DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Trastuzumab deruxtecan
Intervention description: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Intervention MeSH terms: Trastuzumab; Trastuzumab deruxtecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 181.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2 over-expression; HER2 mutation; Unresectable or metastatic; Non-squamous; NSCLC

Summary:

      The primary objective of this trial is to evaluate the efficacy of trastuzumab deruxtecan in
      HER2-overexpressing and/or HER2-mutated advanced NSCLC participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥20 years old in Japan, ≥18 years old in other countries

          -  Pathologically documented unresectable and/or metastatic non-squamous NSCLC

          -  Has relapsed from or is refractory to standard treatment or for which no standard
             treatment is available

          -  For Cohort 1 and Cohort 1a: HER2-overexpression (IHC 2+ or 3+) status must be assessed
             and confirmed by Clinical Laboratory Improvement Amendments (CLIA)-certified
             laboratory or equivalent, from an archival tumor tissue sample

          -  For Cohort 2 only: Participant has any known documented activating HER2 mutation from
             an archival tumor tissue sample analyzed by CLIA laboratory or equivalent. Note: HER2
             mutation documented only from a liquid biopsy sample cannot be used for enrollment.

          -  Presence of at least 1 measurable lesion assessed by the investigator and based on
             Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

          -  Is willing and able to provide an adequate archival tumor tissue sample

          -  Is willing to undergo a tissue biopsy, after the completion of the most recent
             treatment regimen

          -  Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

        Exclusion Criteria:

          -  Had been previously treated with HER2-targeted therapies, except for pan-HER class
             tyrosine kinase inhibitors

          -  For Cohort 1 and Cohort 1a: Has known HER2 mutation

          -  Has a medical history of myocardial infarction, symptomatic congestive heart failure
             (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia

          -  Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that
             required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis that
             cannot be ruled out due to imaging at screening

          -  Has a QT interval corrected by Fridericia's formula (QTcF) 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