51 in subjects with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-), GATA3 mutant (mt) and wild-type (wt) metastatic breast cancer (mBC). Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days). Phase 1c (Combination Safety Phase): The Phase 1c portion will evaluate the safety and tolerability of orally administered BTX-A51 at two dose levels combined with fulvestrant. The first combo cohort may be initiated after DEC review of the 6 subject lead-in phase of the high dose monotherapy cohort in Phase 1b. Dose escalation will proceed according to a 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).

Conditions

Advanced Solid Tumor, Metastatic Breast Cancer

Study Overview

Study Details

Study overview

This is a multicenter, open label, nonrandomized, sequential dose escalation/dose ranging, multiple dose study designed to evaluate the safety, toxicity, and PK as well as preliminary efficacy of BTX-A51 alone and in combination with fulvestrant in subjects with advanced solid tumors. The study will be done in three 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 (Monotherapy Dose Ranging Phase): Dose expansion may begin when the RP2D has been determined. Up to 40 additional subjects at each of the 2 dose levels will be enrolled to evaluate safety and preliminary efficacy of BTX-A51 in subjects with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-), GATA3 mutant (mt) and wild-type (wt) metastatic breast cancer (mBC). Dosing in this phase of the study consists of the first cycle of therapy (i.e., 28 days). Phase 1c (Combination Safety Phase): The Phase 1c portion will evaluate the safety and tolerability of orally administered BTX-A51 at two dose levels combined with fulvestrant. The first combo cohort may be initiated after DEC review of the 6 subject lead-in phase of the high dose monotherapy cohort in Phase 1b. Dose escalation will proceed according to a 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).

An Open Label, Escalating Multiple Dose Study to Evaluate the Safety, Toxicity, and Pharmacokinetics of BTX A51 Alone and in Combination With Fulvestrant in Subjects With Advanced Solid Tumors and Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Metastatic Breast Cancer

A Study of BTX-A51 in People With Advanced Solid Tumor and Breast Cancer

Condition
Advanced Solid Tumor
Intervention / Treatment

-

Contacts and Locations

Lake Mary

Florida Cancer Specialists, Lake Mary, Florida, United States, 32746

Sarasota

Florida Cancer Specialists, Sarasota, Florida, United States, 34232

Cincinnati

The Linder Research Center at The Christ Hospital, Cincinnati, Ohio, United States, 45219

Nashville

SCRI Oncology Partners, Nashville, Tennessee, United States, 37203

Nashville

Tennessee Oncology, PLLC, Nashville, Tennessee, United States, 37203

Houston

The University of Texas MD Anderson Cancer Center, Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Demonstration of understanding and voluntarily signing of an informed consent form
  • * Age ≥ 18 years
  • * Histologically or cytologically documented, incurable or metastatic solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available
  • * Phase 1b and 1c only: Histologically confirmed diagnosis of ER+, HER2- mBC not amenable to resection or radiation therapy with curative intent.
  • * Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
  • * 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)
  • * 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.

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Edgewood Oncology Inc.,

Zung Thai, MD, STUDY_DIRECTOR, Edgewood Oncology Inc.

Study Record Dates

2027-05