DNA | Image Credit: © Sergey Nivens - www.stock.adobe.com
The first patient with an advanced HER2-expressing solid tumor has been dosed with BDC-1001 with or without nivolumab (Opdivo), marking the initiation of the phase 2 dose-expansion portion of a phase 1/2 study (NCT04278144).1
Phase 2 dosing follows an announcement of preliminary efficacy shown with single-agent BDC-1001 or BDC-1001 in combination with nivolumab in the phase 1 portion of the study.2 In the topline analysis, anti-tumor activity was showed with multiple partial responses, cases of reduction in tumor size, and long-term stable disease. BDC-1001 was also well-tolerated in patients. Further results from a biomarker assessment showed that the mechanism of action of BDC-1001 correlates with the phase 1 findings.2
About the Phase 2 Study of BDC-1001
Trial Name: Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination With Nivolumab in Patients With Advanced HER2-Expressing Solid Tumors
ClinicalTrials.gov Identifier: NCT04278144
Sponsor: Bolt Biotherapeutics, Inc.
Recruitment Contact: Bolt Biotherapeutics, 1-650-665-9295, firstname.lastname@example.org
Completion Date: October 31, 2026
BDC-1001 is an investigational Immune-Stimulating Antibody Conjugate (ISAC). Preclinical research shows that the use of ISACs led to mouse myeloid antigen-presenting cells (APCs) stimulation in vitro. Moreover, ISAC treatment induced more intense toll-like receptor and FcyR-associated intracellular signaling in human myeloid APCs. Together, these preclinical findings suggested that an ISAC can have durable anti-tumor efficacy.3
In effort to confirm the what was shown preclinically, 390 patients with either HER2-positiv endometrial cancer, colorectal cancer, breast cancer, gastric cancer, stomach cancer, gastrointestinal cancer, non–small cell lung cancer, biliary tract cancer, head and neck cancer, urothelial cancer, or gastroesophageal cancer will be treated with BDC-1001 20 mg/kg, biweekly alone or in combination with nivolumab in the phase 1/2 study. The primary end points assessed in the phase 1 portion of study included the incidence of adverse events (AEs), the incidence of dose-limiting toxicities, the incidence of possible immune-related toxicities, the maximum-tolerated dose of BDC-1001. The primary end point to be examined in phase 2 is ORR. The study will also evaluate pharmacokinetics, duration of response, disease control rate, progression-free survival, as well as the incidence of anti-BDC-1001 antibodies, AEs and serious AEs, and possible immune-related AEs.4
Patients eligible to be enrolled in the study are adults with advanced solid tumors expression HER2, measurable disease, and ECOG performance status of 0 or 1, and available tumor tissue for biopsies. The study excludes patients who have a hypersensitivity to any component of study treatment, including to trastuzumab (Herceptin) or another monoclonal antibody. Patients are also ineligible to be enrolled in the study if they have been previously treated with TLR 7, TLR 8 or a TLR 7/8 agonist. In terms of comorbidities, the study excludes patients who have a condition impacting their cardiac function, or clinically significant cardiac disease, as well as those with human immunodeficiency virus, active SARS-CoV-2 infection, or central nervous system metastasis.
“This is an important milestone for our company that builds on the positive signal of monotherapy activity that we observed in the Phase 1 portion of the study,” said Edith A. Perez, MD, chief medical officer of Bolt Biotherapeutics, in a press release.1 “Despite considerable advances in anti-cancer therapy, HER2-positive tumors remain difficult to treat, and new therapeutic options are urgently needed. Our ISAC platform brings a novel mechanism with the potential to address refractory and recurrent disease to the treatment of HER2+ cancers and BDC-1001 has demonstrated promise. We are committed to advancing this study for the benefit of the many patients in need.”
Other studies of BDC-1001 is ongoing at sites in the United States, Europe, and Asia (NCT04278144 and NCT05954143). These trials cover the general HER2-positive solid tumor population, and HER2-positive metastatic breast cancer.
1. Bolt Biotherapeutics initiates phase 2 clinical studies of BDC-1001 in patients with HER2-positive cancer. News release. August 3, 2023. Accessed August 14, 2023. https://tinyurl.com/3rjusv65
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, Inc. March 29, 2023. Accessed April 3, 2023. https://yhoo.it/3nEFfi2
3. Ackerman SE, Gonzalez JC, Pearson CI, et al. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable anti-tumor immunity. Nat Cancer. 2021;2(1): 18-33.
4. A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in advanced HER2-expressing solid tumors. ClinicalTrials.gov. Updated February 21, 2023. Accessed August 14, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04278144?term=NCT04278144&draw=2&rank=1