Clinical trial NCT03505710: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: HER2 over-expression
HER2 mutation
Unresectable or metastatic
Non-squamous
NSCLC
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Co., Ltd.
name: AstraZeneca
First posted: 2018-04-23
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: From screening, up to 36 months (data cut-off)
Secondary outcomes:
measure: 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)
timeFrame: From screening, up to 36 months (data cut-off)
measure: Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: From screening to documented tumor progression or death from any cause, up to 36 months (data cut-off)
measure: Progression-Free Survival (PFS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: From date of enrollment to first objective radiographic tumor progression or death from any cause,, up to 36 months (data cut-off)
measure: Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
timeFrame: From date of enrollment to death from any cause, up to 36 months (data cut-off)
measure: 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)
timeFrame: From first dose, up to 36 months (data cut-off)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine at St. Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: ile-de-France
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhne
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Toulouse
country: France
facility: CHU Larrey
city: Toulouse
country: France
facility: Hôpital Larrey, CHU-Toulouse
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Nagaizumi
country: Japan
facility: Shizuoka Cancer Center
state: Sunto-gun
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
Study officials:
affiliation: Daiichi Sankyo
name: Global Team Leader
role: STUDY_DIRECTOR
References:
citation: 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.