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
Locally Advanced Breast CancerUnresectable Breast CarcinomaMetastatic Breast Cancer
Investigational drug(s) / intervention(s)
BNT323BNT327
BNT323: Intravenous infusion
BNT327: Intravenous infusion
Study 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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Part 1 - Occurrence of dose limiting toxicities (DLTs) — 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.
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 — 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.
Occurrence of dose interruption, reduction, and discontinuation due to TEAEs — 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.
Part 2 - Objective response rate (ORR) — 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.
Trial sites (79)
Facility
City
Region
Status
Beverly Hills Cancer Center
Beverly Hills
California
Recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach
California
Recruiting
Hematology - Oncology Associates of the Treasure Coast
Port Saint Lucie
Florida
Recruiting
University Cancer & Blood Center, LLC
Athens
Georgia
Recruiting
Winship Cancer Institute of Emory University
Atlanta
Georgia
Recruiting
University of Illinois Hospital & Health Sciences System
Chicago
Illinois
Recruiting
Karmanos Cancer Institute
Detroit
Michigan
Recruiting
Brigitte Harris Cancer Pavilion BHCP
Detroit
Michigan
Recruiting
START Midwest, LLC
Grand Rapids
Michigan
Recruiting
Saint Luke's Hospital of Kansas City
Kansas City
Missouri
Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
Memorial Sloan Kettering Cancer Center Basking Ridge
Basking Ridge
New Jersey
Recruiting
Summit Medical Group
Florham Park
New Jersey
Recruiting
Memorial Sloan Kettering Cancer Center Monmouth
Middletown
New Jersey
Recruiting
Memorial Sloan Kettering Cancer Center Bergen
Montvale
New Jersey
Recruiting
Memorial Sloan Kettering Cancer Center Westchester
Harrison
New York
Recruiting
Beth Israel Comprehensive Cancer Center
New York
New York
Recruiting
Mount Sinai Medical Center
New York
New York
Recruiting
Icahn School of Medicine at Mount Sinai PRIME
New York
New York
Recruiting
Memorial Sloan Kettering Hospital
New York
New York
Recruiting
Memorial Sloan Kettering Commack
New York
New York
Recruiting
Stony Brook University Hospital
Stony Brook
New York
Recruiting
Memorial Sloan Kettering Cancer Center Nassau
Uniondale
New York
Recruiting
SCRI Oncology Partners
Nashville
Tennessee
Recruiting
Baylor Scott & White Research Institute -Texas Oncology
Dallas
Texas
Recruiting
UT Southwestern Medical Center
Dallas
Texas
Recruiting
South Texas Accelerated Research Therapeutics (START), LLC
San Antonio
Texas
Recruiting
Cancer Research SA
Adelaide
Australia
Recruiting
Box Hill Hospital
Box Hill
Australia
Recruiting
St Vincent s Hospital Melbourne
Fitzroy
Australia
Recruiting
CIUSSS du Saguenay-Lac-Saint-Jean
Chicoutimi
Canada
Recruiting
London Health Sciences Centre (LHSC) - Victoria Hospital
London
Canada
Recruiting
Sunnybrook Health Sciences Centre
Toronto
Canada
Recruiting
BC Cancer - Vancouver
Vancouver
Canada
Recruiting
The First Affiliated Hospital of Bengbu Medical College
Bengbu
China
Recruiting
Jilin Cancer Hospital
Changchun
China
Recruiting
Sichuan Cancer Hospital
Chengdu
China
Recruiting
Sichuan Provincial People's Hospital
Chengdu
China
Recruiting
The First Affiliated Hospital of Chongqing Medical University
Chongqing
China
Recruiting
Huizhou First Hospital
Huizhou
China
Recruiting
+ 39 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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