A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: DS-8201a
Intervention description: DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.
Intervention MeSH terms: Trastuzumab deruxtecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
Masking: None (Open Label)
Masking description: In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.
Enrollment: 253.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER-2 positive breast cancer; Metastatic or Unresectable; Resistant or refractory to T-DM1; DESTINY - Breast 01; Trastuzumab deruxtecan; T-DXd

Summary:

      Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond
      or become resistant to current treatment. DS-8201a is a new experimental product that is a
      combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may
      slow down tumor growth. This might improve outcomes for these patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men or women the age of majority in their country

          -  Has pathologically documented breast cancer that:

               1. is unresectable or metastatic

               2. has HER2 positive expression confirmed per protocol

          -  Has an adequate tumor sample

          -  Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors
             (RECIST) version 1.1

          -  Has protocol-defined adequate cardiac, renal and hepatic function

          -  Agrees to follow protocol-defined method(s) of contraception

        Exclusion Criteria:

          -  Has a medical history of myocardial infarction, symptomatic congestive heart failure
             (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia

          -  Has a corrected QT interval (QTc) prolongation to > 450 millisecond (ms) in males and
             > 470 ms in females

          -  Has a medical history of clinically significant lung disease

          -  Is suspected to have certain other protocol-defined diseases based on imaging at
             screening period

          -  Has history of any disease, metastatic condition, drug/medication use or other
             condition that might, per protocol or in the opinion of the investigator, compromise:

               1. safety or well-being of the participant or offspring

               2. safety of study staff

               3. analysis of results