Phase III Trial of BNT327 plus Combination Chemotherapy versus Placebo plus Chemotherapy in Patients with Previously Untreated Metastatic or Locally Recurrent Triple-Negative Breast Cancer
- Trial ID
- 2025-521884-12-00
- Protocol
- BNT327-05
- Sponsor
- BioNTech SE
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase III trial is to compare overall survival in patients with triple-negative breast cancer receiving pumitamig in combination with chemotherapy versus placebo plus chemotherapy in the intent-to-treat set. Additionally, progression-free survival will be compared between the two treatment arms as assessed by blinded independent central review. Secondary objectives include the evaluation of antitumor activity through the objective response rate, duration of response, and disease control rate. Further assessments involve comparing progression-free survival rates as determined by the investigator, as well as evaluating survival rates at fixed timepoints. The study will also monitor safety and tolerability, and assess quality of life using patient-reported outcome scores.
Participants
This clinical trial involves 414 participants diagnosed with first-line triple-negative breast cancer or ER-low, HER2-negative breast cancer. The study population includes both male and female patients within specific age ranges, including vulnerable populations. Eligible participants must have documented locally recurrent inoperable or metastatic disease and at least one measurable lesion according to RECIST v1.1. Selected individuals are required to have an ECOG performance status of 0 or 1 and demonstrate adequate haematology, liver function, kidney function, and coagulation. Inclusion is further contingent upon being ineligible for combination treatment with monospecific PD(L)1 targeting immunotherapy plus chemotherapy based on tumor PD-L1 expression status. Requirements for participants of child-bearing potential involve a negative serum beta hCG pregnancy test and adherence to highly effective contraception methods.
Plans and Procedures
This Phase III, multisite, randomized, double-blind, controlled trial is designed to evaluate the efficacy and safety of pumitamig in combination with chemotherapy compared to a placebo plus chemotherapy. The study population consists of adults with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer who are ineligible for PD(L)1 therapy due to PD-L1 negative disease status. The primary objectives are to compare overall survival and progression-free survival between the two treatment arms. The research methodology involves a screening visit to confirm eligibility, including the assessment of measurable lesions and tumor tissue samples. Following randomization, participants receive treatment as assigned, followed by scheduled assessments to monitor safety and disease progression. The study is estimated to be active through May 2030. Participant involvement may be subject to early termination based on clinical requirements or specific safety protocols.
Treatment
Paclitaxel is administered at a dose of 3.8 mg/m2 via a route designated as other use.
Gemcitabine hydrochloride is provided as a solution for intravenous infusion at a dosage of 47.62 mg/m2.
Carboplatin is administered as a solution for intravenous infusion at a dose of 10.5.
BNT327 is prepared as a powder for concentrate for solution for infusion and is administered at a dose of 95.2 mg via intravenous infusion.
Paclitaxel albumin-bound is administered as a dispersion for infusion at a dose of 3.57 mg/m2.
Eribulin mesylate is administered as a solution for intravenous infusion at a dosage of 0.06 mg/m2.
A placebo for BNT327 is utilized in the study design.
Efficacy
The primary efficacy endpoints for this study in patients with triple-negative breast cancer involve overall survival, defined as the interval from randomization to death from any cause, and progression-free survival, defined as the time from randomization to the first documented tumor progression or death from any cause. Progression-free survival is assessed via blinded independent central review using RECIST v1.1. Secondary efficacy parameters include the objective response rate, which measures the proportion of patients achieving a confirmed complete response or partial response, and the duration of response, calculated from the first objective response to the first occurrence of progressive disease or death. Additionally, the disease control rate is evaluated based on confirmed complete response, partial response, or stable disease.
Further assessment includes the progression-free survival rate and overall survival rate at 6, 12, 18, and 24 months, as evaluated by both the investigator and blinded independent central review. Patient-reported outcomes are utilized to monitor changes from baseline in several domains, including the EORTC Quality of Life (QLQ)-C30 global health status and physical functioning, the arm and breast symptoms scales of the EORTC QLQ-BR42, and the Functional Assessment of Cancer Therapy - General overall bother item.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adults, of 18 years of age or older at the time of giving informed consent. Local laws will be followed if the age of consent is older.
- Are considered ineligible for combination treatment with a monospecific PD(L)1 targeting immunotherapy plus chemotherapy as per their tumor PD-L1 expression status.
- Have confirmed locally recurrent inoperable or metastatic TNBC, or ER-low, HER2-negative breast cancer documented prior to trial screening as part of standard of care and whose disease status aligns the detailed description in the protocol.
- Have at least one measurable lesion as the targeted lesion based on RECIST v1.1.
- Have provided a tissue sample, archival or fresh, during the screening period.
- ECOG performance status (PS) of 0 or 1.
- Have adequate organ function in regards to haematology, liver function, kidney function, and coagulation.
- Are people of child-bearing potential (POCBP) who have a negative serum beta hCG pregnancy test within 7 days of the start of trial treatment.
- Are POCBP who agree to practice a highly effective form of contraception and to require their male sexual partners to use barrier contraception methods (preferably condoms), starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of pumitamig or placebo.
- Are men who are sterile or if they are potentially fertile and sexually active with a partner of childbearing potential, who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the trial, starting from the time of giving informed consent and continuously until 6 months after receiving the last dose of pumitamig or placebo.
- Agree not to donate and/or cryopreserve germ cells (sperm, oocytes, ova) for the purposes of assisted reproduction during trial, from signing the informed consent form and continuously until 6 months after the last dose of pumitamig or placebo.
- Are able to give informed consent and have given written consent in accordance with ICH GCP and local legislation prior to the start of any trial-specific procedures.
- Are willing and able to comply with scheduled visits, the treatment schedule, the planned trial assessments (including patient completed diaries) and other requirements of the trial. This includes that they are able to understand and follow trial-related instructions.
Exclusion Criteria
- Have received any of the following therapies or drugs prior to the initiation of trial: • prior systemic anticancer therapy for advanced disease. • prior treatment with a PD(L)-1/VEGF bispecific antibody. • systemic corticosteroids within 7 days prior to the initiation of trial treatment. • Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of trial treatment. • Have received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of trial treatment.
- Have hypertension or diabetic conditions prior to initiation of trial treatment as defined in the study protocol.
- Have serious non-healing wounds, ulcers, or bone fractures.
- Have evidence of major coagulation disorders or other significant risks of hemorrhage as defined in the study protocol.
- Receive therapeutic anticoagulation or antiplatelet therapy.
- Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
- Have a history of serious Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy or have AEs from prior antitumor therapy that have not returned to Grade 1
- Have a known or suspected hypersensitivity to the trial treatments including any active ingredient or excipients thereof.
- Have a known history of human immunodeficiency virus with CD4+ T˗cell counts below 350 cells/µL and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
- Have a history of hepatitis B requiring active antiviral therapy.
- Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the trial, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol described requirements.
- Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the trial or within 6 months after the last dose of pumitamig or placebo.
- Have undergone major organ surgery, significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of trial treatment or plan to undergo elective surgery during the trial.
- Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
- Have spinal cord compression or central nervous system metastases that are untreated and symptomatic or require treatment with corticosteroids or anticonvulsants for associated-symptom control.
- Have active autoimmune disease that has required systemic treatment in the past 2 years
- Have had other malignant tumors within 2 years prior to the trial treatment.
- Have any heart conditions within 6 months prior to the trial treatment as described in the study protocol.
- Have an active hepatitis C virus infection.
- Are a vulnerable individual, i.e., an individual whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
- Have superior vena cava syndrome or symptoms of spinal cord compression.
- Have active, or a history of, pneumonitis requiring treatment with steroids, or active, or a history of, interstitial lung disease.
- Have a history of tuberculosis that was not successfully treated.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 23 Mar 2026 | 14 |
 Czechia | Not Yet Recruiting | 23 Mar 2026 | 10 |
 France | Not Yet Recruiting | 23 Mar 2026 | 25 |
 Germany | Recruiting | 23 Mar 2026 | 28 |
 Italy | Recruiting | 23 Mar 2026 | 17 |
 The Netherlands | Not Yet Recruiting | 23 Mar 2026 | — |
 Poland | Recruiting | 23 Mar 2026 | 40 |
 Spain | Recruiting | 23 Mar 2026 | 26 |
| Netherlands | — | — | 9 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BNT327 1-15 | Test | SOLUTION FOR INFUSION | SOLUTION FOR INTRAVENOUS INFUSION | 95.2 | 29 | PRD13349325 |
PACLITAXEL | Test | PHF00230MIG | OTHER USE | 3.8 | 29 | SCP129816 |
ERIBULIN | Test | PHF00231MIG | SOLUTION FOR INTRAVENOUS INFUSION | 0.06 | 29 | SCP101121157 |
BNT327 Placebo | Placebo | N/A | — | — | — | N/A |
CARBOPLATIN | Test | PHF00230MIG | SOLUTION FOR INTRAVENOUS INFUSION | 10.5 | 29 | SCP10337134 |
GEMCITABINE | Test | PHF00230MIG | SOLUTION FOR INTRAVENOUS INFUSION | 47.62 | 29 | SCP1128788 |
Abraxane 5 mg/ml powder for dispersion for infusion. | Test | POWDER FOR DISPERSION FOR INFUSION | OTHER USE | 3.57 | 29 | PRD9254301 |