Trial of BDC-1001 +/- Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 2, Multi-Center, Randomized, Open-Label Trial of BDC-1001 as a Single Agent and in Combination With Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer Previously Treated With Trastuzumab Deruxtecan

Conditions
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Metastatic Breast Cancer, HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: BDC-1001
* Drug: Pertuzumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BDC-1001 Single Agent<br>BDC-1001 administered intravenously (IV) every 2 weeks | Drug: BDC-1001<br>* BDC-1001 is an immune-stimulating antibody conjugate (ISAC) designed to be delivered systemically (intravenously) and act locally by targeting HER2-expressing tumors and related metastatic disease for destruction by the innate and adaptive immune systems. BDC-1001 consists of an investigational biosimilar of the humanized monoclonal antibody (mAb) trastuzumab that is chemically conjugated to a toll-like receptor (TLR)7/8 agonist (payload) with an intervening non-cleavable, cell membrane impermeable linker.<br>|
| Experimental: BDC-1001 in Combination With Pertuzumab<br>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. | Drug: BDC-1001<br>* BDC-1001 is an immune-stimulating antibody conjugate (ISAC) designed to be delivered systemically (intravenously) and act locally by targeting HER2-expressing tumors and related metastatic disease for destruction by the innate and adaptive immune systems. BDC-1001 consists of an investigational biosimilar of the humanized monoclonal antibody (mAb) trastuzumab that is chemically conjugated to a toll-like receptor (TLR)7/8 agonist (payload) with an intervening non-cleavable, cell membrane impermeable linker.<br>Drug: Pertuzumab<br>* Pertuzumab is a monoclonal antibody that targets HER2 and prevents dimerization of HER2 with other members of the HER family (HER1, HER3, and HER4), thereby blocking ligand-activated downstream signaling.<br>* Other names: Perjeta®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab | Objective Response Rate (ORR) according to RECIST v1.1 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab | Duration of Response (DOR) | Up to 24 months | 
| Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab | Disease Control Rate (DCR) | Up to 24 months | 
| Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab | Progression-Free Survival (PFS) | Up to 24 months | 
| Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab | Overall Survival (OS) | Up to 24 months | 
| Incidence of treatment-emergent events with BDC-1001 as a single agent and in combination with pertuzumab | Treatment-emergent Adverse Events (TEAEs) | Up to 24 months | 
| Incidence of treatment-emergent events with BDC-1001 as a single agent and in combination with pertuzumab | Treatment-emergent Serious Adverse Events (TESAEs) | Up to 24 months | 
| Exposure profile of BDC-1001 as a single agent and in combination with pertuzumab | Trough serum concentration (Cmin) | Up to 24 months | 
| Exposure profile of BDC-1001 as a single agent and in combination with pertuzumab | Peak serum concentration (Cmax) | Up to 24 months | 
| Immunogenicity of BDC-1001 as a single agent and in combination with pertuzumab | Incidence of anti-BDC-1001 antibody (ADAs) | Up to 24 months |