BNT324

Overview

BNT324 (DB-1311) is an investigational antibody–drug conjugate (ADC) targeting B7-H3, being co-developed by BioNTech and DualityBio. It is in a global first‑in‑human Phase 1/2a trial (NCT05914116) across multiple advanced solid tumors, with preliminary efficacy signals in small cell lung cancer (SCLC), non‑small cell lung cancer (NSCLC), and castration‑resistant prostate cancer (CRPC). In June 2024 the FDA granted Fast Track designation for CRPC; in July 2024 it received Orphan Drug designation for esophageal squamous cell carcinoma (ESCC). (clinicaltrials.biontech.com)

Mechanism of action

• Target: B7-H3 (CD276), an immune checkpoint protein overexpressed in many solid tumors with limited expression in normal tissues and associated with poor prognosis. (oncologypro.esmo.org)
• Construct: Humanized anti–B7‑H3 IgG1 linked via a cleavable maleimide tetrapeptide linker to a proprietary DNA topoisomerase‑I inhibitor payload (also described preclinically as P1021); drug‑to‑antibody ratio ≈6. (aacrjournals.org)
• Dosing/PK (Phase 1/2a): 3–12 mg/kg IV every 3 weeks; maximum tolerated dose (MTD) 9 mg/kg. ADC and payload exposures increased ~dose‑proportionally; ADC half‑life ~3–4 days, payload ~5 days. (oncologypro.esmo.org)

Efficacy

• All‑comers, early ESMO Asia dataset (as of May 24, 2024): Among 77 response‑evaluable patients across dose levels, unconfirmed ORR (uORR) 28.6% (95% CI 18.9–40.0) and disease control rate (DCR) 83.1%. In SCLC (n=33), uORR 45.5%; responses also observed in CRPC (n=3), NSCLC (n=3), and cholangiocarcinoma (n=1). (oncologypro.esmo.org)
• Expanded interim analysis (press release, presented at ESMO Asia 2024): Across evaluable patients (n=238), uORR 32.4% and DCR 82.4%. Subgroups: SCLC uORR 56.2% (n=73) overall; at 9 mg/kg, SCLC patients with prior immunotherapy but no prior topoisomerase‑I inhibitor had uORR 70.4%. CRPC uORR 28.0% (n=32), median radiographic PFS 7.2 months (data immature), 6‑month rPFS rate 94.7%. NSCLC non‑squamous uORR 22.0% (n=41), squamous uORR 16.0% (n=25). (en.dualitybiologics.com)
• CRPC (ASCO 2025, press release summary): In heavily pretreated CRPC, confirmed ORR 30.8% and DCR 90.4% among 52 efficacy‑evaluable patients; 6‑month rPFS rate 69.8% among 68 evaluable patients. (prnewswire.com)

Notes: Response rates above are preliminary (often unconfirmed by independent review unless stated) and from ongoing dose‑finding/expansion cohorts; maturation of PFS/DoR data is pending. (oncologypro.esmo.org)

Safety

• ESMO Asia 2024 interim (n=126 treated): Treatment‑emergent adverse events (TEAEs) in 90.5% (treatment‑related 81.0%); grade ≥3 TEAEs in 42.1% (treatment‑related 31.7%). Common any‑grade TEAEs (≥20%): nausea (46.0%; grade ≥3 2.4%), decreased neutrophil count (34.9%; 15.9%), anemia (32.5%; 7.1%), decreased platelet count (25.4%; 6.3%), decreased WBC count (23.0%; 4.8%). Dose reductions in 9.5% and discontinuations in 5.6%. (oncologypro.esmo.org)
• Company ASCO 2025 summary: most frequent AEs were gastrointestinal and hematologic; discontinuation rates were low in the CRPC cohort. (Topline description only.) (prnewswire.com)

Trial status

• Global Phase 1/2a, first‑in‑human, multicenter, open‑label study (DB‑1311‑O‑1001; NCT05914116); recruiting sites in the US, Australia, China, and Taiwan. Design includes dose escalation (accelerated titration then 3+3) and multiple tumor‑specific expansion cohorts. (aacrjournals.org)

Regulatory designations

• FDA Fast Track designation (June 24, 2024) for advanced/unresectable or metastatic CRPC progressing after standard regimens.
• FDA Orphan Drug designation (July 2024) for advanced/metastatic ESCC. (globenewswire.com)

Further reading

• AACR 2024 trial‑in‑progress abstract describing DB‑1311 construct and study design. (aacrjournals.org)
• ESMO Asia 2024 OncologyPRO abstract with early safety/efficacy and MTD details. (oncologypro.esmo.org)
• DualityBio press release summarizing expanded ESMO Asia 2024 interim outcomes across tumor types. (en.dualitybiologics.com)
• ASCO 2025 company summary highlighting CRPC cohort outcomes. (prnewswire.com)
• AACR 2023 preclinical abstract on DB‑1311 (payload P1021) and DAR optimization. (aacrjournals.org)
• BioNTech/DualityBio Fast Track designation announcement for CRPC. (globenewswire.com)

Disclaimer: Data are from ongoing early‑phase studies and company/meeting reports; results may evolve with additional follow‑up and independent review. (oncologypro.esmo.org)

Last updated: Oct 2025