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

Phase 2

Completed

• Conditions: HER2-mutant Non-Small Cell Lung Cancer
• Interventions: Drug: Trastuzumab deruxtecan

• Registration Number: NCT05246514
• Lead Sponsor: AstraZeneca

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-11
• Study First Submitted QC: 2022-02-11
• Study First Posted: 2022-02-18
• Study Start: 2022-07-13
• Primary Completion: 2023-09-23
• Results First Submitted: 2024-09-04
• Status Verified: 2024-11
• Study Completion: 2024-11-04
• Results First Submitted QC: 2024-11-27
• Last Update Submitted: 2024-11-27
• Results First Posted: 2024-12-04
• Last Update Posted: 2024-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T-DXd arm	Trastuzumab deruxtecan	Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle.

Primary Outcome Measures

Name	Time	Method
ICR-assessed ORR (Objective Response Rate)	At an average of approximately 14 months	Confirmed ORR, defined as the percentage of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.

Secondary Outcome Measures

Name	Time	Method
Investigator-assessed ORR (Objective Response Rate)	An average of approximately 14 months	Confirmed ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1
ICR-assessed and Investigator-assessed DoR (Duration of Response)	At an average of approximately 14 months	DoR is time from the initial confirmed response (CR or PR) until documented tumour progression or death from any cause.
ICR-assessed and Investigator-assessed DCR (Disease Control Rate)	Approximately 6 weeks	DCR is the percentage of participants who achieved confirmed CR, PR, or SD during study intervention.
ICR-assessed and Investigator-assessed PFS (Progression-free Survival)	An average of approximately 14 months	PFS is the time from date of enrolment until first objective radiographic tumour progression or death from any cause.
OS (Overall Survival)	An average of approximately 22 months	OS is the time from date of enrolment until death from any cause.
ICR-assessed CNS-PFS (Central Nervous System Progression-free Survival)	An average of approximately 14 months	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.
Serum Concentrations of T-DXd	An average of approximately 14 months	Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd.
Serum Concentrations of Total Anti-HER2 Antibody	An average of approximately 14 months	Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for total anti-HER2 antibody.
Serum Concentrations of DXd	An average of approximately 14 months	Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for DXd.

Trial Locations

Locations (1)

Research Site; 🇨🇳 Zhengzhou City, China