Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)

NCT04644237 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: DS8201-A-U2062020-003427-42
• Study Type: interventional
• Target: 152
• Locations: 10 countries
• Sites: 50

Brief Summary

This study was designed to evaluate the safety and efficacy of trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer (NSCLC) participants who had disease recurrence or progression during/after at least one regimen of prior anticancer therapy (second line or later) that must have contained a platinum-based chemotherapy drug.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-small Cell Lung Cancer; Trastuzumab Deruxtecan

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer

  Confirmed objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR), was assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (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.

  9 months after the last participant is randomized to data cut off, up to approximately 21 months

Secondary Outcomes (12)

• Percentage of Participants With Confirmed Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung CancerTumors

  9 months after the last participant is randomized or later to data cut off, up to approximately 35 months

• Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer

  9 months after the last participant is randomized or later to data cut off, up to approximately 35 months

• Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer

  9 months after the last participant is randomized or later to data cut off, up to approximately 35 months

• Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer

  9 months after the last participant is randomized or later to data cut off, up to approximately 35 months

• Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors

  9 months after the last participant is randomized or later to data cut off, up to approximately 35 months

Study Arms (2)

Trastuzumab deruxtecan 6.4 mg/kg

EXPERIMENTAL

Participants will be randomized to receive trastuzumab deruxtecan 6.4 mg/kg administered by intravenous infusion every 3 weeks (Q3W).

Drug: Trastuzumab deruxtecan

Trastuzumab deruxtecan 5.4 mg/kg

EXPERIMENTAL

Participants will be randomized to receive trastuzumab deruxtecan 5.4 mg/kg administered by intravenous infusion every 3 weeks (Q3W).

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

Trastuzumab deruxtecan 100 mg will be provided as a sterile lyophilized powder and reconstituted with 5 mL water for injection (final concentration 20 mg/mL \[ie, 100 mg/5 mL\]). The study drug will be administered as an intravenous (IV) infusion over 30 to 90 min Q3W ± 2 days. The initial dose of study drug will be infused for 90 ± 10 min.

Trastuzumab deruxtecan 5.4 mg/kg; Trastuzumab deruxtecan 6.4 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Men or women ≥18 years, follow local regulatory requirements if the legal age of the consent for study participation is \>18 years
• Pathologically documented metastatic NSCLC with a known activating HER2 mutation. Note: A HER2 mutation documented only from a liquid biopsy samples cannot be used for enrollment.
• Had previous treatment including platinum therapy in the metastatic/locally advanced setting and not amenable to curative surgery or radiation. Participant must have progressed during or after the last treatment regimen or discontinued because of unacceptable toxicity.
• Presence of at least 1 measurable lesion confirmed by the blinded Independent Central Review based on RECIST version 1.1
• Willing and able to provide an archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Resection and core needle biopsy are acceptable. Fine needle aspirates or cell block are not acceptable.
• Eastern Cooperative Oncology Group performance status 0 to 1
• Left ventricular ejection fraction ≥ 50% within 28 days before randomization Resection and core needle biopsy are acceptable - Adequate organ function as specified in protocol within 14 days before randomization
• Adequate treatment washout period before randomization
• Participants of reproductive/childbearing potential agree to use a highly effective form of contraception (or avoid intercourse) during study period and up to 7 months (females) and 4 months (males) after last study dose
• Males should not freeze or donate sperm throughout the study period up to at least 4 months after last study dose; females should not donate or retrieve ova for their own use throughout the study period and up to at least 7 months after last study dose
• Life expectancy 3 months or more

You may not qualify if:

• Known driver mutation in the epidermal growth factor receptor (EGFR), BRAF, or MET exon 14 gene or a known anaplastic lymphoma kinase (ALK), ROS1, RET, or NTRK fusion
• Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above upper limit of normal at screening (as defined by the manufacturer) and without any myocardial infarction (MI)-related symptoms should have a cardiologic consultation before randomization to rule out MI
• Corrected QT interval (QTcF) prolongation \> 470 msec (females) or \>450 msec (males) based on average of the triplicate12-lead electrocardiogram at screening
• History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
• Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
• History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
• History of severe hypersensitivity reactions to other monoclonal antibodies
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results
• Known human immunodeficiency virus (HIV) infection
• Known active, clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C) such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1
• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline
• Pregnant, breastfeeding, or planning to become pregnant
• Otherwise considered inappropriate for the study by the Investigator

Sponsors & Collaborators

• Daiichi Sankyo: lead
• AstraZeneca: collaborator

Study Sites (50)

University of Colorado Denver - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Massachusetts General Hospital (MGH) - Hematology/Oncology

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Cancer Institute/Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Michigan

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Virgina Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

St John of God Subiaco Hospital

Subiaco, 6008, Australia

Location

Princess Alexandra Hospital

Woolloongabba, 4102, Australia

Location

University Health Network

Toronto, M5G0A3, Canada

Location

Centre Leon Berard

Lyon, 69008, France

Location

Assistance Publique Hopitaux de Marseille AP-HM, Hopital NORD

Marseille, 13015, France

Location

Hopital Pontchaillou

Rennes, 35000, France

Location

CHU Nantes

Saint-Herblain, 44800, France

Location

CHU toulouse - hôpital Larrey

Toulouse, 31059, France

Location

Gustav Roussy

Villejuif, 94800, France

Location

Ospedale San Luca

Lucca, 55100, Italy

Location

IRCCS Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

SC Oncologia, AOU Policlinico Modena

Modena, 41124, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Strutturadi Oncologia

Napoli, 80131, Italy

Location

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Humanitas Cancer Center Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Aichi Cancer Center Hospital

Chikusa, 464-8681, Japan

Location

National Cancer Central Hospital

Chūōku, 104-0045, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 11111, Japan

Location

National Cancer Center Hospital East

Kashiwa, 277-0882, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Kindai University Hospital

Ōsaka-sayama, 589-8511, Japan

Location

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Chungbuk National University Hospital

Jungbuk, 28644, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 3080, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08023, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Clinica Univ. de Navarra - P

Pamplona, 31008, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Chung Shan Medical University Hospital

Taichung, 40705, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Chang Gung Memorial Hospital CGMH - LinKou Branch

Taoyuan District, 333, Taiwan

Location

Related Publications (2)

• Janne PA, Goto Y, Kubo T, Ninomiya K, Kim SW, Planchard D, Ahn MJ, Smit E, Johannes de Langen A, Perol M, Pons-Tostivint E, Novello S, Hayashi H, Shimizu J, Kim DW, Pereira K, Cheng FC, Taguchi A, Cheng Y, Dunton K, Ali A, Goto K. Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC. J Thorac Oncol. 2025 Dec;20(12):1814-1828. doi: 10.1016/j.jtho.2025.07.129. Epub 2025 Jul 30.

  PMID: 40749900 DERIVED

• Goto K, Goto Y, Kubo T, Ninomiya K, Kim SW, Planchard D, Ahn MJ, Smit EF, de Langen AJ, Perol M, Pons-Tostivint E, Novello S, Hayashi H, Shimizu J, Kim DW, Kuo CH, Yang JC, Pereira K, Cheng FC, Taguchi A, Cheng Y, Feng W, Tsuchihashi Z, Janne PA. Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial. J Clin Oncol. 2023 Nov 1;41(31):4852-4863. doi: 10.1200/JCO.23.01361. Epub 2023 Sep 11.

  PMID: 37694347 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sanyko, Inc

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: November 25, 2020
• Study Start: March 19, 2021
• Primary Completion: December 23, 2022
• Study Completion: August 23, 2024
• Last Updated: November 21, 2025
• Results First Posted: January 30, 2024

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

CA (1); ES (6); NL (2); US (11); FR (6); IT (6); TW (5); AU (2); KR (5); JP (6)