BTX-A51 in Patients With Liposarcoma

A Pilot Study of BTX-A51 in Patients With Metastatic and/or Recurrent Liposarcomas Characterized by MDM2 Amplifications

This study is testing if the recommended dose of BTX-A51 is safe and tolerable in participants with liposarcoma.

The name of the study drug used in this research study is:

-BTX-A51 (a type of kinase inhibitor)

Study Overview

• Status: Not yet recruiting
• Conditions: Liposarcoma; MDM2 Gene Amplification; Metastatic Liposarcoma; Unresectable Liposarcoma; Recurrent Liposarcoma
• Intervention / Treatment: Drug: BTX-A51

Detailed Description

This is a single arm, pilot study assessing the safety and preliminary exploration of BTX-A51 in participants with metastatic and/or recurrent liposarcomas characterized by Murine Double Minute Clone 2 (MDM2) amplifications. BTX-A51 works in a different way from currently approved therapies used to treat liposarcoma by blocking proteins called CK1α and CDK9.

The U.S. Food and Drug Administration (FDA) has not approved BTX-A51 as a treatment for Liposarcoma.

The research study procedures include screening for eligibility, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission Tomography (PET) scans, blood tests, and tumor biopsies.

Participants will receive study treatment for as long as there are no serious side effects, and disease does not get worse. Participants will be followed for 1 year after the last dose of BTX-A51.

It is expected that about 12 people will take part in this research study.

Edgewood Oncology is supporting this research study by providing the study drug.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael Wagner, MD; Phone Number: 617-632-5204; Email: MICHAEL_WAGNER@DFCI.HARVARD.EDU
• Study Contact Backup: Name: Michael Wagner, MD; Phone Number: 617-632-3352; Email: michael_wagner@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
      • Principal Investigator: Michael Wagner, MD
      • Contact: Michael Wagner, MD; Phone Number: 617-632-3352; Email: michael_wagner@dfci.harvard.edu
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
      • Principal Investigator: Michael Wagner, MD
      • Contact: Michael Wagner, MD; Phone Number: 617-632-3352; Email: michael_wagner@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Study participants must have histologically-confirmed metastatic and/or recurrent liposarcoma (limited to the subtypes of well-differentiated and/or dedifferentiated liposarcoma, which are associated with MDM2 amplifications).
• ECOG performance status ≤2

• Adequate organ and marrow function as defined by the following metrics resulted within 7 days of study enrollment:

  • WBC >3000/mm3
  • Platelets >75,000μl
  • ANC >1500μl
  • Hgb >9g/dl
  • Creatinine <1.5 x ULN or measured CrCl of >60ml/m2/1.73 m2
  • Total bilirubin <2 x ULN
  • AST/ALT <3 x ULN

• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as

  ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.

• Patients must have recovered from toxicity related to prior therapy to grade <=1 (defined by CTCAE v5.0) (except alopecia and neuropathy, or immunotherapy related hypothyroidism)
• As the effect of this study drug on the developing human fetus is not known, women of child-bearing potential and men must agree to use at least 2 methods of contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion.
• Female patient of childbearing potential has a negative serum pregnancy test within 7 days of study enrollment.
• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥18 years
• Patients must have completed all prior anti-cancer treatment for liposarcoma, including radiation, ≥ 14 days prior to registration.

Exclusion Criteria:

• Patient with current evidence of active and uncontrolled infection, NYHA Class III-IV CHF, documented Child's class B-C cirrhosis, or uncontrolled medical disease which in the opinion of the investigator or the sponsor could compromise safety and/or assessment of efficacy.
• Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR result before enrollment; those who are PCR positive will be excluded.
• Major surgical procedure or open surgical biopsy within 28 days of first dose of study drug
• Active central nervous system (CNS) disease involvement, or prior history of NCI CTCAE Grade ≥3 drug-related CNS toxicity. Subject with known CNS metastases that are treated and stable (without evidence of CNS toxicity) and are not requiring systemic steroids are allowed to be enrolled.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Myocardial infarction within 12 months of screening
• Use of any other concurrent investigational agents or anticancer agents, excluding hormonal therapy for breast or prostate cancer
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BTX- A51, breastfeeding should be discontinued if the mother is treated with BTX-A51.
• Inability to swallow pills or inadequate GI absorption in the opinion of the treating investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BTX-A51; Participants will be enrolled and will complete study procedures as follows: Baseline visit with tumor biopsy.; Tumor biopsy at the end of Cycle 1.; Radiologic imaging every 2 cycles.; Cycle 1 through End of Treatment:--Day 1 of 28 day cycle: Predetermined dose of BTX-A51 3x weekly.; End of Treatment visit with radiologic imaging.; Follow-up: every 3 months for 1 year.	Drug: BTX-A51; Multi-kinase inhibitor, 1.0 mg, 2.0 mg, and 7.0 mg immediate-release capsules, taken orally per protocol.; Other Names: C32H41ClN6O6S2; (1r,4r)-N 1-(5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-l H pyrazol-3-yl)pyrimidin-2-yl)cyclohexane-l ,4-diamine bis(4-methylbenzenesulfonate),

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events, with laboratory abnormalities, with dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event	Safety and tolerability will be monitored through continuous reporting of treatment-emergent and treatment-related adverse events, laboratory abnormalities, and incidence of subjects experiencing dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event. Toxicities are to be assessed according to the CTCAEv5.	All AEs will be recorded from the time the subject signs informed consent until 30 days after the last dose of study BTX-A51.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year Progression-Free Survival (PFS) Rate	1-year PFS is a probability estimated using progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.	1 year
1-year Overall Survival (OS)	1-year OS is a probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at date last known alive.	1 year
Overall Response Rate (ORR)	The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.	ORR expected to be observed up to 3 years

Collaborators and Investigators

• Sponsor: Michael Wagner
• Collaborators: Edgewood Oncology Inc.
• Investigators: Principal Investigator: Michael Wagner, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Liposarcoma; Unresectable Liposarcoma; Metastatic Liposarcoma; Recurrent Liposarcoma; MDM2 Gene Amplification
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Sarcoma; Neoplasms, Adipose Tissue; Recurrence; Liposarcoma
• Other Study ID Numbers: 24-156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No