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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03505710
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : July 16, 2019
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Trastuzumab deruxtecan (DS-8201a) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 21, 2018
Estimated Primary Completion Date : August 25, 2020
Estimated Study Completion Date : August 25, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Cohort 1: HER2 OE
Cohort 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).
Drug: Trastuzumab deruxtecan (DS-8201a)
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Other Names:
  • DS-8201a
  • Experimental product

Experimental: Cohort 2: HER2 Mutated
Cohort 2 will enroll approximately 40 subjects with HER2-mutated, unresectable and/or metastatic NSCLC to receive trastuzumab deruxtecan (DS-8201a).
Drug: Trastuzumab deruxtecan (DS-8201a)
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Other Names:
  • DS-8201a
  • Experimental product

Primary Outcome Measures :
  1. Objective response rate (ORR) of trastuzumab deruxtecan (DS-8201a) assessed by independent central review (ICR) [ Time Frame: within 30 months ]
    ORR is assessed for each cohort by ICR, based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures :
  1. ORR of trastuzumab deruxtecan (DS-8201a) assessed by investigator [ Time Frame: within 30 months ]
    ORR is assessed for each cohort by the investigator

  2. Duration of Response (DoR) [ Time Frame: within 30 months ]
    Assessment categories: Investigator, ICR

  3. Progression-free Survival (PFS) [ Time Frame: within 30 months ]
    Assessment categories: Investigator, ICR

  4. 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) ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 tissue sample
  • For Cohort 2 only: Documented any known 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 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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03505710

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Contact: (for Asia Sites Only) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST)

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United States, California
University of California San Diego (UCSD) Recruiting
La Jolla, California, United States, 92093-1503
Contact: Principal Investigator    858-822-4171   
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Principal Investigator    720-848-5463    JOSE.M.PACHECO@UCDENVER.EDU   
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Principal Investigator    813-745-4673   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Principal Investigator    617-632-6036   
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Principal Investigator    734-647-6883   
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Principal Investigator    313-576-8753   
United States, Missouri
Washington University School of Medicine at St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Principal Investigator    314-747-1864   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065-6007
Contact: Principal Investigator    646-888-4201   
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Principal Investigator    206-288-7487   
Gustav Roussy Cancer Campus Grand Paris Recruiting
Villejuif, ile-de-France, France, 94805
Contact: Principal Investigator    +33 142114564   
Centre Leon Berard Recruiting
Lyon, Rhne, France, 69008
Contact: Principal Investigator    +33 426556761   
Hôpital Timone | AP HM Recruiting
Marseille, France, 13915
Contact: Principal Investigator    +33 491384644   
CHU Larrey Recruiting
Toulouse, France, 31059
Contact: Principal Investigator    +33 567771837   
Hôpital Larrey, CHU-Toulouse Recruiting
Toulouse, France, 31059
Contact: Principal Investigator    +33 567771837   
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan, 277-8577
Contact: See Central Contact         
Kindai University Hospital Recruiting
Ōsaka-sayama, Osaka, Japan, 589-8511
Contact: See Central Contact         
Shizuoka Cancer Center Recruiting
Nagaizumi, Sunto-gun, Japan, 411-8777
Contact: See Central Contact         
National Cancer Center Hospital Recruiting
Chuo Ku, Tokyo, Japan, 104-0045
Contact: See Central Contact         
Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Principal Investigator    +31 205122946   
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Contact: Principal Investigator    +34 932746077   
Hospital 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Principal Investigator    +34 913908000   
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Daiichi Sankyo Co., Ltd.
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Study Director: Global Team Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo, Inc. Identifier: NCT03505710     History of Changes
Other Study ID Numbers: DS8201-A-U204
2017-004781-94 ( EudraCT Number )
JapicCTI-183916 ( Registry Identifier: JAPIC )
First Posted: April 23, 2018    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address:
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
HER2 over-expression
HER2 mutation
Unresectable or metastatic

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs