BDC-1001 Receives FDA Orphan Drug Designation in Gastric Cancers

BDC-1001 is an immune-stimulating antibody conjugate trastuzumab (Herceptin) biosimilar that targets HER2 with a non-cleavable linker to a proprietary TLR7/8 agonist. It is currently being evaluated in 2 clinical phase 2 studies that include several tumor types such as HER2-positive breast, colorectal, GEJ, and endometrial cancer.

Immune-stimulating antibody conjugate (ISAC) BDC-1001 has been given orphan drug designation by the FDA for patients with gastric and gastroesophageal junction (GEJ) cancer, according to a press release from Bolt Therapeutics.¹

The agent is an ISAC trastuzumab (Herceptin) biosimilar that targets HER2 with a non-cleavable linker to a proprietary TLR7/8 agonist. BDC-1001 is currently being evaluated in 2 clinical phase 2 studies that include several tumor types such as HER2-positive breast, colorectal (CRC), GEJ, and endometrial cancer. The first study is evaluating the agent with or without pertuzumab (Perjeta) in those with HER2-positive metastatic breast cancer (NCT05954143), while the second is combining the agent with nivolumab (Opdivo; NCT04278144).

“Receiving orphan drug designation from the FDA is an important step forward in the development of BDC-1001 and reinforces the potential of BDC-1001 to address unmet needs for patients with gastric cancers,” Edith A. Perez, MD, chief medical officer at Bolt Biotherapeutics, said in the press release. “Our Boltbody™ ISAC platform is the only one with emerging clinical validation, and we are working diligently to advance our ongoing phase 2 program.”

A topline data readout from the study assessing BDC-1001 and nivolumab indicated that both the single-agent and combination regimen yielded clinical activity and appeared tolerable in those with HER2-positive solid malignancies.² Target drug exposure levels were reached at or near the recommended phase 2 dose when investigators administered BDC-1001 every other week or weekly. Moreover, investigators reported numerous partial responses, tumor shrinkage, and continuous stable disease with both the monotherapy and combination.

“While we have made remarkable progress in developing new treatments for patients with HER2-expressing cancers, there remains an urgent need for innovation,” lead investigator Bob T. Li, MD, PhD, MPH, physician ambassador to China and Asia-Pacific at Bobst International Center, co-director of the Thoracic Liquid Biopsy Program, and chief scientific officer at Memorial Sloan Kettering (MSK) Direct, MSK Cancer Center, said at the time of the data read out.²

“In this international dose-escalation trial, BDC-1001 leveraged a novel mechanism of HER2-targeted [ISAC] and demonstrated encouraging evidence of efficacy and manageable safety, providing hope of a potential new treatment option for patients with HER2-expressing tumors.”

Eligibility criteria for the BDC-1001/nivolumab study include having an advanced solid tumor and documented HER2 expression, measurable disease by RECIST 1.1 criteria, an ECOG performance status of 0 to 1, and available tumor tissue for biomarker assessment. Those with a history of severe hypersensitivity to any of the study drug ingredients were not eligible for enrollment. Additional exclusion criteria include previous treatment with a TLR7, TLR8, or TLR7/8 agonist; impaired cardiac function; or infection with human immunodeficiency virus or active hepatitis B or C.

In the BDC-1001/pertuzumab study, patients will receive BDC-1001 intravenously every 2 weeks in addition to an 840 mg intravenous loading dose of pertuzumab followed by a 420 mg maintenance dose every subsequent 3 weeks.

To be included in the study, patients need to have histologically confirmed HER2-positive breast cancer that has been treated with 2 or more prior lines of anti-HER2 therapy, one of which was in the metastatic setting and included fam-trastuzumab deruxtecan-nxki (Enhertu). Other inclusion criteria include having measurable disease, an ECOG performance status of 0 to 1, and a life expectancy of over 12 weeks.

Those who previously received treatment with a TLR7/8 agonist; have impaired cardiac function; or have infection with human immunodeficiency virus or active hepatitis B or C are unable to enroll on the study.

References

1. Bolt Biotherapeutics receives orphan drug designation for BDC-1001 for treatment of gastric cancers. News release. Bolt Biotherapeutics. September 28, 2023. Accessed October 3, 2023. https://bit.ly/45lNHm9
2. Bolt Biotherapeutics announces positive topline data from BDC-1001 phase 1 dose-escalation trial in HER2-expressing tumors, supporting advancement to phase 2 clinical studies. News release. Bolt Biotherapeutics. March 29, 2023. Accessed October 3, 2023. bit.ly/3KkCjii