Breast Cancer
Conditions
Keywords
HR+/HER2-
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.
Interventions
DRUGBTX-9341
Daily oral dose in 28-day cycles until maximum tolerated dose (MTD) or maximum evaluable dose (MED) determined
DRUGFulvestrant
500 mg intramuscular injections on Day 15 and then every 28 days
Sponsors
Biotheryx, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of BTX-9341 | Up to 28 days after last dose of BTX-9341 | Frequency and severity, incidence of treatment-emergent and treatment-related adverse events using NCI-CTCAE v5.0 |
| Part A: Number of Participants With Dose Limiting Toxicities (DLTs) | 28 days | DLT rate in Cycle 1 |
| Part A: Determine MTD/MED of BTX-9341 in monotherapy | Approximately 1 year from study start | Based on CTCAE v5.0 assessment of adverse events |
| Part A: Determine MTD/MED of BTX-9341 in combination therapy | Approximately 18 months from study start | Based on CTCAE v5.0 assessment of adverse events |
| Part B Combination Therapy: Objective Response (OR) rate | Approximately 18 months from start of Part B | OR is the confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 as determined by Investigator assessment |
Countries
United States
Contacts
Primary ContactDanette Powell
Outcome results
None listed