Recruiting
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
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…
ClinicalTrials.gov IDNCT06827236
PhasePHASE1, PHASE2
Enrollment380
SponsorBioNTech SE
Age18 Years
SexALL
Conditions studied
Locally Advanced Breast Cancer, Unresectable Breast Carcinoma, Metastatic Breast Cancer
About this study
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).
Interventions
- Drug: BNT323 — Intravenous infusion
- Drug: BNT327 — Intravenous infusion
Primary outcomes
- 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)
- 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)
- 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)
- 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.)
Eligibility information
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 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
- Karmanos Cancer Institute, Detroit, Michigan 48201 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
Showing 10 of 79 reported sites. See the official listing for all locations.
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-30.