A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-Breast02)
Breast Cancer
Unknown Primary
18 Years and older, Male and Female
DB-1303-O-3002 (primary)
NCI-2024-02685
CTR20233708
Summary
The goal of this clinical trial is to assess the efficacy of DB-1303/BNT323 compared with
investigator's choice chemotherapy in terms of progression-free survival (PFS) by blinded
independent central review (BICR) in the HR+, HER2-low (immunohistochemistry [IHC]2+/in
situ hybridization [ISH]- and IHC 1+) population.
Objectives
The study is a Phase III, Randomized, Multi-center, Open-label study in HER2-low, HR+
metastatic breast cancer subjects whose disease has progressed on at least 2 lines of
prior ET or within 6 months of first line ET + Cyclin-dependent kinase (CDK) 4/6
inhibitor in the metastatic setting. The primary purpose of the study is to determine the
efficacy and safety of DB-1303/BNT323 compared with investigator's choice single agent
chemotherapy in the target population. Approximately 532 subjects with HER2 IHC 2+/ISH-
and IHC 1+ (HER2-low] expression will be randomized 1:1 across approximately 230 centers
globally to receive either DB-1303 or investigator's choice single agent chemotherapy
(capecitabine, paclitaxel or nab-paclitaxel) until Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 defined disease progression (PD), unless there is unacceptable
toxicity, withdrawal of consent, or another criterion for discontinuation is met.
Eligibility
- Male or female adults (defined as = 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).
- Pathologically documented breast cancer that: 1) Is advanced or metastatic 2) Has HER2-low expression (IHC 1+ or IHC 2+/ISH-) as determined by the central laboratory result. 3) Was never previously reported as HER2-positive (IHC 3+ or ISH+) as per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. 4) Is documented as HR+ (either estrogen receptor [ER] and/or progesterone receptor [PgR] positive [ER or PgR =1%]) per ASCO/CAP guidelines (Allison et al 2020).
- Must have an adequate tumor tissue sample available for assessment of HER2 by central laboratory, preferably in formalin fixation and paraffin embedding (FFPE) blocks based on a mandatory FFPE tumor sample obtained at the time of metastatic disease or later;
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Must have had either:
- Disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator, OR
- Disease progression on at least 2 previous lines of ET with or without a targeted therapy (such as CDK4/6, mammalian target of rapamycin [mTOR] or phosphoinositide 3-kinase [PI3-K] inhibitors) administered for the treatment of metastatic disease.
- No prior chemotherapy for advanced or metastatic breast cancer. Subjects who have received chemotherapy in the neo-adjuvant or adjuvant setting are eligible, as long as they have had a disease-free interval (defined as completion of systemic chemotherapy to diagnosis of advanced or metastatic disease) of >12 months.
- Life expectancy =12 weeks at screening.
- Subjects must have at least one measurable lesion as defined per RECIST v1.1 or have non-measurable, bone-only disease that can be assessed by computer tomography (CT) or Magnetic Resonance Imaging (MRI) or X-Ray. Lytic or mixed lytic bone lesions that can be assessed by CT or MRI or X-Ray in the absence of measurable disease as defined above is acceptable; subjects with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible.
- Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 7 months after the last dose of study treatment.
- Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening and throughout the duration of the study treatment and the washout period
Treatment Sites in Georgia
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