adenocarcinoma of the stomach, GEJ, or esophagus
Conditions
Interventions
Experimental: Arm 1A: T-DXd and 5-fluorouracil (5-FU)
Drug: Fluorouracil (5-FU)/ 5-FU: administered as an IV infusion
Drug: Trastuzumab deruxtecan/ T-DXd: administered as an IV infusion/ Other Name: D
Sponsors
Inoguchi Akihiro
AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants must be at least 18 years of age (20 years of age in Japan) 2. Disease Characteristics: Locally advanced, unresectable, or metastatic disease based on most recent imaging. For Part 1, 2, 3a and 4a pathologically documented adenocarcinoma of the stomach, GEJ, or esophagus, HER2-positive (IHC 3+ or IHC 2+/ISH-positive) based on existing local tissue testing results. For Part 3b,4b and 5, pathologically documented adenocarcinoma of the stomach, GEJ, or esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on existing local tissue testing results. 3. For Part 1, progression on or after at least one prior trastuzumab-containing regimen. previously untreated for unresectable or metastatic adenocarcinoma of the stomach, GEJ, or esophagus, with HER2-positive (Part 2 and Part 3, Arm 3A, Part 4, Arm 4A) or HER2-low (Part 3, Arm 3B, Part 4 Arm 4B and part 5) status. 4. Has measurable target disease assessed by the Investigator based on RECIST version 1.1. 5. Has protocol- defined adequate organ function including cardiac, renal and hepatic function . 6. If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months (female) or 6 months (male) after last dose of study drug.
Exclusion criteria
Exclusion criteria: 1. Part 1 to 4: History of active primary immunodeficiency, known HIV, active chronic, or past hepatitis B infection, or hepatitis C infection. Part 5: evidence of active, uncontroled HIV, HBV or HCV infection. 2. Uncontrolled intercurrent illness. 3. History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening. 4. Lung-specific intercurrent clinically significant severe illnesses. 5. Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals. 6. Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). 7. Has spinal cord compression or clinically active central nervous system metastases.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: To assess safety and tolerability, and to determine the recommended Phase 2 dose (RP2D) or the highest protocol-defined dose of T-DXd combinations with capecitabine, 5-fluorouracil, oxaliplatin, or durvalumab Occurrence of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and changes from baseline in laboratory parameters, vital signs, and electrocardiogram (ECG) results Part 2, Part 3, Part 4 and Part 5: To assess the antitumor activity of T-DXd combinations at the RP2D Endpoint assessed by Investigator per RECIST v1.1: - Confirmed Objective Response Rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: To assess the antitumor activity of T-DXd combinations Endpoints assessed by Investigator per RECIST v1.1: - Confirmed ORR - Disease control rate (DCR) - Duration of response (DoR) - Progression-free survival (PFS) - Overall survival (OS) Part 2, Part 3, Part 4 and Part 5: To assess the antitumor activity of T-DXd combinations Endpoints assessed by Investigator per RECIST v1.1: - Disease control rate (DCR) - Duration of response (DoR) - Progression-free survival (PFS) - Overall survival (OS) Part 2, Part 3, Part 4 and Part 5: To assess the safety and tolerability of T-DXd monotherapy and T-DXd combination regimens Occurrence of adverse events (AEs), serious adverse events (SAEs), and changes from baseline in laboratory parameters, vital signs, body weight, and electrocardiogram(ECG) results | — |
Countries
Brazil, Canada, China, Germany, Italy, Japan, Korea, Netherlands, Poland, Russia, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactContact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
Outcome results
None listed