Bolt presents updated clinical data from Phase 1 trial of BDC-1002

Bolt Biotherapeutics presented updated data from its Phase 1 dose-escalation trial of BDC-1001 at the European Society for Medical Oncology 2023 Congress, being held in Madrid, Spain and virtually from October 20-24, 2023. BDC-1001 is an investigational Immune-Stimulating Antibody Conjugate in development for the treatment of patients with human epidermal growth factor receptor 2 positive cancer. BDC-1001 comprises a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to a proprietary TLR7/8 agonist. The Phase 1 dose-escalation trial enrolled 131 patients with 16 different HER2-expressing solid tumor types across 18 dose levels in two arms, monotherapy and in combination with nivolumab. 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. Key findings from the updated Phase 1 BDC-1001 dose escalation study are summarized below. Improved BDC-1001 efficacy was observed since the data presented at ASCO in June 2023 with one new CR, two additional long-term SDs, and three patients who received therapy for at least one year. At the RP2D, one CR was observed in the monotherapy arm in a patient with salivary gland cancer and three PRs were observed at the RP2D; one in the monotherapy arm in a patient with biliary tract cancer and two in the combination arm in patients with colorectal and ovarian cancer. The response rate at the RP2D was 29% in evaluable patients with HER2-positive tumors, both in monotherapy and in combination with nivolumab. At the RP2D, among evaluable patients with HER2-positive tumors, 43% in the monotherapy arm and 57% in the combination arm experienced at least 24 weeks of disease control, and 57% in the monotherapy arm and 71% in the combination arm achieved tumor shrinkage. BDC-1001 continues to be well tolerated at all dose levels and schedules as both monotherapy and in combination with nivolumab with no increase in toxicity in combination with BDC-1001. The most frequent drug-related treatment-emergent adverse events were grade 1 or 2 infusion-related reactions, which were observed in 29.8% of subjects. Grade 3 or higher treatment-related TEAEs were seen in ten subjects with only one grade 4 and no grade 5 drug-related AEs. Pharmacodynamic responses in both plasma and tissue were consistent with the mechanism of action for an ISAC. Statistically significant upregulation of TLR signaling pathway gene signature, innate immunity gene signatures and T cell inflamed phenotype was observed in the four patients with clinical benefit. Increases in innate immunity signatures was observed in patients in the q2w cohorts, but not q1w. The once-weekly dosing cohorts experienced higher rates of adverse events versus every-two-week dosing, including: grade 3 or higher BDC-1001-related TEAEs, grade 3 or higher LVEF decreases, and infusion-related reactions, providing further support for the selection of 20 mg/kg q2w as the RP2D.