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).
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.
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.
Sequential
BNT323
DrugIntravenous infusion
BNT327
DrugIntravenous infusion
8
Treatment groupsSee each treatment group below.
Part 1 - Occurrence of dose limiting toxicities (DLTs)
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
In Part 1 by dose level. In Part 2 by cohort and arm.
Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
In Part 1 by dose level. In Part 2 by cohort and arm.
Part 2 - Objective response rate (ORR)
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.
Part 1 - ORR
ORR defined as the proportion of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response. By dose level.
Part 2 - Duration of response (DoR)
DoR defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (progressive disease \[PD\], per RECIST v1.1 based on the investigator's assessment) or death from any cause, whichever occurs first. By cohort and arm.
Part 2 - Disease control rate (DCR)
DCR defined as the proportion of participants with confirmed CR, PR, or stable disease (per RECIST v1.1 based on the investigator's assessment) as best overall response. By cohort and arm.
Part 2 - Time to response (TTR)
TTR defined as the time from first dose of IMP to first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment). By cohort and arm.
Click on the lead sponsor to view all of their trials.
BioNTech SE
Lead sponsor
DualityBio Inc.
Collaborator
BioNTech (Shanghai) Pharmaceuticals Co., Ltd.
Collaborator