BNT327 for Advanced breast cancer | Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Have pathologically documented breast cancer (BC) that: is locally advanced, unresectable or metastatic; has a confirmed human epidermal growth factor receptor 2 (HER2) status as determined by the local laboratory (Part I, Part 2 Cohorts 2 and 4) or the central laboratory (Part II 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\n- Have measurable disease defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)\n- Has left ventricular ejection fraction (LVEF) greater than or equal to 55% by either echocardiography (ECHO) or multi-gated acquisition (MUGA) within 28 days before randomization/enrollment"}

Exclusion criteria

• {"criterion_text":"- Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP\n- Have an uncontrolled intercurrent illness that would limit compliance with trial requirement or substantially increase risk of incurring adverse events (AEs)\n- 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.\n- Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroid, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening\n- Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugate (ADCs) with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan (T-DXd)\n- Participants who have previously been randomized to or received treatment in a previous trial with BNT323, regardless of treatment assignment\n- Participants who received prior treatment with a programmed death 1/ vascular endothelial growth factor (PD-L1/VEGF) bispecific antibody\n- Participants who have received other systemic immunostimulatory agents or immunosuppressive therapies within 4 weeks prior to the initiation of trial treatment or are within five half-lives of the treatment drug (whichever is longer)\n- Participants who 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 trial treatment"}

Primary endpoints

• {"endpoint_text":"- Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1), by dose level.","definition_or_measurement_approach":"Occurrence of dose limiting toxicities during Cycle 1 assessed by dose level (DLT evaluation period Cycle 1)."}
• {"endpoint_text":"- Occurrence of Treatment-emergent adverse events (TEAEs), Grade greater than or equal to 3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade greater than or equal to 3 TEAEs, and treatment-related SAEs. In Part 1 by dose level. In Part 2 by cohort and arm.","definition_or_measurement_approach":"Counts and grades of TEAEs, Grade ≥3 TEAEs, SAEs and treatment-related events categorized by dose level in Part 1 and by cohort and arm in Part 2."}
• {"endpoint_text":"- Occurrence of dose interruption, reduction, and discontinuation due to TEAEs In Part 1 by dose level. In Part 2 by cohort and arm.","definition_or_measurement_approach":"Incidence of dose interruptions, dose reductions and treatment discontinuations attributed to TEAEs, reported by dose level (Part 1) and by cohort/arm (Part 2)."}
• {"endpoint_text":"- Part 2 - Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response, by cohort and arm.","definition_or_measurement_approach":"ORR = proportion of participants with confirmed CR or PR as best overall response, assessed by cohort and arm (per RECIST 1.1 as implied in objectives)."}

Secondary endpoints

• {"endpoint_text":"- Part 1 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response, by dose level.","definition_or_measurement_approach":"ORR by dose level (confirmed CR or PR as best overall response)."}
• {"endpoint_text":"- Part 2 - Duration of response (DoR) defined as the time from first objective response to first occurrence of objective tumor progression or death from any cause, whichever occurs first, by cohort and arm.","definition_or_measurement_approach":"DoR = time from first objective response to objective tumor progression or death, by cohort and arm."}
• {"endpoint_text":"- Part 2 - Disease control rate (DCR) defined as the proportion of participants with confirmed CR, PR, or stable disease as best overall response, by cohort and arm.","definition_or_measurement_approach":"DCR = proportion with confirmed CR, PR or stable disease as best overall response, by cohort and arm."}
• {"endpoint_text":"- Part 2 - Time to response (TTR) defined as the time from first dose of IMP to first objective response, by cohort and arm.","definition_or_measurement_approach":"TTR = time from first IMP dose to first objective response, by cohort and arm."}
• {"endpoint_text":"- Part 2 Cohort 1 only - Progression free survival (PFS) based on the investigator’s assessment defined as the time from first dose of IMP to the first objective tumor progression or death from any cause, whichever occurs first, by arm.","definition_or_measurement_approach":"PFS = time from first IMP dose to first objective tumor progression or death (investigator-assessed), for Part 2 Cohort 1, by arm."}

Methods

• Dr-to-patient letter (documented in recruitment materials; country-specific versions listed: FRA/ITA/ESP)
• Patient brochure (patient-facing recruitment material; country-specific versions listed: FRA/ITA/ESP)
• Patient pre-enrolment information card (documented in recruitment materials)
• About Clinical Trials Brochure (recruitment material)
• Patient-facing subject information sheets and informed consent forms (country-specific language versions available)

France

Earliest CTIS Part Ii Submission Date

15-09-2025

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

60

Number Of Sites

5

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

28-10-2025

Latest Decision Or Authorization Date

11-11-2025

Processing Time Days

14

Number Of Sites

5

Number Of Participants

17

Spain

Earliest CTIS Part Ii Submission Date

13-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

35

Number Of Sites

10

Number Of Participants

58

Primary sponsor

Full Name

BioNTech SE

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

IQVIA Limited

Responsibilities

CRO

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central Laboratory, PD-LA, PgR, ER and MammaTyper testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety Services","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Participant Travel & Convenience Solutions","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Importer and manufacturer, performs packaging, labelling, and QP-release of finished IMP (BNT323. BNT327)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central adjudication of ILD events, Imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"HER2 IHC/ISH testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"Manufacturing (Packaging, Labelling) of IMPs (BNT323, BNT327)","organisation_type":"Pharmaceutical company"}