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

• ClinicalTrials.gov Identifier: NCT05954143
• Recruitment Status: Recruiting
• First Posted: July 20, 2023
• Last Update Posted: February 15, 2024
• Sponsor: Bolt Biotherapeutics, Inc.
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): Bolt Biotherapeutics, Inc.

Tracking Information

• First Submitted Date: June 23, 2023
• First Posted Date: July 20, 2023
• Last Update Posted Date: February 15, 2024
• Actual Study Start Date: November 30, 2023
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2023)

Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab [ Time Frame: 12 weeks ]

Objective Response Rate (ORR) according to RECIST v1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 19, 2023)

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

Original Secondary Outcome Measures (submitted: July 12, 2023)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of BDC-1001 +/- Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer
• Official Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Breast Cancer
• HER2-positive Breast Cancer

Intervention

• 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 Name: Perjeta®

Study Arms

• Experimental: BDC-1001 Single Agent
  BDC-1001 administered intravenously (IV) every 2 weeks
  Intervention: Drug: BDC-1001
• 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.
  Interventions:

  • Drug: BDC-1001
  • Drug: Pertuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 12, 2023): 66
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bolt Biotherapeutics; 1-650-434-8640; clinicaltrials@boltbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05954143
• Other Study ID Numbers: BBI-20231001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bolt Biotherapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Bolt Biotherapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Hoffmann-La Roche

Investigators

• Study Director: Bolt Clinical Development; Bolt Biotherapeutics

• PRS Account: Bolt Biotherapeutics, Inc.
• Verification Date: February 2024