Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy
A Phase II, Multi-site, Randomized, Open-label Clinical Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of BNT327 at Two Dose Levels in Combination With Chemotherapeutic Agents as First- and Second-line Treatment in Triple-negative Breast Cancer
1 other identifier
interventional
83
4 countries
31
Brief Summary
This study is a Phase II, multi-site, randomized, open-label clinical study to evaluate the safety, efficacy, and pharmacokinetics (PK) of BNT327 at two dose levels in combination with chemotherapeutic agents in the first- and second-line treatment of participants with locally advanced/metastatic triple-negative breast cancer (mTNBC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2024
Longer than P75 for phase_2
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 3, 2024
CompletedFirst Posted
Study publicly available on registry
June 7, 2024
CompletedStudy Start
First participant enrolled
August 26, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2029
February 25, 2026
February 1, 2026
3.9 years
June 3, 2024
February 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Occurrence of treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs), treatment emergent serious adverse events (SAEs)
In the combination treatment regimen according to the (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE version 5.0). By treatment arm and overall.
up to 100 days after the last dose of treatment
Occurrence of dose interruption, dose reduction, and discontinuation of study treatment due to adverse events (AEs)
By treatment arm and overall.
up to 100 days after the last dose of treatment
Objective Response Rate (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 \[RECIST 1.1\] based on the investigator's assessment) is observed as best overall response. By treatment arm.
Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
Best percentage change from baseline in the tumor size
Based on the investigator's tumor assessment according to RECIST 1.1. Defined as the change from baseline in percent to the minimal tumor size until tumor progression/recurrence or death (whichever occurs first). By treatment arm.
Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
Proportion of participants who have achieved early tumor shrinkage
Defined as ≥10% decrease in the pretreatment sum of diameters at first post-treatment tumor scan in target lesions. By treatment arm.
up to 4 months after first dose of treatment
Secondary Outcomes (11)
PK assessment: Maximum concentration (Cmax) derived from serum concentration of BNT327
from pre-dose to 15 days after study treatment
PK assessment: Area Under the Curve During the Dosing Interval (AUCtau) derived from serum concentration of BNT327
from pre-dose to 15 days after study treatment
Incidence of detectable BNT327 antidrug antibodies in serum
from pre-dose to 100 days after last dose of study treatment
ORR as assessed by the investigator
Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
Duration of Response (DOR)
Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
- +6 more secondary outcomes
Study Arms (5)
Cohort 1 Arm 1 - BNT327 DL1 + Nab-paclitaxel
EXPERIMENTALCohort 1 Arm 2 - BNT327 DL2 + Nab-paclitaxel
EXPERIMENTALCohort 2 Arm 1 - BNT327 Optimized dose + Paclitaxel
EXPERIMENTALCohort 2 Arm 2 - BNT327 Equivalent Q3W dose + Gemcitabine + Carboplatin
EXPERIMENTALCohort 2 Arm 3 - BNT327 Equivalent Q3W dose + Eribulin
EXPERIMENTALInterventions
IV infusion
IV infusion
Eligibility Criteria
You may qualify if:
- Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
- Male or female, aged ≥18 years at the time of giving informed consent.
- Are willing and able to comply with scheduled visits, the treatment schedule, the planned study assessments (including participant completed diaries) and other requirements of the study. This includes that they are able to understand and follow study-related instructions.
- Have confirmed locally recurrent inoperable or mTNBC as defined by the most recent American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines. Note, participants initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer must have histological confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis site.
- Systemic treatment naïve locally advanced/metastatic participants are eligible if:
- They have received no prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, immunotherapy, or investigational agents.
- They have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months has elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, or date of last radiation therapy, whichever occurred last) and first documented local or distant disease recurrence. This also includes participants initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer prior to TNBC diagnosis.
- Participants who received one prior systemic therapy in the locally advanced/metastatic setting are eligible if:
- They have received one systemic chemotherapy in the metastatic setting and have progressed on first line therapy. Radiographic progression must have been documented. Radiographic progression is defined as unequivocal progression of existing tumor lesions or developing new tumor lesions as assessed by the investigator.
- They have had a recurrence-free interval of ≥6 months if they have received treatment with curative intent in the past. A recurrence-free interval of ≥6 months is required for all participants (both first- and second-line treatment settings) who have received prior treatment for breast cancer with curative intent.
- Have provided a tissue sample, archival or fresh, during the screening period (bone biopsies, fine needle aspiration biopsies, and samples from pleural or peritoneal fluid are not acceptable; participants with only one target lesion are not eligible to provide a biopsy). If an archival tumor sample is not available, the participant must undergo a fresh biopsy, if medically feasible to be eligible for the study.
- Have at least one measurable lesion as the targeted lesion based on RECIST version 1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Have a minimum life expectancy of \>3 months.
- Have adequate organ function, as defined below:
- +17 more criteria
You may not qualify if:
- Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the study or within 6 months after the last dose of IMP.
- Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the study, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol described requirements.
- Have received any of the following therapies or drugs prior to the initiation of study:
- Participants who received prior treatment with a PD(L)-1/Vascular Endothelial Growth Factor bispecific antibody.
- Have received a systemic anticancer regimen within 4 weeks prior to the initiation of study treatment or have received palliative radiotherapy within 7 days prior to the initiation of study treatment, or have received any other chemotherapy, curative/palliative radiotherapy, biologic therapy (including tumor vaccines, cytokines, or growth factors for tumor control) or any experimental antitumor drugs within 4 weeks prior to the initiation of study treatment.
- Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-alpha \[IFN-α\], interleukin-2 \[IL-2\], 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.
- Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of study treatment.
- Received broad-spectrum IV antibiotics therapy within 3 weeks prior to initiation of study treatment.
- Use of any non-study investigational medicinal product within five half-lives of first dose or within 4 weeks, whichever is longer, before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
- Have undergone major organ surgery (core needle biopsies are allowed \>7 days prior study start), significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of study treatment or plan to undergo elective surgery during the study. Placement of vascular infusion devices is allowed.
- Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
- Have spinal cord compression or central nervous system metastases that is untreated and symptomatic or requires treatment with corticosteroids or anticonvulsants for associated-symptom control. Exception: Treated brain metastases which is no longer symptomatic and for which no corticosteroid or anticonvulsant treatment is needed (the participant must be recovered from the acute toxic effect of radiotherapy; study treatment assignment must be ≥2 weeks after completion of radiotherapy).
- Have active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Those who had a history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for those with clinically stable autoimmune thyroid disease or type 1 diabetes.
- Have had other malignant tumors within 2 years prior to the study treatment are not allowed. Except for those: who have been cured with local treatment (such as basal cell or squamous cell carcinoma of the skin, superficial or non-invasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary carcinoma of thyroid; including prostate cancer with CR within the past 3 years).
- +30 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BioNTech SElead
- Bristol-Myers Squibbcollaborator
Study Sites (31)
Beverly Hills Cancer Center
Beverly Hills, California, 90211, United States
Valkyrie Clinical Trials
Los Angeles, California, 90067, United States
Stanford University School of Medicine - Stanford Cancer Institute (SCI) - Stanford Women's Cancer Center
Palo Alto, California, 94304-2201, United States
Saint John's Health Center - John Wayne Cancer Institute (JWCI)
Santa Monica, California, 90404-2312, United States
Rocky Mountain Cancer Centers (RMCC)
Denver, Colorado, 80220, United States
Yale University - Yale Cancer Center
New Haven, Connecticut, 06520, United States
Carle Foundation Hospital d/b/a Carle Cancer Center
Urbana, Illinois, 61801, United States
HealthPartners Regions Specialty Clinics
Saint Louis Park, Minnesota, 55426, United States
Rutgers Cancer Institute of NJ (Rutgers, The State University of New Jersey)
New Brunswick, New Jersey, 08901, United States
Stony Brook University Hospital
Stony Brook, New York, 11794, United States
The West Clinic, P.C. d/b/a West Cancer Center
Germantown, Tennessee, 38138, United States
SCRI Oncology Partners
Nashville, Tennessee, 37203, United States
Bon Secours St. Francis Medical Center
Midlothian, Virginia, 23114, United States
Peninsula Oncology Centre
Frankston, 3199, Australia
Peter MacCallum Cancer Centre
Melbourne, 3050, Australia
Baskent Universitesi Tip Fakultesi Adana Hastanesi
Adana, 01120, Turkey (Türkiye)
Medical Park Seyhan Hospital
Adana, 01230, Turkey (Türkiye)
Sakarya University - Faculty of Medicine
Adapazarı, 54290, Turkey (Türkiye)
Hacettepe Universitesi Kanser Enstitusu
Ankara, 06100, Turkey (Türkiye)
Sbu Dr.A.Y. Ankara Onkoloji SUAM
Ankara, 06100, Turkey (Türkiye)
Memorial Ankara Hospital
Ankara, 06520, Turkey (Türkiye)
Koc Universitesi Hastanesi (Koc University Hospital)
Istanbul, 34010, Turkey (Türkiye)
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
Istanbul, 34093, Turkey (Türkiye)
Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, 34722, Turkey (Türkiye)
Yeditepe University Hospital
Istanbul, 34755, Turkey (Türkiye)
Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
Cottingham, HU16 5JQ, United Kingdom
Edinburgh Cancer Centre-Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
St James's University Hospital - Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF, United Kingdom
St Bartholomew's Hospital - Barts Health NHS Trust
London, EC1A 7BE, United Kingdom
Sarah Cannon Research Institute
London, W1G 6AD, United Kingdom
University College London Hospitals NHS Foundation Trust
London, W1T 7HA, United Kingdom
Related Publications (1)
Biteghe FAN, Mungra N, Malindi Z, Chalomie NET, Stanislas KA, Yasmin-Karim S, Mike Makrigiorgos G, Chipidza FE, Akinrinmade OA, Sridhar S, Barth S, Ngwa W. The Therapeutic Potential of Photoimmunotherapy as a Safe, Effective and Non-Toxic Treatment Option for Superficial Triple Negative Breast Cancer. Cancer Med. 2025 Sep;14(18):e71255. doi: 10.1002/cam4.71255.
PMID: 40970572DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
BioNTech Responsible Person
BioNTech SE
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 3, 2024
First Posted
June 7, 2024
Study Start
August 26, 2024
Primary Completion (Estimated)
August 1, 2028
Study Completion (Estimated)
June 1, 2029
Last Updated
February 25, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share