BDC-1001 With or Without Nivolumab Shows Early Signs of Clinical Activity, Tolerability in HER2-Expressing Solid Tumors

Edith A. Perez, MD

BDC-1001 monotherapy and in combination with nivolumab (Opdivo) generated antitumor activity with acceptable tolerability in patients with advanced HER2-expressing solid tumors, according to topline data from the dose-escalation portion of a phase 1 trial (NCT04278144).¹

Findings showed that both the monotherapy and combination regimens were well tolerated at all dose levels and schedules evaluated. Additionally, target drug exposure levels were achieved at or near the recommended phase 2 dose (RP2D) with more frequent administration, including weekly and every other week.

Antitumor activity observed in patients with multiple types of HER2-expressing solid tumors included multiple partial responses, tumor shrinkage, and long-term stable disease at or near the RP2D.

The data support the selection of a RP2D and advancement of the drug to phase 2 studies in breast, colorectal, endometrial, and gastroesophageal cancers, according to the announcement by Bolt Biotherapeutics. Full data from the dose-escalation portion of the trial will be presented at an upcoming medical meeting.

“We are enthusiastic to be taking the next step in investigating the therapeutic promise of BDC-1001. In the study, we not only achieved target exposure levels for BDC-1001, but at those levels we saw promising signs of clinical activity as a single agent and in combination with nivolumab,” Edith A. Perez, MD, chief medical officer of Bolt Biotherapeutics, stated in a news release. “We look forward to sharing full data at an upcoming major medical conference, and to initiating a focused phase 2 program working with a diverse group of investigators in the United States and internationally. I’d like to express my gratitude to all the patients and investigators who are participating in our trial and to the incredible team at Bolt for their hard work and dedication.”

BDC-1001 is an immune-stimulating antibody conjugate comprised of a HER2-targeting biosimilar to trastuzumab (Herceptin) conjugated to a proprietary TLR 7/8 agonist to maximize the potential antitumor response.2

The phase 1 trial enrolled patients with advanced solid tumors with documented HER2 expression or gene amplification for which approved therapies have been exhausted or are not clinically indicated.3 Patients were also required to have measurable disease per RECIST v.1.1 criteria and an ECOG performance status of 0 or 1.

Patients were excluded from the trial if they had a history of severe hypersensitivity to any ingredient of the study drugs, including trastuzumab or other monoclonal antibody; received previous treatment with a TLR 7, TLR 8, or TLR 7/8 agonist; had impaired cardiac function or history of clinically significant cardiac disease; or they had untreated central nervous system metastases, epidural tumor, or brain metastases.

Enrolled patients received escalating doses of BDC-1001 with or without nivolumab. Primary objectives for the study included safety, dose-limiting toxicities, potential immune-related toxicities, identifying the maximum-tolerated dose, and examining overall response rate.

Phase 2 dose expansions of the current phase 1/2 trial will begin with BDC-1001 monotherapy, and it will enroll patients with HER2-positive colorectal, endometrial, or gastroesophageal cancers.1 If antitumor activity is observed in the monotherapy arms, combination arms with nivolumab are expected to initiate in each indication.

A two-cohort phase 2 clinical trial will also be initiated, which will evaluate BDC-1001 alone and in combination with pertuzumab (Perjeta) in patients with HER2-positive metastatic breast cancer who have developed tumor progression following treatment with fam-trastuzumab deruxtecan-nxki (Enhertu).

References

1. 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 March 30, 2023. https://investors.boltbio.com/news-releases/
2. Our pipeline. Bolt Biotherapeutics website. Accessed March 30, 2023. https://www.boltbio.com/pipeline-new/#bdc-1001
3. A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in advanced HER2-expressing solid tumors. ClincialTrials.gov. Updated February 21, 2023. Accessed March 30, 2023. https://clinicaltrials.gov/ct2/show/NCT04278144