DB-1303/BNT323

Overview

• DB-1303/BNT323 (also “trastuzumab pamirtecan”) is a HER2‑targeting antibody–drug conjugate (ADC) being co‑developed by BioNTech and DualityBio. It has shown antitumor activity in HER2‑positive and HER2‑low solid tumors, with a development focus in breast and endometrial cancers. The FDA granted Fast Track and Breakthrough Therapy designations for advanced endometrial cancer in 2023. A China‑run phase 3 trial versus T‑DM1 in previously treated HER2‑positive metastatic/unresectable breast cancer met its primary PFS endpoint at interim analysis (September 5, 2025). (biontechse.gcs-web.com)

Mechanism of action

• ADC composed of a trastuzumab‑based humanized anti‑HER2 IgG1 linked via a cleavable tetrapeptide linker to a proprietary topoisomerase‑I inhibitor payload (P1003) with a high drug‑to‑antibody ratio (~8). The design aims to deliver a potent DNA‑damaging payload to HER2‑expressing tumor cells and may enable activity in tumors with low HER2 expression. (researchgate.net)

Efficacy

Early‑phase (phase 1/2a, NCT05150691; ASCO 2023) - Across advanced solid tumors, the ASCO abstract reported encouraging activity; in a HER2‑low breast cancer subset, unconfirmed ORR was 38.5% (5/13). (ascopubs.org) - In advanced HER2‑expressing endometrial cancer (heavily pretreated; doses 7–8 mg/kg), an unconfirmed ORR of 58.8% and unconfirmed disease control rate (DCR) of 94.1% were reported from the ongoing study and used to support Breakthrough Therapy designation. (onclive.com)

Pivotal trials - HER2‑positive breast cancer: A randomized phase 3 study in China (NCT06265428) versus T‑DM1 met its primary endpoint of PFS at a prespecified interim analysis; detailed efficacy data have not yet been publicly released. (biontechse.gcs-web.com) - HER2‑low, HR‑positive metastatic breast cancer: A global phase 3 trial (DYNASTY‑Breast02; NCT06018337) is comparing BNT323/DB‑1303 to physician’s choice chemotherapy; primary endpoint PFS. (nasdaq.com)

Safety

Phase 1/2a (ASCO 2023, n≈85 across doses up to 10 mg/kg): - No dose‑limiting toxicities observed up to 10 mg/kg. - Most common grade ≥3 treatment‑related AEs: anemia 5.9%, decreased platelets 3.5%, nausea 2.4%. - Interstitial lung disease (ILD) occurred in 2/85 (2.4%), both grade 1; no grade ≥2 ILD reported at the time; no grade 5 TEAEs. (sec.gov)

Note: Full phase 3 safety/efficacy readouts have not yet been shared; rates and profiles may evolve with larger datasets. (biontechse.gcs-web.com)

Ongoing clinical development (selected)

• NCT05150691: Phase 1/2a first‑in‑human, advanced/metastatic solid tumors including endometrial and breast cancers; multiple global sites. (ascopubs.org)
• NCT06018337 (DYNASTY‑Breast02): Phase 3 in HER2‑low, HR+ metastatic breast cancer (DB‑1303 8 mg/kg Q3W vs capecitabine, paclitaxel or nab‑paclitaxel). (oncologypro.esmo.org)
• NCT06265428: Phase 3 in HER2‑positive metastatic/unresectable breast cancer (DB‑1303 vs T‑DM1) conducted in China; primary PFS endpoint met at interim. (biontechse.gcs-web.com)
• Additional phase 3 trial comparing DB‑1303 vs single‑agent chemotherapy in metastatic breast cancer (registry example NCT06340568). (cdek.pharmacy.purdue.edu)

Further reading

• ASCO 2023 abstract (phase 1/2a first‑in‑human): Safety and efficacy of DB‑1303 in advanced/metastatic solid tumors. Journal of Clinical Oncology 41(16_suppl):3023. (ascopubs.org)
• ESMO 2024 OncologyPRO: DYNASTY‑Breast02 phase 3 trial design and summary of phase 1 data (including HER2‑low breast cohort ORR). (oncologypro.esmo.org)
• BioNTech press releases: FDA Breakthrough Therapy designation (Dec 21, 2023); phase 3 PFS met in HER2‑positive breast cancer (Sept 5, 2025). (biontechse.gcs-web.com)
• SEC/Investor materials summarizing ASCO 2023 safety data and drug construct details. (sec.gov)
• OncLive coverage of Breakthrough Therapy designation with endometrial cohort response data. (onclive.com)

Notes - Reported response rates in early studies are unconfirmed and from ongoing trials; confirmatory, peer‑reviewed full publications are pending. (ascopubs.org)

Last updated: Oct 2025