Phase 2
Completed N=233
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]
Neoplasm, Gastrointestinal
Source: ClinicalTrials.gov NCT03329690 ↗
Enrolled (actual)
233
Serious AEs
36.5%
Results posted
Nov 2020
Primary outcomePrimary: Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) — 61; 7; 1; 8 Participants — p=<0.0001
Summary
The primary purpose of this trial is to compare the efficacy and safety of DS-8201a and physician's choice treatment in HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma patients who have progressed on two prior treatment regimens including fluoropyrimidine agent, platinum agent, and trastuzumab.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) |
61; 7; 1; 8; 61; 7 | <0.0001 sig |
| PRIMARY Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) |
11; 0; 0; 0; 10; 0 | — |
| SECONDARY Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) |
8.0; 7.1; 5.5; 7.0; 7.3; 8.4 | — |
| SECONDARY Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) |
5.6; 2.8; 4.9; 3.5; 4.4; 2.8 | — |
| SECONDARY Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set) |
8.4; 4.1; 3.9; 3.9; 6.8; 7.1 | — |
| SECONDARY Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) |
107; 34; 4; 38; 17; 15 | — |
| SECONDARY Objective Response Rate and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) |
5; 2; 5; 2; 0; 0 | — |
| SECONDARY Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set) |
4.2; 2.6; 2.9; 2.6; 3.7; 2.2 | — |
| SECONDARY Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set) |
60; 7; 1; 8; 10; 5 | — |
| SECONDARY Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a |
127; 119; 127; 137; 128; 123 | — |
| SECONDARY Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a |
12.1; 13.3; 13.3; 9.08; 7.62; 9.83 | — |
| SECONDARY Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a |
611; 572; 545; 667; 570; 547 | — |
| SECONDARY Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a |
46.7; 53.4; 44.5; 46.4; 44.9; 44.5 | — |
| SECONDARY Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a |
3.93; 3.90; 3.89; 4.00; 4.00; 4.00 | — |
| SECONDARY Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a |
5.77; 5.54; 5.52; 7.46; 6.40; 6.35 | — |
| SECONDARY Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set) |
125; 54; 7; 61; 20; 24 | — |
| SECONDARY Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) ≥20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set) |
125; 54; 7; 61; 20; 24 | — |
Eligibility Criteria
Inclusion Criteria
- Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction
- Progression on and after at least 2 prior regimens
- Has an adequate tumor sample
- Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Exclusion Criteria
- Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
- Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females
- Has a medical history of clinically significant lung disease
- Is suspected to have certain other protocol-defined diseases based on imaging at screening period
- Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
- safety or well-being of the participant or offspring
- safety of study staff
- analysis of results
Data sourced from ClinicalTrials.gov (NCT03329690). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.