Prospective, multi-center, randomized, open label comparative Phase III study in patients with intermediate to high-risk (as defined in the SURVIVE trial) HER2-positive or HER2-low early breast cancer, who participate in the SURVIVE trial and experience a molecular relapse, as assessed based on a positive circulating tumor DNA (ctDNA) result, with 2:1 allocation to:
* Arm A: Trastuzumab-Deruxtecan (i.v. 5,4 mg/kg, q3w) + endocrine therapy (if hormonal-receptor-positive) for 16 cycles or until relapse, if earlier * Arm B: Continuous treatment of physician's choice (may include endocrine treatment, CDK4/6-Inhibition, T-DM1, Olaparib, Trastuzumab, Pertuzumab, Capecitabine or Neratinib)
Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
Females or males, ≥ 18 years and ≤ 75 years of age.
HER2-positive defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) in Her2 2+ tumors (as defined in 2018 American Society of Clinical Oncology - College of American Pathologists [ASCO-CAP] guidelines)
HER2-low defined as an immunohistochemistry (IHC) score of 1+ or an IHC score of 2+ with a mandatory negative in situ hybridization (ISH), as defined in 2018 American Society of Clinical Oncology - College of American Pathologists [ASCO-CAP] guidelines.
Stage IV (metastatic) breast cancer.
ipsi- or contralateral non-invasive carcinoma of the breast (DCIS)
other, curatively treated in-situ disease
adequately treated non-melanoma carcinoma of the skin
Parallel
Trastuzumab-Deruxtecan
DrugTrastuzumab-Deruxtecan (i.v. 5,4 mg/kg, q3w) + endocrine therapy (if hormonal-receptor-positive) for 16 cycles or until relapse, if earlier
Physicians Choice (PhC).
Other interventionContinuous treatment of physician's choice (may include endocrine treatment, CDK4/6-Inhibition, T-DM1, Olaparib, Trastuzumab, Pertuzumab, Capecitabine or Neratinib)
ctDNA clearance rate 12 months after randomization
To compare ctDNA clearance rate twelve months after randomization between patients in the experimental arm (Arm A) versus patients in the standard of care arm (Arm B). ctDNA is measured as per RaDaR assay (see 5.8). Endpoint: ctDNA clearance rate is defined as the proportion of patients with a ctDNA negative blood test result at a given time point: (Patients with negative cfDNA at 12 months)/(all patients)
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Prof. Wolfgang Janni
Lead sponsor
University of Ulm
Sponsor institution
