Recruiting
Phase 1
Phase 2

BNT323 & BNT327

Sponsor:

BioNTech SE

Code:

NCT06827236

Conditions

Locally Advanced Breast Cancer

Unresectable Breast Carcinoma

Metastatic Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BNT323

BNT327

Study Details

Brief summary:

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).

Conditions

Locally Advanced Breast Cancer

Unresectable Breast Carcinoma

Metastatic Breast Cancer

Study ID

NCT06827236

Start date

Apr 23, 2025

Status verified date

Aug, 2026

Completion date

Aug, 2029

Anticipated

Primary completion date

Aug, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

380 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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).

experimental: Part 2 Cohort 1 - Arm 1 - RP2D of BNT323 + BNT327

experimental: Part 2 Cohort 1 - Arm 2 - BNT323 + BNT327

experimental: Part 2 Cohort 1 - Arm 3 - BNT323 monotherapy

BNT323 monotherapy at a fixed dose

experimental: Part 2 Cohort 1 - Arm 4 - BNT327 monotherapy

BNT327 monotherapy at a fixed dose

experimental: Part 2 Cohort 2 - RP2D of BNT323 + BNT327

experimental: Part 2 Cohort 3 - RP2D of BNT323 + BNT327

experimental: Part 2 Cohort 4 - RP2D of BNT323 + BNT327

Interventions

BNT323

Intravenous infusion

BNT327

Intravenous infusion

Primary outcome measure

  • 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 ]
  • 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 ]
  • 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 ]
  • 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. ]

Central Contacts and Locations

Central contacts

BioNTech clinical trials patient information

+49 6131 9084patients@biontech.de

Locations

Beverly Hills Cancer Center

Recruiting

Beverly Hills, California, United States, 90211

Hoag Memorial Hospital Presbyterian

Recruiting

Newport Beach, California, United States, 92663

Hematology - Oncology Associates of the Treasure Coast

Recruiting

Port Saint Lucie, Florida, United States, 34952

University Cancer & Blood Center, LLC

Recruiting

Athens, Georgia, United States, 30607

Winship Cancer Institute of Emory University

Recruiting

Atlanta, Georgia, United States, 30322

University of Illinois Hospital & Health Sciences System

Recruiting

Chicago, Illinois, United States, 60612

Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

Brigitte Harris Cancer Pavilion BHCP

Recruiting

Detroit, Michigan, United States, 48202

START Midwest, LLC

Recruiting

Grand Rapids, Michigan, United States, 49546

Saint Luke's Hospital of Kansas City

Recruiting

Kansas City, Missouri, United States, 64111

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Memorial Sloan Kettering Cancer Center Basking Ridge

Recruiting

Basking Ridge, New Jersey, United States, 07920

Summit Medical Group

Recruiting

Florham Park, New Jersey, United States, 07932

Memorial Sloan Kettering Cancer Center Monmouth

Recruiting

Middletown, New Jersey, United States, 07748

Memorial Sloan Kettering Cancer Center Bergen

Recruiting

Montvale, New Jersey, United States, 07645

Memorial Sloan Kettering Cancer Center Westchester

Recruiting

Harrison, New York, United States, 10604

Beth Israel Comprehensive Cancer Center

Recruiting

New York, New York, United States, 10011

Mount Sinai Medical Center

Recruiting

New York, New York, United States, 10019

Icahn School of Medicine at Mount Sinai PRIME

Recruiting

New York, New York, United States, 10029-6503

Memorial Sloan Kettering Hospital

Recruiting

New York, New York, United States, 10065

Memorial Sloan Kettering Commack

Recruiting

New York, New York, United States, 11725

Stony Brook University Hospital

Recruiting

Stony Brook, New York, United States, 11794

Memorial Sloan Kettering Cancer Center Nassau

Recruiting

Uniondale, New York, United States, 11553

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Baylor Scott & White Research Institute -Texas Oncology

Recruiting

Dallas, Texas, United States, 75246

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390-8896

South Texas Accelerated Research Therapeutics (START), LLC

Recruiting

San Antonio, Texas, United States, 78229

CIUSSS du Saguenay-Lac-Saint-Jean

Recruiting

Chicoutimi, Canada, G7H 5H6

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Canada, M4N 3M5

BC Cancer - Vancouver

Recruiting

Vancouver, Canada, V5Z 4E6

More Information

Sponsor

BioNTech SE

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

Keywords

  • Breast Cancer (BC)
  • Human epidermal growth factor receptor 2 (HER2)
  • IHC scores 0, 1+, 2+, and 3+
  • Antibody drug conjugate (ADC)
  • Programmed Death-1 (PD-1)
  • Programmed Death Ligand-1 (PD-L1)
  • Programmed Death-1 monoclonal antibodies
  • Anti vascular endothelial growth factor-A (anti-VEGF-A)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by BioNTech SE on 2026-08-27.