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

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

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®).

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer; HER2-positive Breast Cancer
• Intervention / Treatment: Drug: BDC-1001; Drug: Pertuzumab

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• United States
  • California
    • Irvine, California, United States, 92618
      • City of Hope
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BDC-1001 Single Agent; BDC-1001 administered intravenously (IV) every 2 weeks	Drug: BDC-1001; 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.
Experimental: BDC-1001 in Combination With 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.	Drug: BDC-1001; 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.; Drug: Pertuzumab; 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.; Other Names: Perjeta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per RECIST v1.1 as Assessed by Investigator	Objective Response Rate (ORR) was defined as the proportion of participants with best overall response of confirmed Complete Response (CR) or Partial Response (PR) as determined by the treating Investigator using RECIST v1.1 criteria.	Up to approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) Per RECIST v1.1 as Assessed by Investigator	Duration of Response (DOR) was calculated for participants who achieved confirmed CR or PR. For such participants, DOR is defined as the duration from the start date of CR or PR (whichever response status is observed first) and subsequently confirmed, to the earliest of documented date of PD per RECIST v 1.1 or death. Of the 8 participants with response assessments, there were no participants with PR or CR. Because there were no responses of PR or CR, the DOR cannot be calculated.	Up to approximately 1 year
Disease Control Rate (DCR) Per RECIST v1.1 as Assessed by Investigator	Disease Control Rate (DCR) was the proportion of participants who achieved confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) lasting 23 or more weeks following the first dose of study treatment.	Up to approximately 1 year
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Investigator	Progression-free survival (PFS) was defined as the duration from the date of first study treatment administration (Cycle 1 Day 1) to the earliest date of documented PD per RECIST v1.1 or death. A death was considered a PFS event.	Up to approximately 1 year
Overall Survival (OS)	Overall Survival (OS) was defined as the duration from the date of first study treatment administration to the date of death, irrespective of cause.	Up to approximately 1 year
Number of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)	Treatment Emergent Adverse Events (TEAE) was defined as any AE that started on or after the first administration of study treatment. TEAEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	Continuously from first dose of study treatment through end of treatment and Safety Follow-Up. Up to approximately 1 year
Number of Participants Who Had Any Treatment Emergent Adverse Event (TEAE) Related to Study Treatment	Treatment Emergent Adverse Events (TEAE) was defined as any AE that started on or after the first administration of study treatment. TEAEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	Continuously from first dose of study treatment through end of treatment and Safety Follow-Up. Up to approximately 1 year.
Number of Participants With Any Treatment Emergent Serious Adverse Event (SAE) Related to Study Treatment	Treatment Emergent Adverse Events (TEAE) was defined as any AE that started on or after the first administration of study treatment. TEAEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. A Serious Adverse Event (SAE) was defined as an AE event that resulted in death, was life-threatening, required or prolongs hospitalization, caused persistent or significant disability or incapacity, resulted in congenital anomalies or birth defects, or was an important medical event.	Continuously from first dose of study treatment through end of treatment and Safety Follow-Up. Up to approximately 1 year.

Collaborators and Investigators

• Sponsor: Bolt Biotherapeutics, Inc.
• Collaborators: Hoffmann-La Roche
• Investigators: Study Director: Bolt Clinical Development, Bolt Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Actual): September 20, 2024
• Study Completion (Actual): September 25, 2024

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; pertuzumab
• Other Study ID Numbers: BBI-20231001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No