Biosimilar Conjugate Evaluated in HER2-Positive Patient Population

December 9, 2020
Tony Hagen

Tony Hagen is senior managing editor for The Center for Biosimilars®.

Investigators explained the potential for durable antitumor efficacy in patients with human epidermal growth factor receptor 2 (HER2)-expressing or -driven tumors who have exhausted other treatment options.

Investigators hope to improve durability of response in human epidermal growth factor receptor 2 (HER2)-positive solid tumors with a novel trastuzumab biosimilar conjugated to a toll-like receptor 7/8 agonist and designed to activate myeloid antigen presenting cells, which alert T cells to the presence of cancerous cells and mediate an immune response.

The investigational biosimilar (BDC-1001) holds potential as an improvement on anti-HER2 monoclonal antibodies in HER2-driven or -expressing cancers. In studies of mice with tumors resistant to conventional treatment, trastuzumab-based immune-stimulating antibody conjugates have elicited potent and durable antitumor efficacy “including complete tumor regression,” investigators said in an abstract about the study presented at the 2020 San Antonio Breast Cancer Symposium.

“Importantly, BDC-1001 did not induce interstitial lung disease, cytokine release syndrome, or thrombocytopenia in primate studies," the investigators said.

The phase 1/2, first-in-human, dose-escalation and dose-expansion study will enroll up to 390 patients with HER2-expressing or HER2-amplified advanced solid tumors who have exhausted the potential for treatment with approved anti-HER2 treatments. Patients will receive BDC-1001 with or without an immune checkpoint inhibitor targeting PD-1.

The dose-escalation phase of the trial will help to determine safety and tolerability of the treatment and establish the phase 2 dose of BDC-1001 as monotherapy and in combination with an immune checkpoint inhibitor. Primary end points include incidence of adverse events, dose-limiting toxicities, and potential immune-related toxicities.

Patients will receive BDC-1001 intravenously every 3 weeks in increasing doses. The completion of the safety data portion of the trial will allow investigators to proceed with the immune checkpoint inhibitor combination component. The dose-expansion portion of the trial will evaluate both the monotherapy with BDC-1001 and the investigational agent in combination with a checkpoint inhibitor. The primary end point of the dose-expansion portion is overall response rate.

The investigators also hope to elucidate the mechanism of action for BDC-1001 and identify biomarkers to help improve selection of patients most likely to benefit from the treatment with and without checkpoint inhibitors.

Reference

Dumbrava EI, Sharma MR, Carvajal RD, et al. Phase 1/2 study of a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), BDC-1001, as a single agent and in combination with an immune checkpoint inhibitor in patients with advanced HER2-expressing solid tumors. Presented at: SABCS; December 8-11, 2020. Abstract OT-03-02. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf