Trial of BDC-1001 +/- Pertuzumab in Subjects with HER2-Positive Metastatic Breast Cancer
- Conditions
- Metastatic Breast CancerHER2-positive Breast Cancer
- Interventions
- Registration Number
- NCT05954143
- Lead Sponsor
- Bolt Biotherapeutics, Inc.
- Brief Summary
This is an open-label, Phase 2 study to evaluate preliminary anti-tumor activity, safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of BDC-1001 administered as a single agent and in combination with pertuzumab in subjects with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) previously treated with trastuzumab deruxtecan (Enhertu®).
- Detailed Description
Eligible subjects will be randomly assigned in a 1:1 ratio to receive BDC-1001 as a single agent or BDC-1001 in combination with pertuzumab. Within each treatment arm, a Simon 2-stage design will be applied. Subjects will receive study treatment (i.e., BDC-1001 or BDC-1001 in combination with pertuzumab) for up to 24 months after Cycle 1 Day 1 (C1D1), until disease progression, unacceptable toxicity, or withdrawal for any reason.
Bolt amended the protocol to transition any subjects still receiving BDC-1001 to continue receiving BDC-1001 in the Maintenance Phase. Subjects remaining on BDC-1001 will continue to receive BDC-1001 until a criterion for discontinuation has been met.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
- Histologically confirmed adenocarcinoma of the breast that is HER2+ (IHC 3+ or gene amplification by ISH or NGS).
- Have received 2 or more prior lines of anti-HER2-directed therapies, at least 1 in the metastatic setting and including trastuzumab deruxtecan.
- Measurable disease as determined by RECIST v.1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Have life expectancy of greater than 12 weeks per the Investigator.
- All subjects must agree to have a biopsy prior to enrollment. If, in the judgment of the Investigator, a biopsy is not safely accessible or clinically feasible an archival tumor tissue sample must be submitted in lieu of a freshly collected specimen.
Key
- History of severe hypersensitivity to any ingredient of BDC-1001 or pertuzumab.
- Previous treatment with a small molecule TLR7/8 agonist or TLR7/8 agonist that has been conjugated to tumor-targeting antibody such as ISACs within 12 months before starting study treatment.
- Impaired cardiac function or history of clinically significant cardiac disease.
- Human Immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
- Central nervous system metastases with the exception of disease that is asymptomatic, clinically stable, and has not required steroids for at least 28 days before starting study treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BDC-1001 in Combination With Pertuzumab BDC-1001 BDC-1001 administered intravenously (IV) every 2 weeks, in combination with pertuzumab administered intravenously (IV) as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose every 3 weeks. BDC-1001 Single Agent BDC-1001 BDC-1001 administered intravenously (IV) every 2 weeks BDC-1001 in Combination With Pertuzumab Pertuzumab BDC-1001 administered intravenously (IV) every 2 weeks, in combination with pertuzumab administered intravenously (IV) as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose every 3 weeks.
- Primary Outcome Measures
Name Time Method Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab 12 weeks Objective Response Rate (ORR) according to RECIST v1.1
- Secondary Outcome Measures
Name Time Method Incidence of treatment-emergent events with BDC-1001 as a single agent and in combination with pertuzumab Up to 24 months Treatment-emergent Serious Adverse Events (TESAEs)
Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab Up to 24 months Overall Survival (OS)
Immunogenicity of BDC-1001 as a single agent and in combination with pertuzumab Up to 24 months Incidence of anti-BDC-1001 antibody (ADAs)
Exposure profile of BDC-1001 as a single agent and in combination with pertuzumab Up to 24 months Peak serum concentration (Cmax)
Trial Locations
- Locations (4)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Virginia Cancer Specialists
🇺🇸Arlington, Virginia, United States
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
City of Hope
🇺🇸Irvine, California, United States