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
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
Interventions
BNT323
BNT327
Conditions
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