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

Metastatic Breast Cancer Clinical Trial

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 Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04872166
• Other study ID #: BTX-A51-002
• Status: Recruiting
• Phase: Phase 1
• Start date: June 7, 2021
• Est. completion date: May 2027

Study information

• Verified date: February 2024
• Source: Edgewood Oncology Inc.
• Contact: Zung Thai, MD
• Phone: 415-225-9338
• Email: zung[@]edgewoodonc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 breast cancer. 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 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: May 2027
• Est. primary completion date: May 2026
• 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

• 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

• Expansion Phase 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)

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• BTX-A51
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.

Locations

Country	Name	City	State
United States	The Linder Research Center at The Christ Hospital	Cincinnati	Ohio
United States	Florida Cancer Specialists	Lake Mary	Florida
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Edgewood Oncology Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of BTX-A51	To examine the incidence of clinical and laboratory adverse events after multiple doses of BTX-A51.	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)
Primary	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)	At the end 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	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.
Secondary	Peak Plasma Concentration of BTX-A51	To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of BTX-A51	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).
Secondary	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	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).
Secondary	Half-life of BTX-A51	To evaluate the half-life of BTX-A51 after single and repeated oral, once daily doses of BTX-A51	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).