Bolt Biotherapeutics, Inc. reported positive topline data from the company's recently completed dose-escalation study of BDC-1001 in HER2-expressing solid tumors that support advancing into two Phase 2 studies. BDC-1001 is an investigational Immune-Stimulating Antibody Conjugate (ISAC) in development for the treatment of patients with HER2-expressing cancer. Data will be presented at an upcoming medical meeting.

  Topline findings from this trial indicate that BDC-1001 was well tolerated at all dose levels and schedules evaluated, both as monotherapy and in combination with nivolumab. Target drug exposure levels were achieved at or near the recommended Phase 2 dose (RP2D) by more frequent administration including every other week (q2w) and weekly (q1w) administration schedules. Anti-tumor activity was observed in the form of multiple partial responses (PRs), tumor shrinkage, and long-term stable disease at or near the RP2D across multiple HER2-expressing solid tumor types in monotherapy and in combination with nivolumab.

Moreover, biomarker data demonstrate that corresponding clinical and safety data are related to the ISAC mechanism. These data support the selection of a RP2D and advancement to Phase 2 studies. Bolt Biotherapeutics' Phase 1 dose-escalation trial enrolled more than 100 patients with 16 different HER2-expressing solid tumor types.

At enrollment, all patients entered in the study had evidence of tumor progression following prior standard of care treatments, and a majority of the patients were heavily pre-treated. BDC-1001 Phase 2 Clinical Program: Bolt's Phase 2 clinical plan includes two distinct studies, each using a Simon two-stage design. These studies will build upon Bolt's existing clinical sites and clinical trial centers of excellence in the U.S. and South Korea, expanding into multiple countries in Europe, and include: Phase 2 dose expansions of the current Phase 1/2 trial will initially focus on investigating BDC-1001 as a monotherapy, given the positive single-agent clinical data seen in the Phase 1 trial, enrolling HER2-positive colorectal, endometrial, and gastroesophageal cancer patients.

Combination arms with nivolumab are expected to initiate in each indication following demonstration of monotherapy anti-tumor activity. Bristol Myers Squibb, Bolt's clinical collaborator for this study, will continue to supply nivolumab at no cost for such expansion cohorts. Initiation of a two-cohort Phase 2 clinical trial exploring BDC-1001 as monotherapy and BDC-1001 in combination with pertuzumab in patients with HER2-positive metastatic breast cancer who have developed tumor progression following treatment with Enhertu.