Clinical trial NCT06515470: Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BTX-9341 in Advanced and/or Metastatic Breast Cancer
Official title: A First-in-Human, Open-Label, Dose Escalation and Expansion Trial of BTX-9341 in Participants With Advanced and/or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Keywords: HR+/HER2-
Lead sponsor: Biotheryx, Inc.
Sponsor class: INDUSTRY
First posted: 2024-07-23
Enrollment: 82
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: The purpose of this study is to test BTX-9341 alone or in combination with fulvestrant (a currently marketed medication for breast cancer) in participants with advanced and/or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. The study includes a dose escalation part (Part A) where small groups of participants will receive increasing doses of BTX-9341 or BTX-9341 + fulvestrant followed by a dose expansion part (Part B) where participants will receive the dose of BTX-9341 selected in Part A + fulvestrant.

Detailed description: This first-in-human (FIH), Phase 1 study of BTX-9341 is multicenter, nonrandomized, and open-label to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of BTX-9341 in participants with advanced and/or metastatic HR+/HER2 breast cancer. The study will include a dose escalation part (Part A) followed by a dose expansion part (Part B). During Part A, BTX-9341 will initially be dose escalated alone and then in combination with fulvestrant. A single combination therapy cohort of BTX-9341 + fulvestrant will be further explored in Part B. BTX-9341 will be administered orally in 28-day treatment cycles.

Eligibility criteria: Inclusion Criteria:

* Metastatic and/or locally advanced HR+/HER2- breast cancer (dose escalation: measurable disease and/or at least 1 lytic or mixed \[lytic + sclerotic\] bone lesion that can be assessed by CT or MRI or non-measurable disease \[including bone lesions\]; dose expansion: measurable disease)
* Dose escalation: (a) received not more than 1 chemotherapy in the metastatic/advanced setting; (b) no limit to the lines of endocrine therapy (monotherapy or combination therapy) in the metastatic setting; (c) received CDK4/6 inhibitor therapy
* Dose expansion: (a) received not more than 1 chemotherapy in metastatic/advanced setting; (b) received not more than 2 lines of endocrine therapy (monotherapy or combination therapy) and must have been on prior endocrine therapy for at least 6 months before progression; (c) received at most 2 lines of CDK4/6 inhibitor therapy (1 in the adjuvant setting and 1 in the metastatic setting) and must have been on prior CDK4/6 inhibitor therapy for at least 6 months
* Acceptable hematologic function

  1. ANC ≥ 1500 per mL. Note: Use of growth-factors to maintain the ANC criterion is prohibited.
  2. Platelet count ≥ 100,000 per mL. Note: Use of transfusions or thrombopoietic agents to achieve the baseline platelet count criterion is prohibited.
  3. Hemoglobin ≥ 9.0 g/dL. Note: Packed red blood cell transfusion is allowed up to 14 days prior to trial entry.
* Acceptable liver function

  1. Bilirubin ≤ 2.0 × institutional upper limit of normal (ULN) (or \< 3.0 × institutional ULN if Gilbert's disease is present)
  2. Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × institutional ULN (≤ 5.0 × institutional ULN if liver metastases present)
  3. Alkaline phosphatase ≤ 2.5 × institutional ULN (≤ 5.0 × institutional ULN if bone or liver metastases present)
* Able and willing to sign informed consent
* Meets all study requirements in the opinion of the Investigator

Exclusion Criteria:

* RB1 (retinoblastoma) gene mutation
* Symptomatic visceral disease
* Clinical evidence or history of central nervous system metastasis
* Abnormalities in coagulation, such as bleeding diathesis, or treatment with anticoagulants precluding injections of fulvestrant or luteinizing hormone-releasing hormone (LHRH) agonist

Primary outcomes:
measure: Safety and Tolerability of BTX-9341
timeFrame: Up to 28 days after last dose of BTX-9341
measure: Part A: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: 28 days
measure: Part A: Determine MTD/MED of BTX-9341 in monotherapy
timeFrame: Approximately 1 year from study start
measure: Part A: Determine MTD/MED of BTX-9341 in combination therapy
timeFrame: Approximately 18 months from study start
measure: Part B Combination Therapy: Objective Response (OR) rate
timeFrame: Approximately 18 months from start of Part B
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Biotheryx Investigative Site
state: Minnesota
city: Omaha
country: United States
facility: Biotheryx Investigative Site
state: Nebraska
city: Houston
country: United States
facility: Biotheryx Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Biotheryx Investigative Site
state: Texas
city: West Valley City
country: United States
facility: Biotheryx Investigative Site
state: Utah
city: Fairfax
country: United States
facility: Biotheryx Investigative Site
state: Virginia
Study officials:
affiliation: Chief Medical Officer
name: Jeremy Barton, MD
role: STUDY_DIRECTOR
References: