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 (DG-06)

A Single-arm Study of Trastuzumab Deruxtecan (T-DXd) Monotherapy for Patients With HER2-expressing Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma Who Have Received 2 or More Prior Regimens (DESTINY-Gastric06)

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

Study Overview

• Status: Completed
• Conditions: Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
• Intervention / Treatment: Drug: Trastuzumab Deruxtecan

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100191
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Chengdu, China, 610042
    • Research Site
  • Fuzhou, China, 350014
    • Research Site
  • Guangzhou, China, 510062
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310009
    • Research Site
  • Hangzhou, China, 310020
    • Research Site
  • Hefei, China, 230031
    • Research Site
  • Hefei, China, 230001
    • Research Site
  • Jinan, China, 250001
    • Research Site
  • Lanzhou, China, 730030
    • Research Site
  • Nan Chong, China, 637000
    • Research Site
  • Nanchang, China, 330029
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shenyang, China, 110001
    • Research Site
  • Suzhou, China, 215006
    • Research Site
  • Wuhan, China, 430000
    • Research Site
  • Xiamen, China, 361003
    • Research Site
  • Yinchuan, China, 750004
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
  • Zhengzhou City, China, 450000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-DXd arm; T-DXd monotherapy	Drug: Trastuzumab Deruxtecan; Trastuzumab deruxtecan (T-DXd) by intravenous infusion; Other Names: DS8201a; AZD4552; T-DXd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate by RECIST 1.1 Based on Independent Central Review (ICR)	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.	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
Best Objective Response Rate by RECIST 1.1 Based on Independent Central Review (ICR)	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	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 3 Months Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 6 Months Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 9 Months Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 12 Months Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 15 Months Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 18 Months Based on Independent Central Review (ICR)	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	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
Progression-free Survival (PFS) Rate at 21 Months Based on Independent Central Review (ICR)	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	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
Disease Control Rate (DCR) Based on Independent Central Review (ICR)	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)	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 (DCR) Based on Independent Central Review (ICR) 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)	Tumour assessments every 6 weeks from 1st dose of treatment until Recist 1.1 defined radiological progressive disease. DCR assessed at Week 12
Duration of Response (DoR) Based on Independent Central Review (ICR)	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	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
Overall Survival (OS) Based on Independent Central Review (ICR)	OS based on ICR is defined as the time from date of enrolment until the date of death due to any cause	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)
Best Percentage Change in Sum of Diameters of Measurable Tumours Based on Independent Central Review (ICR)	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)	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events (AEs) and serious adverse events (SAEs)	Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0	On average of approximately 16 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo Co., Ltd.

Publications and helpful links

Helpful Links

• CSP redacted
• SAP redacted
• CSR Synopsis redacted

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: HER2; Gastric Cancer; Trastuzumab; DS-8201a; T-DXd; Deruxtecan; Gastroesophageal Junction Adenocarcinoma; ERBB2
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: D9676C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . A Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No