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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05954143
• Other study ID #: BBI-20231001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 30, 2023
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: Bolt Biotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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®).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 66
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer
• Metastatic 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.
• 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.

Locations

Country	Name	City	State
Italy	Istituto Nazionale Tumori IRCCS	Napoli	Campania
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
United States	Virginia Cancer Specialists	Arlington	Virginia
United States	City of Hope	Irvine	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Bolt Biotherapeutics, Inc.	Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab	Duration of Response (DOR)	Up to 24 months
Secondary	Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab	Disease Control Rate (DCR)	Up to 24 months
Secondary	Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab	Progression-Free Survival (PFS)	Up to 24 months
Secondary	Anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab	Overall Survival (OS)	Up to 24 months
Secondary	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
Secondary	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
Secondary	Exposure profile of BDC-1001 as a single agent and in combination with pertuzumab	Trough serum concentration (Cmin)	Up to 24 months
Secondary	Exposure profile of BDC-1001 as a single agent and in combination with pertuzumab	Peak serum concentration (Cmax)	Up to 24 months
Secondary	Immunogenicity of BDC-1001 as a single agent and in combination with pertuzumab	Incidence of anti-BDC-1001 antibody (ADAs)	Up to 24 months