Duality Biologics and BioNTech presented positive interim data from a Phase 1/2a clinical trial of BNT324/DB-1311, an investigational antibody-drug conjugate (ADC) targeting B7-H3, at the ESMO Asia Congress 2024. The study, involving heavily pretreated patients with advanced solid tumors, including small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), and castration-resistant prostate cancer (CRPC), showed encouraging antitumor activity and a manageable safety profile. These findings suggest a potential new treatment option for patients with limited alternatives.
Promising Efficacy in SCLC
Among SCLC patients who had received prior immunotherapy but no prior topoisomerase 1 inhibitor, the unconfirmed objective response rate (uORR) was 70.4% at the 9 mg/kg dose level of BNT324/DB-1311. This is a notable outcome, given the aggressive nature of SCLC and the challenges in treating relapsed or refractory disease. The overall uORR in SCLC patients (n=73) was 56.2%, with a disease control rate (DCR) of 89.0%.
Activity in CRPC
BNT324/DB-1311 also demonstrated activity in CRPC, with an uORR of 28.0% and a DCR of 92.0%. The median imaging progression-free survival (rPFS) was 7.2 months, and the 6-month rPFS rate was 94.7%, indicating a potential for durable disease control in this patient population. The FDA granted Fast Track designation for BNT324/DB-1311 for the treatment of patients with advanced/unresectable, or metastatic CRPC in June 2024.
Broad Tumor Activity
The Phase 1/2a trial included 277 participants across various solid tumor types. Among all evaluable patients with at least one post-baseline tumor assessment (n=238), the overall uORR was 32.4%, and the DCR was 82.4%. Other tumor types, including cervical cancer (n=4), hepatocellular carcinoma (n=12), head and neck squamous carcinoma (n=3), and melanoma (n=11), BNT324/DB-1311 also exhibited antitumor activity with uORRs of 75.0%, 25.0%, 100.0%, and 36.4%, respectively.
Safety Profile
BNT324/DB-1311 exhibited a manageable safety profile across all evaluated patients and tumor types. The most common treatment-related adverse events (TRAEs) included nausea, decreased neutrophil count, anemia, decreased white blood cell count, decreased appetite, and decreased platelet count.
Future Directions
Duality Biologics and BioNTech are planning multiple clinical trials combining selected assets from their strategic partnership. A Phase 1/2 trial evaluating BNT324/DB-1311 in combination with BNT327/PM8002, a bispecific antibody targeting PD-L1 and VEGF-A, in patients with SCLC or NSCLC is planned to start in 2025. This combination strategy aims to further enhance the antitumor activity of BNT324/DB-1311.
About BNT324/DB-1311
BNT324/DB-1311 is a next-generation ADC targeting the immune checkpoint protein B7-H3, which is overexpressed in a range of solid tumors and associated with disease progression. The FDA has granted Orphan Drug Designation to BNT324/DB-1311 for the treatment of advanced or metastatic esophageal squamous cell carcinoma in July 2024.
