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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
11
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 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.
City of Hope
Irvine, California, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Virginia Cancer Specialists
Arlington, Virginia, United States
Hospital Universitario 12 de Octubre
Madrid, Spain
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.
Time frame: Up to approximately 1 year
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Continuously from first dose of study treatment through end of treatment and Safety Follow-Up. Up to approximately 1 year.