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

Study Overview
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Brief Summary
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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

Official Title
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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)

Conditions
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Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Intervention / Treatment
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* Drug: Trastuzumab Deruxtecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age Pathologically documented gastric or GEJ adenocarcinoma Disease progression on or after ≥ 2 prior platinum and fluoropyrimidine agents for advanced/metastatic disease ECOG PS 0-1 Willing and able to provide an adequate newly-acquired tumour sample for confirmation of HER2 status LVEF ≥ 50% Exclusion Criteria: Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and CART. Drainage and CART. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids Active primary immunodeficiency, known HIV, active HBV, HCV infection. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening. Lung-specific intercurrent clinically significant severe illnesses.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single group assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T-DXd arm<br>T-DXd monotherapy | Drug: Trastuzumab Deruxtecan<br>* Trastuzumab deruxtecan (T-DXd) by intravenous infusion<br>* Other names: DS8201a; AZD4552; T-DXd;|

What is the study measuring?
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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. | An average of approximately 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| investigator-assessed ORR | 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 | 
| PFS | PFS is defined as time from date of enrolment until progression per RECIST 1.1 as assessed by ICR or death due to any cause. PFS will be evaluated based on ICR and on investigator assessment. | An average of approximately 14 months | 
| DCR | DCR is defined as the percentage of participants who have a confirmed CR/PR or SD(without subsequent anticancer therapy) after date of enrolment.DCR will be evaluated based on ICR and on investigator assessment. | Approximately 6 weeks | 
| DoR | DoR is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. DoR will be evaluated based on ICR and on investigator assessment. | An average of approximately 14 months | 
| OS | OS is defined as time from date of enrolment until the date of death due to any cause | At least 16 months | 
| Tumour size change | Tumour size change will be evaluated based on ICR and investigator assessment. | An average of approximately 14 months | 
| 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 | 
| Serum concentration 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. | 
| Serum concentration of MAAA-1181a. | Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for MAAA-1181a. | An average of approximately 14 months. | 
| Immunogenicity | Presence of ADAs against T-DXd in serum during treatment (before infusion on Day 1 of Cycles 1, 2, and 4, and every 4 cycles thereafter) and at follow-up. Neutralising ADAs will also be assessed | An average of approximately 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, HER2, Trastuzumab, Deruxtecan, T-DXd, DS-8201a, ERBB2