A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer

May 13, 2026 updated by: BioNTech SE

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

This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study consists of two parts:

  • Part 1 - Dose escalation: In this part of the study, participants with histologically confirmed, chemotherapy-pretreated advanced HR+, HER2-low or HER2-ultralow BC will receive BNT323 in combination with BNT327 (BNT323 + BNT327) in a dose escalation design. This will define the recommended Phase 2 dose (RP2D) for the BNT323 + BNT327 combination therapy.
  • Part 2 - Dose optimization and exploratory cohorts: This part of the study will be an expansion phase, aiming to evaluate the efficacy and safety of the optimal dose combination and providing a more robust comparison against the other treatments. It will start once the enrollment in Part 1 is completed and the sponsor in conjunction with the Safety Review Committee has assessed available Part 1 efficacy and safety data. Part 2 of the study will have four cohorts, i.e., Cohorts 1 (dose optimization cohort), and Cohorts 2, 3, and 4 (exploratory cohorts). Recruitment to Cohorts 2, 3, and 4 will begin with RP2D from Part 1 and in parallel to randomization in Cohort 1.

Randomization is planned for Cohort 1 in Part 2, i.e., participants will be randomized in 2:2:1:1 ratio into one of the four arms (Arms 1-4). No randomization is planned for any other cohort in Part 2.

Study Type

Interventional

Enrollment (Estimated)

380

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: BioNTech clinical trials patient information
  • Phone Number: +49 6131 9084
  • Email: patients@biontech.de

Study Locations

  • Canada
      • Toronto, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Health Sciences Centre
  • China
      • Bengbu, China, 233004
        • Recruiting
        • The First Affiliated Hospital Of Bengbu Medical College
      • Changchun, China, 130000
        • Recruiting
        • Jilin Cancer Hospital
      • Chengdu, China, 610072
        • Recruiting
        • Sichuan Provincial People's Hospital
      • Chengdu, China, 610041
        • Recruiting
        • Sichuan Cancer Hospital
      • Chongqing, China, 400016
        • Recruiting
        • The First Affiliated Hospital of Chongqing Medical University
      • Huizhou, China, 516003
        • Recruiting
        • Huizhou First Hospital
      • Nanning, China, 530021
        • Recruiting
        • Guangxi Medical University Affiliated Tumor Hospital
      • Shanghai, China, 201315
        • Recruiting
        • Fudan University Shanghai Cancer
      • Xi'an, China, 710004
        • Recruiting
        • The Second Affiliated Hospital of Xi an Jiaotong University
  • France
      • Le Mans, France, 72000
        • Recruiting
        • Clinique Victor Hugo - Centre Jean Bernard
      • Toulouse, France, 31059
        • Recruiting
        • Institut Claudius Regaud
  • Georgia
      • Tbilisi, Georgia, 0112
        • Recruiting
        • LLC Arensia Exploratory Medicine
  • Italy
      • Milan, Italy, 20141
        • Recruiting
        • IEO Istituto Europeo di Oncologia
  • Moldova
      • Chisinau, Moldova, 2025
        • Recruiting
        • Institute of Oncology Arensia Exploratory Medicine
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01230
        • Recruiting
        • Adana City Hospital
      • Adana, Turkey (Türkiye), 01140
        • Recruiting
        • Medical Park Seyhan Hospital
      • Ankara, Turkey (Türkiye), 06100
        • Recruiting
        • Hacettepe University Medical Faculty
      • Ankara, Turkey (Türkiye), 06800
        • Recruiting
        • Ankara City Hospital
      • Ankara, Turkey (Türkiye), 06200
        • Recruiting
        • Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital
      • Istanbul, Turkey (Türkiye), 34010
        • Recruiting
        • Koç University Hospital
      • Istanbul, Turkey (Türkiye), 31755
        • Recruiting
        • Yeditepe Üniversitesi Koşuyolu Hastanesi
      • Istanbul, Turkey (Türkiye), 34295
        • Recruiting
        • IAU Medical Park Florya Hospital
      • Konya, Turkey (Türkiye), 42080
        • Recruiting
        • Konya Necmettin Erbakan University Meram Medical Faculty
      • Mersin, Turkey (Türkiye), 33240
        • Recruiting
        • Mersin City Education and Research Hospital
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrooke s Hospital
      • Cardiff, United Kingdom, CF14 2TL
        • Recruiting
        • Velindre Cancer Centre
      • Leeds, United Kingdom, LS9 7TF
        • Recruiting
        • St James's University Hospital
      • London, United Kingdom, NW3 2QG
        • Recruiting
        • Royal Free Hospital
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden Hospital-Sutton
  • United States
    • California
      • Beverly Hills, California, United States, 90211
        • Recruiting
        • Beverly Hills Cancer Center
    • Florida
      • Port Saint Lucie, Florida, United States, 34952
        • Recruiting
        • Hematology - Oncology Associates of the Treasure Coast
    • Georgia
      • Athens, Georgia, United States, 30607
        • Recruiting
        • University Cancer & Blood Center, LLC
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute of Emory University
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START Midwest, LLC
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • Saint Luke's Hospital of Kansas City
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
    • New Jersey
      • Florham Park, New Jersey, United States, 07932
        • Recruiting
        • Summit Medical Group
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Hospital
    • Texas
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START), LLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):

  • Have pathologically documented BC that:

    • Is locally advanced, unresectable or metastatic.
    • Has a confirmed HER2 status as determined by the local laboratory as standard of care testing prior to study screening (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.
    • Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines.
  • Have measurable disease defined by RECIST v1.1.
  • Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.

Key Exclusion Criteria:

  • Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
  • Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
  • Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
  • Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.

  • Have received any of the following therapies or drugs prior to the initiation of the study:

    • Participants who have received prior treatment with BNT323.
    • Participants who received prior treatment with a programmed death-ligand 1 (PD-L1) / vascular endothelial growth factor (VEGF) bispecific antibody. Note: Prior treatment with programmed death 1 (PD-1)/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted.
    • Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
    • Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part1 - BNT323 + BNT327 combination therapy
Escalating dose levels (DLs) of BNT323 and BNT327 to define RP2D. Six DLs are planned, i.e., DL0-1, DL1-1, DL2-1, DL0-0, DL1-0, DL2-0, a combination of three different DLs for BNT323 (DL0, DL1, and DL2) and two DLs for BNT327 (DL0 and DL1).
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303
Experimental: Part 2 Cohort 1 - Arm 1 - RP2D of BNT323 + BNT327
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303
Experimental: Part 2 Cohort 1 - Arm 2 - BNT323 + BNT327
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303
Experimental: Part 2 Cohort 1 - Arm 3 - BNT323 monotherapy
BNT323 monotherapy at a fixed dose
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303
Experimental: Part 2 Cohort 1 - Arm 4 - BNT327 monotherapy
BNT327 monotherapy at a fixed dose
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Experimental: Part 2 Cohort 2 - RP2D of BNT323 + BNT327
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303
Experimental: Part 2 Cohort 3 - RP2D of BNT323 + BNT327
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303
Experimental: Part 2 Cohort 4 - RP2D of BNT323 + BNT327
Drug: BNT327
Intravenous infusion
Other Names:
  • PM8002
  • Pumitamig
Drug: BNT323
Intravenous infusion
Other Names:
  • trastuzumab pamirtecan
  • DB-1303

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1 - Occurrence of dose limiting toxicities (DLTs)
Time Frame: During the DLT evaluation period (Cycle 1), i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days
By dose level.
During the DLT evaluation period (Cycle 1), i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days
Occurrence of Treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs
Time Frame: From the time of initiation of the first dose of IMP to 90 days after the last IMP dose
In Part 1 by dose level. In Part 2 by cohort and arm.
From the time of initiation of the first dose of IMP to 90 days after the last IMP dose
Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
Time Frame: From the time of initiation of the first dose of IMP to 90 days after the last IMP dose
In Part 1 by dose level. In Part 2 by cohort and arm.
From the time of initiation of the first dose of IMP to 90 days after the last IMP dose
Part 2 - Objective response rate (ORR)
Time Frame: From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

ORR defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1] based on the investigator's assessment) is observed as best overall response.

By cohort and arm.
From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1 - ORR
Time Frame: From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

ORR defined as the proportion of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response.

By dose level.
From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.
Part 2 - Duration of response (DoR)
Time Frame: From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

DoR defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (progressive disease [PD], per RECIST v1.1 based on the investigator's assessment) or death from any cause, whichever occurs first.

By cohort and arm.
From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.
Part 2 - Disease control rate (DCR)
Time Frame: From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

DCR defined as the proportion of participants with confirmed CR, PR, or stable disease (per RECIST v1.1 based on the investigator's assessment) as best overall response.

By cohort and arm.
From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.
Part 2 - Time to response (TTR)
Time Frame: From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

TTR defined as the time from first dose of IMP to first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment).

By cohort and arm.
From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.
Part 2 Cohort 1 only - Progression free survival (PFS)
Time Frame: From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

PFS based on the investigator's assessment defined as the time from first dose of IMP to the first objective tumor progression (PD per RECIST v1.1) or death from any cause, whichever occurs first.

By arm.
From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BioNTech SE

Collaborators

DualityBio Inc.
BioNTech (Shanghai) Pharmaceuticals Co., Ltd.

Investigators

  • Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 23, 2025

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

February 10, 2025

First Submitted That Met QC Criteria

February 10, 2025

First Posted (Actual)

February 14, 2025

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 13, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BNT323-03
  • 2024-517979-20-00 (Ctis)
  • 1011776 (Other Identifier: IRAS number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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