DB-1303/BNT323

Overview

DB-1303/BNT323, now called trastuzumab pamirtecan, is an investigational HER2-directed antibody–drug conjugate (ADC) being developed by Duality Biologics and BioNTech for HER2-expressing cancers. Clinical development includes endometrial and breast cancer. Published evidence remains largely limited to conference abstracts and early-phase, non-randomized studies. (annalsofoncology.org)

Mechanism of action

The ADC comprises a humanized anti-HER2 IgG1 antibody linked through a cathepsin-cleavable tetrapeptide linker to P1003, a DNA topoisomerase-I inhibitor. Its drug-to-antibody ratio is approximately eight. Binding to HER2 is intended to deliver the cytotoxic payload preferentially to HER2-expressing tumor cells. (ascopubs.org)

Efficacy

Endometrial cancer: In a phase 2 expansion cohort of previously treated, HER2-expressing advanced endometrial cancer, independent central review found a confirmed objective response rate (ORR) of 47.9% among 96 centrally confirmed patients, a disease-control rate of 83.3%, median response duration of 11.1 months, and median progression-free survival (PFS) of 8.1 months. Responses occurred at HER2 IHC 1+, 2+, and 3+, with higher response rates at IHC 3+. Updated results from the overall 145-patient cohort reported median PFS of approximately 8.0 months and median overall survival of 15.0 months. These results are uncontrolled and require confirmation in the ongoing randomized phase 3 Fern-EC-01 trial. (sec.gov)

Breast and other solid tumors: In an earlier phase 1 dose-escalation study, 23 of 52 evaluable patients had an unconfirmed response (44.2%). Unconfirmed ORRs were 50.0% in HER2-positive breast cancer and 38.5% in HER2-low breast cancer, with isolated responses in colorectal, endometrial, ovarian, and esophageal cancers. (ascopubs.org)

A randomized phase 3 study conducted in China in previously treated HER2-positive advanced breast cancer reportedly met its PFS primary endpoint versus trastuzumab emtansine at an interim analysis, but numerical efficacy and safety results have not yet been publicly reported. (biontech.com)

Safety

In the 145-patient endometrial-cancer cohort, grade 3 or higher treatment-related adverse events occurred in 46.9%. Adjudicated grade 3 or higher interstitial lung disease (ILD)/pneumonitis occurred in 4.8%; updated reporting described any-grade ILD/pneumonitis in 21.4%, including two fatal cases. (biontech.com)

In the earlier 85-patient dose-escalation study, common adverse events included nausea, vomiting, thrombocytopenia, and anemia. Grade 3 or higher treatment-related events occurred in 12.9%; two patients developed grade 1 ILD, and no treatment-emergent deaths or dose-limiting toxicities were reported at that data cutoff. Longer exposure and larger cohorts subsequently identified a higher incidence and severity of ILD/pneumonitis. (sec.gov)

Further reading

• Phase 2 endometrial-cancer abstract, Gynecologic Oncology
• Phase 1/2 solid-tumor results, Journal of Clinical Oncology
• Fern-EC-01 phase 3 trial abstract, Journal of Clinical Oncology
• DYNASTY-Breast02 phase 3 trial design, Annals of Oncology
• ClinicalTrials.gov: phase 1/2 study NCT05150691

Last updated: Sep 2026