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®).

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.

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.