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

Non-Small Cell Lung Cancer Clinical Trial

— DESTINY-Lung01  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03505710
• Other study ID #: DS8201-A-U204
• Secondary ID: 2017-004781-94Ja
• Status: Completed
• Phase: Phase 2
• Start date: May 21, 2018
• Est. completion date: April 17, 2024

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: April 17, 2024
• Est. primary completion date: May 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• 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.

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon	Rhne
France	Hôpital Nord - CHU Marseille	Marseille
France	CHU Larrey	Toulouse
France	Hôpital Larrey, CHU-Toulouse	Toulouse
France	Institut Gustave Roussy	Villejuif	ile-de-France
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Shizuoka Cancer Center	Nagaizumi	Sunto-gun
Japan	Kindai University Hospital	Osaka-sayama	Osaka
Netherlands	Netherlands Cancer Institute	Amsterdam
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital 12 de Octubre	Madrid
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Hospital	Aurora	Colorado
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University of California San Diego (UCSD)	La Jolla	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University School of Medicine at St. Louis	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca, Daiichi Sankyo Co., Ltd.

Countries where clinical trial is conducted

United States,  France,  Japan,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)