DB-1303/BNT323

Shows activity

Also known as:

BNT-323

Cancer types include:

breast cancer liver cancer non-small cell lung cancer small cell lung cancer stomach cancer

TrialFetch AI Analysis

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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)

Active trials using DB-1303/BNT323

Found 4 active trials using this drug:

A Phase III, Randomized, Multi-site, Open-label Trial of BNT323/DB-1303 Versus Investigator's Choice of Chemotherapy in Previously Treated Patients With HER2- Expressing Recurrent Endometrial Cancer

Sponsor: BioNTech SE (industry) Phase: 3 Start date: June 10, 2025

TrialFetch AI summary: Enrolls adult women with measurable recurrent endometrial cancer (including uterine carcinosarcoma) with central HER2 IHC 1+/2+ after ≥1 platinum regimen and prior anti–PD-1/PD-L1 (randomized 2:1) or HER2 IHC 3+ (single-arm), ECOG 0–2, and no prior topoisomerase I inhibitor/ADC exposure or significant ILD/pneumonitis. Treatment is the HER2-targeted antibody–drug conjugate BNT323/DB-1303 (anti-HER2 IgG1 linked to a cleavable topoisomerase I inhibitor payload) versus investigator’s choice single-agent chemotherapy (preferably doxorubicin or paclitaxel; docetaxel allowed).

ClinicalTrials.gov ID: NCT06340568

A Phase I/II, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of BNT323 in Combination With BNT327 in Participants With Advanced Breast Cancer

Sponsor: BioNTech SE (industry) Phase: 1/2 Start date: April 23, 2025

TrialFetch AI summary: This trial enrolls patients with advanced, locally unresectable or metastatic breast cancer of any HER2 status (including HER2-positive, HER2-low, HER2-ultralow, HER2-negative/triple-negative), investigating the combination of BNT323 (a HER2-targeted antibody-drug conjugate delivering a topoisomerase I inhibitor) and BNT327 (a bispecific antibody targeting PD-L1 and VEGF-A), with some arms evaluating each agent as monotherapy. Eligible patients are generally pretreated with chemotherapy and must have measurable disease.

ClinicalTrials.gov ID: NCT06827236

A Phase 3, Randomized, Multi-center, Open-Label Study of DB-1303 Versus Investigator's Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-Low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02)

Sponsor: DualityBio Inc. (industry) Phase: 3 Start date: Jan. 18, 2024

TrialFetch AI summary: This trial enrolls patients with HR+, HER2-low metastatic breast cancer who have progressed after endocrine therapy and have not received prior chemotherapy for metastatic disease or anti-HER2 therapy, randomizing them to either DB-1303 (a HER2-targeted antibody-drug conjugate with a topoisomerase I inhibitor payload) or standard single-agent chemotherapy.

ClinicalTrials.gov ID: NCT06018337

A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303/BNT323 in Patients With Advanced/Metastatic Solid Tumors

Sponsor: DualityBio Inc. (industry) Phase: 1/2 Start date: Jan. 31, 2022

TrialFetch AI summary: Adults with advanced or metastatic solid tumors expressing HER2 (including HER2-low), who are refractory or intolerant to standard therapies, receive the investigational HER2-targeted antibody-drug conjugate DB-1303/BNT323 (anti-HER2 IgG1 linked to a DNA topoisomerase I inhibitor) IV every 3 weeks; select cohorts also examine combinations with pertuzumab or CYP inhibitors for drug-drug interaction assessment.

ClinicalTrials.gov ID: NCT05150691