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

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

NCT ID: NCT05954143

Condition: Metastatic Breast Cancer
HER2-positive Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Pertuzumab

Study type: Interventional

Study phase: Phase 2

Overall status: Active, not recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: BDC-1001
Description: 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.
Arm group label: BDC-1001 Single Agent
Arm group label: BDC-1001 in Combination With Pertuzumab

Intervention type: Drug
Intervention name: Pertuzumab
Description: 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.
Arm group label: BDC-1001 in Combination With Pertuzumab

Other name: Perjeta®

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: City of Hope

Address:
City: Irvine
Zip: 92618
Country: United States

Facility:
Name: Memorial Sloan Kettering Cancer Center

Address:
City: New York
Zip: 10065
Country: United States

Facility:
Name: Virginia Cancer Specialists

Address:
City: Arlington
Zip: 22205
Country: United States

Facility:
Name: Hospital Universitario 12 de Octubre

Address:
City: Madrid
Zip: 28041
Country: Spain

Start date: November 30, 2023

Completion date: March 2025

Lead sponsor:
Agency: Bolt Biotherapeutics, Inc.
Agency class: Industry

Collaborator:
Agency: Hoffmann-La Roche
Agency class: Industry

Source: Bolt Biotherapeutics, Inc.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05954143