DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer (DESTINY-Lung01)

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) (DESTINY-Lung01)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Marseille, France, 12915
    • Hôpital Nord - CHU Marseille
  • Toulouse, France, 31059
    • CHU Larrey
  • Toulouse, France, 31059
    • Hôpital Larrey, CHU-Toulouse
  • Rhne
    • Lyon, Rhne, France, 69008
      • Centre Leon Berard
  • ile-de-France
    • Villejuif, ile-de-France, France, 94805
      • Institut Gustave Roussy
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Osaka
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
  • Sunto-gun
    • Nagaizumi, Sunto-gun, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Netherlands Cancer Institute
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
• United States
  • California
    • La Jolla, California, United States, 92093-1503
      • University of California San Diego (UCSD)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine at St. Louis
  • New York
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: HER2 Overexpressing; Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).	Drug: Trastuzumab deruxtecan; Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.; Other Names: DS-8201a; Experimental product
Experimental: Cohort 1a: HER2 Overexpressing; Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).	Drug: Trastuzumab deruxtecan; Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.; Other Names: DS-8201a; Experimental product
Experimental: Cohort 2: HER2 Mutated; Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).	Drug: Trastuzumab deruxtecan; Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.; Other Names: DS-8201a; Experimental product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)	The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported.	Up to 36 months (data cut-off)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)	The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on investigator assessment is reported.	Up to 36 months (data cut-off)
Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)	Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on independent central review and investigator assessment is reported.	Up to 36 months (data cut-off)
Progression-Free Survival (PFS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)	Progression-free survival (PFS) was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. PFS based on independent central review and investigator assessment is reported.	Up to 36 months (data cut-off)
Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)	Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.	Up to 36 months (data cut-off)
Percentage of Participants With Disease Control Rate (DCR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)	Disease Control Rate (DCR) was defined as the percentage of participants who achieved a best overall response of CR, PR, or stable disease (SD) during study treatment. Confirmation of CR/PR was required. DCR based on independent central review and investigator assessment is reported.	Up to 36 months (data cut-off)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: AstraZeneca; Daiichi Sankyo Co., Ltd.
• Investigators: Study Director: Global Team Leader, Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazieres J, Nagasaka M, Bazhenova L, Saltos AN, Felip E, Pacheco JM, Perol M, Paz-Ares L, Saxena K, Shiga R, Cheng Y, Acharyya S, Vitazka P, Shahidi J, Planchard D, Janne PA; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251. doi: 10.1056/NEJMoa2112431. Epub 2021 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): May 3, 2021
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Non-squamous; HER2 mutation; Unresectable or metastatic; HER2 over-expression
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: DS8201-A-U204; 2017-004781-94 (EudraCT Number); JapicCTI-183916 (Registry Identifier: JAPIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. 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: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No