Phase 2 Evaluating BDC-1001 Plus Perjeta in HER2-Positive Breast Cancer

The antitumor activity of immune-stimulating antibody conjugate (ISAC) BDC-1001, when combined with Perjeta (pertuzumab), in various HER2 tumor-expressing cancers, including breast cancer, will be evaluated in a phase 2 trial. This trial includes patients with histologically confirmed HER2-postive breast adenocarcinoma and is designed to observe the antitumor effects of BDC-1001 with or without Perjeta, according to a poster presented at the 2023 San Antonio Breast Cancer Symposium (SABCS).

“BDC-1001 was well-tolerated in the phase 1 dose-escalation trial that enrolled patients with HER2-expressing solid tumors. Clinical activity observed across different HER2-positive tumor types and in a heterogenous, heavily pretreated patient population: 29% response rate in HER2 evaluable HER2-positive tumors at the recommended phase 2 dose; multiple patients with long-term stable disease,” investigators reported in the poster.

The phase 2 trial is an open-label, multicenter study, and patients with HER2-positive metastatic breast cancer will be randomly assigned into two arms.

The first arm will receive single-agent BDC-1001 intravenously (IV) every two weeks at 20 mg/kg, which was based on safety, clinical efficacy and pharmacokinetics (how the drug moves through and is absorbed in the body) reported from the phase 1 trial.

The second arm will receive the same dose of BDC-1001 every two weeks in combination with an 840 mg/420 mg dose of intravenous Perjeta administered every three weeks.

The primary endpoint of the trial was the objective response rate (patients whose disease responded partially or completely to treatment). Secondary endpoints include evaluating antitumor activity in response to BDC-1001 with or without Perjeta regarding duration of response, disease control rate (patients whose disease shrunk, disappeared or was stable from treatment), progression-free survival (how long a patient lives without their disease spreading or worsening) and overall survival (how long a patient lives following treatment, regardless of disease status) as well as determining safety, tolerability, pharmacokinetics and immunogenicity (the ability for tissues and cells to provoke an immune response.

To be eligible for the phase 2 trial, patients with histologically confirmed HER2-positive breast adenocarcinoma must have been treated previously with Enhertu (trastuzumab deruxtecan) and at least one other prior anti-HER2 therapy.

Prior neoadjuvant (before surgery) or adjuvant (following the main treatment) therapy that resulted in relapse within 12 months of completion of therapy will also be considered as a prior line of treatment.

Patients must have an ECOG performance status of 0 or 1 (patients can perform all of their daily tasks with little to no help) and must agree to biopsy before enrollment in the trial unless the biopsy cannot be accessed safely or clinically feasibly.

Specific exclusions for eligibility are if the patient has a history of treatment with a TLR7, TLR8 or has received a TLR7/8 agonist within 12 months of enrollment. Patients with central nervous system metastases are eligible for the study unless the disease is asymptomatic, clinically stable and hasn’t required steroid treatment for at least 28 days before starting the study treatment.

To assess whether there is a relationship between specific markers found in both the blood and tumor tissue before treatment and how BDC-1001, either alone or combined with Perjeta, works against the tumor, tissue biopsies will be taken at baseline and after treatment.

Pro-inflammatory cytokines and chemokines will also be evaluated as well as examining additional biomarkers in tumor tissue and blood related to tumor and immune biology. This involves analyzing gene expression, mutations, proteins, and tissue images to better understand the biological aspects of the tumor and immune system.

The decision to proceed with the phase 2 trial was based on data received from the phase 1 trial, focusing on dose escalation for patients with HER2 breast cancer. Within phase 1, 131 patients with 16 various unspecified HER2 solid tumor expressions received an increasing 0.5 to 20 mg/kg dose of BDC-1001.

The treatment was tolerated as both a monotherapy and when combined with Opdivo (nivolumab), all patients showed clinical activity across different HER2-positive tumor types in both the heterogenous and heavily treated patient population.

Preclinical research showed that combining a surrogate of BDC-1001 with Perjeta improves the effectiveness against various HER2-expressing tumor models. This formed the basis for considering the combination therapy of BDC-1001 and Perjeta. With the addition of Perjeta, the agent attaches to a different location on the HER2 tumor and boosts the quantity of antibodies attached to the tumor cell surface.

“Enrollment of the phase 2 study is ongoing in the United States, France, Italy and Spain,” investigators stated in the poster.

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