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

NCT ID: NCT03505710

Last Updated: 2025-05-30

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

181 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-21

Study Completion Date

2024-04-17

Brief Summary

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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

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Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

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).

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Cohort 2: HER2 Mutated

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Interventions

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Trastuzumab deruxtecan

Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Intervention Type DRUG

Other Intervention Names

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DS-8201a Experimental product

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo Co., Ltd.

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Team Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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University of California San Diego (UCSD)

La Jolla, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Washington University School of Medicine at St. Louis

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Centre Leon Berard

Lyon, Rhne, France

Site Status

Hôpital Nord - CHU Marseille

Marseille, , France

Site Status

CHU Larrey

Toulouse, , France

Site Status

Hôpital Larrey, CHU-Toulouse

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

Kindai University Hospital

Ōsaka-sayama, Osaka, Japan

Site Status

Shizuoka Cancer Center

Nakatogari, Sunto-gun, Japan

Site Status

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan

Site Status

Netherlands Cancer Institute

Amsterdam, , Netherlands

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital 12 de Octubre

Madrid, , Spain

Site Status

Countries

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United States France Japan Netherlands Spain

References

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Smit EF. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer: a plain language summary of the DESTINY-Lung01 study. Future Oncol. 2024;20(27):1961-1971. doi: 10.1080/14796694.2024.2355724. Epub 2024 Jul 16.

Reference Type DERIVED
PMID: 39012221 (View on PubMed)

Smit EF, Felip E, Uprety D, Nagasaka M, Nakagawa K, Paz-Ares Rodriguez L, Pacheco JM, Li BT, Planchard D, Baik C, Goto Y, Murakami H, Saltos A, Pereira K, Taguchi A, Cheng Y, Yan Q, Feng W, Tsuchihashi Z, Janne PA. Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial. Lancet Oncol. 2024 Apr;25(4):439-454. doi: 10.1016/S1470-2045(24)00064-0.

Reference Type DERIVED
PMID: 38547891 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34534430 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-004781-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

JapicCTI-183916

Identifier Type: REGISTRY

Identifier Source: secondary_id

DS8201-A-U204

Identifier Type: -

Identifier Source: org_study_id

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