Study of T-DXd Monotherapy in Patients With HER2-expressing Locally Advanced or Metastatic Gastric or GEJ Adenocarcinoma Who Have Received 2 or More Prior Regimens

Phase 2

Completed

• Conditions: Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
• Interventions: Drug: Trastuzumab Deruxtecan

• Registration Number: NCT04989816
• Lead Sponsor: AstraZeneca

Brief Summary

This is a Phase II, open-label, single-arm, multicentre, study in China assessing the efficacy and safety of T-DXd in participants with HER2-expressing advanced gastric or GEJ adenocarcinoma who have received at least 2 prior regimens including a fluoropyrimidine agent and a platinum agent

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-14
• Study First Submitted QC: 2021-08-03
• Study First Posted: 2021-08-04
• Study Start: 2021-08-20
• Primary Completion: 2023-06-16
• Study Completion: 2024-02-28
• Results First Submitted: 2024-06-14
• Status Verified: 2024-11
• Results First Submitted QC: 2024-11-14
• Last Update Submitted: 2024-11-14
• Results First Posted: 2024-11-21
• Last Update Posted: 2024-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

Inclusion Criteria

1. Male or female ≥ 18 years of age
2. Pathologically documented gastric or GEJ adenocarcinoma
3. Disease progression on or after ≥ 2 prior platinum and fluoropyrimidine agents for advanced/metastatic disease
4. ECOG PS 0-1
5. Willing and able to provide an adequate newly-acquired tumour sample for confirmation of HER2 status
6. LVEF ≥ 50%

Exclusion Criteria

1. Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and CART. Drainage and CART.
2. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids
3. Active primary immunodeficiency, known HIV, active HBV, HCV infection.
4. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
5. History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening.
6. Lung-specific intercurrent clinically significant severe illnesses.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T-DXd arm	Trastuzumab Deruxtecan	T-DXd monotherapy

Primary Outcome Measures

Name	Time	Method
Confirmed Objective Response Rate by RECIST 1.1 Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Assessed up to a maximum of 19.3 months	Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by ICR per RECIST 1.1.
Best Objective Response Rate by RECIST 1.1 Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Assessed up to a maximum of 19.3 months	The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Assessed up to a maximum of 22 months	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 3 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 3 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 6 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 6 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 9 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 9 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 12 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 12 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 15 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 15 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 18 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 18 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Progression-free Survival (PFS) Rate at 21 Months Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Calculated at 21 months using the Kaplan-Meier technique	PFS based on ICR is defined as the time from date of enrolment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anti-cancer therapy prior to progression
Disease Control Rate (DCR) Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Assessed up to a maximum of 22 months	Disease control rate based on ICR according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR), partial response (PR) or stable disease (SD)
Disease Control Rate (DCR) Based on Independent Central Review (ICR) at Week 12	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. DCR assessed at Week 12	Disease control rate based on ICR according to RECIST version 1.1 was defined as the rate of best objective response of complete response (CR), partial response (PR) or stable disease (SD) for at least 11 weeks (ie 12 weeks - 1 week to allow for an early assessment within the assessment window)
Duration of Response (DoR) Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Assessed up to a maximum of 22 months	DoR defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) or death in the absence of progression based on investigator assessments by using RECIST version 1.1
Overall Survival (OS) Based on Independent Central Review (ICR)	From date of enrolment until death due to any cause. Assessed up to approximately 30 months (from date of first subject in to data cut-off 28February2024)	OS based on ICR is defined as the time from date of enrolment until the date of death due to any cause
Best Percentage Change in Sum of Diameters of Measurable Tumours Based on Independent Central Review (ICR)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. Assessed up to a maximum of 22 months	Best percentage change based on ICR is defined as the best change in target lesion tumour size from baseline (maximum reduction or minimum increase from baseline in the absence of a reduction)

Trial Locations

Locations (1)

Research Site; 🇨🇳 Zhengzhou, China