NEW YORK – Bolt Biotherapeutics and Bristol Myers Squibb on Wednesday said they would study Bolt's anti-HER2 therapy BDC-1001 in combination with BMS' checkpoint inhibitor nivolumab (Opdivo) in HER2-expressing solid tumors as part of an ongoing Phase I/II trial.
Bolt, based in Redwood City, California, is currently studying its immune-stimulating antibody conjugate (ISAC) BDC-1001 in a four-part Phase I/II trial that will involve 390 patients with HER2-positive or HER2-low solid tumors, including breast, gastroesophageal and colorectal cancers. The first part of the trial involves dose escalation of single-agent BDC-1001 to select the right dose for part three, in which the drug will be studied in selected advanced tumor types. In the second part of the study, BDC-1001 and a checkpoint inhibitor will be studied to establish the right dose for the fourth part, where the selected dose will be part of the combination regimen tested in patients with solid tumors.
The Phase I stage of the study began last year. The combination portion is expected to begin later in 2021. BMS will provide nivolumab for the trial, and Bolt will be responsible for costs associated with executing the study.
Bolt presented preliminary results from 20 patients in the BDC-1001 monotherapy portion of the study at the American Society of Clinical Oncology's annual meeting this year. The drug was well tolerated and showed anti-tumor activity in patients who achieved stable disease and partial responses.
BDC-1001 comprises a HER2-targeting biosimilar of trastuzumab (Genentech's Herceptin) and one of Bolt's proprietary TLR7/8 agonists to stimulate the immune system, joined by an intervening non-cleavable linker. "Our unique ISAC approach initiates an innate and an adaptive immune response that may be synergistic with BMS' innovative PD-1 inhibitor Opdivo," Bolt CEO Randall Schatzman said in a statement. "The combination of BDC-1001 and Opdivo holds potential as a treatment for cancer patients, and we welcome the opportunity to investigate this in a clinical setting."