A Study to Compare DB-1303/BNT323 Versus T-DM1 in Breast Cancer

A Phase III, Multicenter, Open-label, Randomized Study to Compare DB-1303 Versus T-DM1 in Patients With HER2-positive Unresectable/Metastatic Breast Cancer Who Have Been Treated With Trastuzumab and a Taxane (Dynasty-Breast01)

This study is designed to compare efficacy and safety of DB-1303/BNT323 versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer patients previously treated with trastuzumab and taxane.

Study Overview

• Status: Active, not recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: DB-1303/BNT323; Drug: T-DM1

Detailed Description

This is a randomized controlled, 2-arm, open-label, multicenter phase III study to assess the efficacy and safety of DB-1303/BNT323 versus Trastuzumab Emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2) -positive unresectable/metastatic breast cancer who have been treated with trastuzumab and taxanes. Approximately 224 patients with unresectable or metastatic HER2-positive breast cancer will be randomized 1:1 to receive DB-1303/BNT323 or T-DM1, respectively.

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • 015
    • Hefei, Anhui, China, 230001
      • 016
    • Hefei, Anhui, China, 230601
      • 029
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100039
      • 001
    • Beijing, Beijing Municipality, China, 100142
      • 010
  • Changchun
    • Jilin, Changchun, China, 130022
      • 038
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • 036
    • Xiamen, Fujian, China, 361003
      • 037
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • 023
    • Guangzhou, Guangdong, China, 510080
      • 024
    • Guangzhou, Guangdong, China, 510120
      • 026
    • Huizhou, Guangdong, China, 516001
      • 028
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • 017
    • Nanning, Guangxi, China, 530021
      • 022
  • Hainan
    • Haikou, Hainan, China, 570102
      • 043
  • Hebei
    • Baoding, Hebei, China, 071000
      • 045
    • Shijiazhuang, Hebei, China, 050011
      • 048
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150081
      • 020
  • Henan
    • Luoyang, Henan, China, 471003
      • 018
    • Zhengzhou, Henan, China, 450003
      • 006
    • Zhengzhou, Henan, China, 450052
      • 005
  • Hubei
    • Wuhan, Hubei, China, 430030
      • 011
    • Wuhan, Hubei, China, 430079
      • 009
  • Hunan
    • Changsha, Hunan, China, 410005
      • 030
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • 027
    • Nanjing, Jiangsu, China, 210029
      • 004
    • Xuzhou, Jiangsu, China, 221006
      • 044
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • 014
  • Jilin
    • Changchun, Jilin, China, 130021
      • 008
  • Liaoning
    • Dalian, Liaoning, China, 116021
      • 032
  • Shandong
    • Binzhou, Shandong, China, 256603
      • 040
    • Jinan, Shandong, China, 250013
      • 031
    • Jinan, Shandong, China, 250117
      • 047
    • Linyi, Shandong, China, 276003
      • 012
    • Yantai, Shandong, China, 264001
      • 039
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • 002
    • Shanghai, Shanghai Municipality, China, 200120
      • 046
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • 035
    • Xi’an, Shanxi, China, 710061
      • 003
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • 007
    • Neijiang, Sichuan, China, 641100
      • 041
    • Yibin, Sichuan, China, 644000
      • 034
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • 021
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830011
      • 013
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • 033
  • Zhejaing
    • Hangzhou, Zhejaing, China, 310022
      • 019
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • 025
    • Hangzhou, Zhejiang, China, 310016
      • 042

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female adults ≥ 18 years at the time of voluntary signing of informed consent.
• Pathologically confirmed unresectable or metastatic HER2 positive breast cancer previously treated with trastuzumab and taxane
• Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1.
• Presence of at least one measurable lesion according to RECIST v1.1
• Expected survival time ≥ 12 weeks.
• Patients must give informed consent to this study and voluntarily sign written informed consent form prior to the study.

Exclusion Criteria:

• Prior anti-HER2 ADC therapy.
• Previous history of interstitial lung disease/noninfectious pneumonitis/radiation pneumonitis requiring steroid therapy.
• Known serious hypersensitivity to the active ingredients of the study drug, inactive ingredients in the formulation, or other antibody drugs.
• Multiple primary malignancies within 3 years, except for adequately resected non-melanoma skin cancer, curatively treated in situ tumor, or contralateral breast cancer
• Uncontrolled infection requiring intravenous antibiotics, antiviral or antifungal agents, autoimmune disease requiring treatment, uncontrolled diabetes, hypertension, or other systemic disease that makes compliance with study procedures difficult
• Unrecovered toxicity from prior anticancer therapy, defined as toxicity (except for alopecia) not recovered to ≤Grade 1 (NCI-CTCAE v5.0) or baseline.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DB-1303/BNT323; Enrolled patients will receive DB-1303/BNT323 by intravenous (I.V.) infusion	Drug: DB-1303/BNT323; Administered I.V.
Experimental: T-DM1; Enrolled patients will receive T-DM1 by I.V. infusion	Drug: T-DM1; Administered I.V.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	Defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first	Up to approximately 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as the time from randomization to death due to any cause.	Up to approximately 24 months.
Progression Free Survival (PFS) by Investigator assessment per RECIST 1.1	Defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by investigator or death due to any cause, whichever occurs first.	Up to approximately 24 months.
Objective response rate (ORR) by BICR and investigator assessment per RECIST 1.1	Defined as the percentage of patients who have a complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR and investigator assessment.	Up to approximately 24 months.
Duration of response (DoR) by BICR and investigator assessment per RECIST 1.1	Defined as the time from first response (CR or PR) to subsequent disease progression per RECIST 1.1 as assessed by BICR and investigator assessment, or death from any cause, whichever occurs first.	Up to approximately 24 months.
PK parameters: maximum observed concentration (Cmax)	Maximum observed concentration (Cmax) of DB-1303/BNT323 Antibody-drug conjugate (ADC) and free toxin P1003, etc. after DB-1303/BNT323 administration	Up to approximately 24 months.
PK parameters: time to maximum concentration (Tmax)	Time to maximum concentration (Tmax) of DB-1303/BNT323 ADC and free toxin P1003, etc. after DB-1303/BNT323 administration	Up to approximately 24 months.
Adverse events (AEs)	Number and percentage of patients who report serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), TEAEs leading to study drug discontinuation, adverse events of special interest (AESIs) (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0[NCI-CTCAE v5.0])	Up to approximately 24 months.
Patient reported outcomes (PROs): European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - C30	Change from baseline in the functioning/symptom/global quality of life (QoL) subscales of EORTC QLQ-C30. Scale scores range from 0-100. For functioning and global QoL scales, higher scores indicate better functioning or global health status. For symptom scales, higher scores indicate greater symptom burden.	Up to approximately 24 months.
Patient reported outcomes (PROs): EORTC QLQ-BR45	Change from baseline in the functioning/symptom subscales of EORTC QLQ-BR45. Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.	Up to approximately 24 months.
Patient reported outcomes (PROs): European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L)	Change from baseline in EQ-5D-5L health state utility index score and Visual Analogue Scale (VAS) score. VAS score range from 0-100, higher scores indicate better health status.	Up to approximately 24 months.
European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L)	EQ-5D-5L health state utility index score and Visual Analogue Scale (VAS) score. The change from baseline value will be reported.	Up to approximately 24 months.
Anti-drug antibodies (ADA)	Number and percentage of patients who develop anti-drug antibody (ADA) for DB-1303/BNT323.	Up to approximately 24 months.

Collaborators and Investigators

• Sponsor: DualityBio Inc.
• Collaborators: BioNTech SE
• Investigators: Study Director: Lily Hu, DualityBio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 15, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2-positive; BC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: DB-1303-O-3001; CTR20233403 (Other Identifier: CENTER FOR DRUG EVALUATION, NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No