A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

HER2-mutant Non-Small Cell Lung Cancer Clinical Trial

— DL-05  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05246514
• Other study ID #: D7811C00001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 13, 2022
• Est. completion date: June 24, 2024

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: June 24, 2024
• Est. primary completion date: September 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• HER2-mutant Non-Small Cell Lung Cancer

Intervention

Drug:
• Trastuzumab deruxtecan
administered as an IV infusion

Locations

Country	Name	City	State
China	Research Site	Baoding
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Linyi
China	Research Site	Nanjing
China	Research Site	Shandong
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	ShenZhen
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xiamen
China	Research Site	Yangzhou
China	Research Site	Zhengzhou City

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICR-assessed ORR (objective response rate)	Confirmed ORR, defined as the proportion of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.	At an average of approximately 14 months
Secondary	Investigator-assessed ORR (objective response rate)	Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1	An average of approximately 14 months
Secondary	ICR-assessed and investigator-assessed DoR (duration of response)	DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.	At an average of approximately 14 months
Secondary	ICR-assessed and investigator-assessed DCR (disease control rate)	DCR is the proportion of participants who achieved confirmed CR, PR, or SD during study intervention.	Approximately 6 weeks
Secondary	ICR-assessed and investigator-assessed PFS (progression-free survival)	PFS is the time from date of enrolment until first objective radiographic tumour progression or death from any cause.	An average of approximately 14 months
Secondary	OS (overall survival)	OS is the time from date of enrolment until death from any cause.	An average of approximately 22 months
Secondary	ICR-assessed CNS-PFS (central nervous system progression-free survival)	CNS-PFS is the time from date of enrolment until CNS tumour progression per RECIST 1.1 as assessed by ICR due to any cause in the absence of CNS progression.	An average of approximately 14 months
Secondary	Serum concentrations of T-DXd	Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.	An average of approximately 14 months
Secondary	Serum concentrations of total anti-HER2 antibody	Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.	An average of approximately 14 months
Secondary	Serum concentrations of DXd	Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for DXd.	An average of approximately 14 months
Secondary	Immunogenicity	Presence of ADAs against T-DXd in serum during treatment and at follow-up.	An average of approximately 14 months
Secondary	Frequency of AEs, SAEs and AESIs	Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.	An average of approximately 16 months