Clinical Trials /

DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer

NCT03505710

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer
  • Official Title: A Phase 2, Multicenter, Open-Label, 2-Cohort Study of Trastuzumab Deruxtecan (DS-8201a), an Anti-HER2 Antibody Drug Conjugate (ADC), for HER2-Over-Expressing or -Mutated, Unresectable and/or Metastatic Non Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: DS8201-A-U204
  • SECONDARY ID: 2017-004781-94
  • NCT ID: NCT03505710

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Trastuzumab deruxtecan (DS-8201a)DS-8201a, Experimental productCohort 1: HER2 OE

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: HER2 OEExperimentalCohort 1 will enroll approximately 40 subjects with HER2-over-expressing (OE)(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma to receive trastuzumab deruxtecan (DS-8201a).
  • Trastuzumab deruxtecan (DS-8201a)
Cohort 2: HER2 MutatedExperimentalCohort 2 will enroll approximately 40 subjects with HER2-mutated, unresectable and/or metastatic NSCLC to receive trastuzumab deruxtecan (DS-8201a).
  • Trastuzumab deruxtecan (DS-8201a)

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 only: 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 sample

          -  For Cohort 2 only: Documented any known activating HER2 mutation from an archival
             tumor sample analyzed by CLIA laboratory or equivalent

          -  Presence of at least 1 measurable lesion assessed by the investigator based on
             Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

          -  Is willing and able to provide an adequate archival tumor 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:

          -  Was previously treated with HER2-targeted therapies, except for pan-HER class tyrosine
             kinase inhibitors

          -  For Cohort 1 only: 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) of trastuzumab deruxtecan (DS-8201a) assessed by independent central review (ICR)
Time Frame:within 30 months
Safety Issue:
Description:ORR is assessed for each cohort by ICR, based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures

Measure:ORR of trastuzumab deruxtecan (DS-8201a) assessed by investigator
Time Frame:within 30 months
Safety Issue:
Description:ORR is assessed for each cohort by the investigator
Measure:Duration of Response (DoR)
Time Frame:within 30 months
Safety Issue:
Description:Assessment categories: Investigator, ICR
Measure:Progression-free Survival (PFS)
Time Frame:within 30 months
Safety Issue:
Description:Assessment categories: Investigator, ICR
Measure:Overall Survival (OS)
Time Frame:until the end of the trial, including 40-day follow-up visit, followed by long-term follow-up visits until death, withdrawal of consent, loss to follow-up, or study closure, whichever occurs first (within approximately 30 months)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • HER2 over-expression
  • HER2 mutation
  • Unresectable or metastatic
  • Non-squamous
  • NSCLC

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