Clinical trial NCT05246514: A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC
Official title: An Open-label, Single-arm, Phase 2 Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for Patients With HER2-mutant Metastatic NSCLC Who Have Disease Progression on or After at Least One-line of Treatment (DESTINY-Lung05)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2-mutant Non-Small Cell Lung Cancer
Keywords: DL05
T-DXd
HER2-mutant Non-Small Cell Lung Cancer
NSCLC
Trastuzumab deruxtecan
ERBB2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2022-02-18
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of T-DXd in participants with HER2 mutant metastatic non-squamous NSCLC.


Eligibility criteria: Inclusion Criteria:

* Pathologically documented metastatic non-squamous NSCLC.
* Has relapsed from or is refractory to at least one-line of anticancer treatment.
* Documented HER2 exon 19 or 20 mutation from central FFPE tumour tissue testing.
* WHO or ECOG performance status of 0 or 1.
* Presence of at least one measurable lesion assessed by the investigator based on RECIST 1.1.
* LVEF ≥ 50% within 28 days before enrolment.

Exclusion Criteria:

* Mixed small cell lung cancer, squamous histology NSCLC, and sarcomatoid histology variant NSCLC.
* Corrected QT interval (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males), based on average of the screening triplicate 12-lead ECG.
* History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (excluding alopecia) not yet resolved to Grade ≤1 or baseline. Participants with clinically stable chronic Grade 2 toxicity not reasonably expected to be exacerbated by study intervention may be included only after consultation with the AstraZeneca study physician or designee.
* Has been previously treated with HER2-targeted therapies, except for pan-HER class TKIs or has received prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.

Primary outcomes:
measure: ICR-assessed ORR (Objective Response Rate)
timeFrame: At an average of approximately 14 months
Secondary outcomes:
measure: Investigator-assessed ORR (Objective Response Rate)
timeFrame: An average of approximately 14 months
measure: ICR-assessed and Investigator-assessed DoR (Duration of Response)
timeFrame: At an average of approximately 14 months
measure: ICR-assessed and Investigator-assessed DCR (Disease Control Rate)
timeFrame: Approximately 6 weeks
measure: ICR-assessed and Investigator-assessed PFS (Progression-free Survival)
timeFrame: An average of approximately 14 months
measure: OS (Overall Survival)
timeFrame: An average of approximately 22 months
measure: ICR-assessed CNS-PFS (Central Nervous System Progression-free Survival)
timeFrame: An average of approximately 14 months
measure: Serum Concentrations of T-DXd
timeFrame: An average of approximately 14 months
measure: Serum Concentrations of Total Anti-HER2 Antibody
timeFrame: An average of approximately 14 months
measure: Serum Concentrations of DXd
timeFrame: An average of approximately 14 months
Other outcomes:
Locations:
city: Baoding
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: ShenZhen
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Zhengzhou City
country: China
facility: Research Site
Study officials:
References: