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

• ClinicalTrials.gov Identifier: NCT03505710
• Recruitment Status: Active, not recruiting
• First Posted: April 23, 2018
• Results First Posted: May 17, 2022
• Last Update Posted: May 15, 2023
• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Daiichi Sankyo Co., Ltd.; AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Tracking Information

• First Submitted Date: April 13, 2018
• First Posted Date: April 23, 2018
• Results First Submitted Date: April 25, 2022
• Results First Posted Date: May 17, 2022
• Last Update Posted Date: May 15, 2023
• Actual Study Start Date: May 21, 2018
• Actual Primary Completion Date: May 3, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2022)

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) [ Time Frame: Up to 36 months (data cut-off) ]

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.

Original Primary Outcome Measures (submitted: April 13, 2018)

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

Current Secondary Outcome Measures (submitted: April 25, 2022)

• 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) [ Time Frame: Up to 36 months (data cut-off) ]
  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.
• Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC) [ Time Frame: Up to 36 months (data cut-off) ]
  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.
• Progression-Free Survival (PFS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC) [ Time Frame: Up to 36 months (data cut-off) ]
  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.
• Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC) [ Time Frame: Up to 36 months (data cut-off) ]
  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.
• 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) [ Time Frame: Up to 36 months (data cut-off) ]
  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.

Original Secondary Outcome Measures (submitted: April 13, 2018)

• ORR of trastuzumab deruxtecan (DS-8201a) assessed by investigator [ Time Frame: within 30 months ]
  ORR is assessed for each cohort by the investigator
• Duration of Response (DoR) [ Time Frame: within 30 months ]
  Assessment categories: Investigator, ICR
• Progression-free Survival (PFS) [ Time Frame: within 30 months ]
  Assessment categories: Investigator, ICR
• 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) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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) (DESTINY-Lung01)
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

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

Study Arms

• 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).
  Intervention: Drug: Trastuzumab deruxtecan
• 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).
  Intervention: Drug: Trastuzumab deruxtecan
• Experimental: Cohort 2: HER2 Mutated
  Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).
  Intervention: Drug: Trastuzumab deruxtecan

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 25, 2022): 181
• Original Estimated Enrollment (submitted: April 13, 2018): 80
• Estimated Study Completion Date: March 31, 2024
• Actual Primary Completion Date: May 3, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Japan, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT03505710
• Other Study ID Numbers: DS8201-A-U204; 2017-004781-94 ( EudraCT Number ); JapicCTI-183916 ( Registry Identifier: JAPIC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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 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/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

• Current Responsible Party: Daiichi Sankyo, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Daiichi Sankyo, Inc.
• Original Study Sponsor: Same as current

Collaborators

• Daiichi Sankyo Co., Ltd.
• AstraZeneca

Investigators

• Study Director: Global Team Leader; Daiichi Sankyo, Inc.

• PRS Account: Daiichi Sankyo, Inc.
• Verification Date: May 2023