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NCT06827236PHASE1, PHASE2Recruiting

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

BioNTech SE

Start Date

4/23/2025

Completion Date

8/1/2029

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).

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

BNT323

DRUG

BNT327

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Conditions

Locally Advanced Breast CancerUnresectable Breast CarcinomaMetastatic Breast Cancer

Locations

Beverly Hills Cancer Center

Beverly Hills, California 90211

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California 92663

United States

Hematology - Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida 34952

United States

University Cancer & Blood Center, LLC

Athens, Georgia 30607

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

United States

University of Illinois Hospital & Health Sciences System

Chicago, Illinois 60612

United States

Brigitte Harris Cancer Pavilion BHCP

Detroit, Michigan 48202

United States

START Midwest, LLC

Grand Rapids, Michigan 49546

United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri 64111

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey 07920

United States

Summit Medical Group

Florham Park, New Jersey 07932

United States

Memorial Sloan Kettering Cancer Center Monmouth

Middletown, New Jersey 07748

United States

Memorial Sloan Kettering Cancer Center Bergen

Montvale, New Jersey 07645

United States

Memorial Sloan Kettering Cancer Center Westchester

Harrison, New York 10604

United States

Beth Israel Comprehensive Cancer Center

New York, New York 10011

United States

Mount Sinai Medical Center

New York, New York 10019

United States

Icahn School of Medicine at Mount Sinai PRIME

New York, New York 10029-6503

United States

Memorial Sloan Kettering Hospital

New York, New York 10065

United States

Memorial Sloan Kettering Commack

New York, New York 11725

United States

Stony Brook University Hospital

Stony Brook, New York 11794

United States

Memorial Sloan Kettering Cancer Center Nassau

Uniondale, New York 11553

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Baylor Scott & White Research Institute -Texas Oncology

Dallas, Texas 75246

United States

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas 78229

United States

Cancer Research SA

Adelaide, 5000

Australia

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5

Canada

The First Affiliated Hospital of Bengbu Medical College

Bengbu, 233004

China

Jilin Cancer Hospital

Changchun, 130000

China

Sichuan Cancer Hospital

Chengdu, 610041

China

Sichuan Provincial People's Hospital

Chengdu, 610072

China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, 400016

China

Huizhou First Hospital

Huizhou, 516003

China

Guangxi Medical University Affiliated Tumor Hospital

Nanning, 530021

China

Fudan University Shanghai Cancer

Shanghai, 201315

China

The Second Affiliated Hospital of Xi an Jiaotong University

Xi'an, 710004

China

Clinique Victor Hugo - Centre Jean Bernard

Le Mans, 72000

France

ICO - Site René Gauducheau

Saint-Herblain, 44800

France

Institut Claudius Regaud

Toulouse, 31059

France

LLC Arensia Exploratory Medicine

Tbilisi, 0112

Georgia

Azienda Ospedaliera Universitaria Policlinico Sant Orsola Malpighi IRCCS

Bologna, 40138

Italy

IEO Istituto Europeo di Oncologia

Milan, 20141

Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168

Italy

Institute of Oncology Arensia Exploratory Medicine

Chisinau, 2025

Moldova

Hospital HM Nou Delfos

Barcelona, 08023

Spain

NEXT Barcelona

Barcelona, 08023

Spain

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

MD Anderson Cancer Centre

Madrid, 28033

Spain

Centro Integral Oncologico Clara Campal

Madrid, 28050

Spain

NEXT Madrid

Pozuelo de Alarcón, 28223

Spain

Medical Park Seyhan Hospital

Adana, 01140

Turkey (Türkiye)

Adana City Hospital

Adana, 01230

Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, 06100

Turkey (Türkiye)

Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital

Ankara, 06200

Turkey (Türkiye)

Ankara City Hospital

Ankara, 06800

Turkey (Türkiye)

Yeditepe Universitesi Kosuyolu Hastanesi

Istanbul, 31755

Turkey (Türkiye)

Koc University Hospital

Istanbul, 34010

Turkey (Türkiye)

IAU Medical Park Florya Hospital

Istanbul, 34295

Turkey (Türkiye)

Konya Necmettin Erbakan University Meram Medical Faculty

Konya, 42080

Turkey (Türkiye)

Mersin City Education and Research Hospital

Mersin, 33240

Turkey (Türkiye)

Addenbrooke s Hospital

Cambridge, CB2 0QQ

United Kingdom

Velindre Cancer Centre

Cardiff, CF14 2TL

United Kingdom

St James's University Hospital

Leeds, LS9 7TF

United Kingdom

Royal Free Hospital

London, NW3 2QG

United Kingdom

Royal Marsden Hospital

London, SW36JJ

United Kingdom

The Christie Hospital

Manchester, M20 4BX

United Kingdom

Royal Marsden Hospital-Sutton

Sutton, SM2 5PT

United Kingdom