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

NCT03505710 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: DS8201-A-U2042017-004781-94JapicCTI-183916
• Study Type: interventional
• Target: 181
• Locations: 5 countries
• Sites: 21

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

HER2 over-expression; HER2 mutation; Unresectable or metastatic; Non-squamous; NSCLC

Outcome Measures

Primary Outcomes (1)

• 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.

  From screening, up to 36 months (data cut-off)

Secondary Outcomes (5)

• 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)

  From screening, 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)

  From screening to documented tumor progression or death from any cause, 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)

  From date of enrollment to first objective radiographic tumor progression or death from any cause,, 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)

  From date of enrollment to death from 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)

  From first dose, up to 36 months (data cut-off)

Study Arms (3)

Cohort 1: HER2 Overexpressing

EXPERIMENTAL

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

Cohort 1a: HER2 Overexpressing

EXPERIMENTAL

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

Cohort 2: HER2 Mutated

EXPERIMENTAL

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

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

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

Also known as: DS-8201a, Experimental product

Cohort 1: HER2 Overexpressing; Cohort 1a: HER2 Overexpressing; Cohort 2: HER2 Mutated

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:
• safety or well-being of the participant or offspring
• safety of study staff
• analysis of results

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Daiichi Sankyo Co., Ltd.: collaborator
• AstraZeneca: collaborator

Study Sites (21)

University of California San Diego (UCSD)

La Jolla, California, 92093, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine at St. Louis

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Centre Leon Berard

Lyon, Rhne, 69008, France

Location

Hôpital Nord - CHU Marseille

Marseille, 12915, France

Location

CHU Larrey

Toulouse, 31059, France

Location

Hôpital Larrey, CHU-Toulouse

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Kindai University Hospital

Ōsaka-sayama, Osaka, 589-8511, Japan

Location

Shizuoka Cancer Center

Nakatogari, Sunto-gun, 411-8777, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Related Publications (3)

• 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.

  PMID: 39012221 DERIVED

• 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.

  PMID: 38547891 DERIVED

• 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.

  PMID: 34534430 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo_us@daiichisankyo.com

908-992-6400

Study Officials

• Global Team Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 23, 2018
• Study Start: May 21, 2018
• Primary Completion: May 3, 2021
• Study Completion: April 17, 2024
• Last Updated: May 30, 2025
• Results First Posted: May 17, 2022

Record last verified: 2025-05

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

JP (4); US (9); ES (2); FR (5); NL (1)