Home › Trials › NCT04379596

Investigating T-DXd combinations for advanced HER2-expressing gastric cancer

A Phase 1b/2 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Adult Participants With HER2-expressing Gastric Cancer (DESTINY-Gastric-03)

Phase 2 Interventional AstraZeneca · NCT04379596

This study is testing if a new drug called T-DXd, alone or with other treatments, can help people with advanced HER2-positive gastric and esophageal cancer feel better and fight their disease.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment450 (estimated)
Ages18 Years to 130 Years
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsCART, trastuzumab, chemotherapy, immunotherapy
Locations100 sites (Santa Monica, California and 99 other locations)
Trial IDNCT04379596 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or immunotherapy in patients with advanced HER2-expressing gastric and esophageal cancers. It aims to determine the tolerability, pharmacokinetics, and preliminary anti-tumor activity of these combinations. Participants will include those who have not received prior treatment for their advanced disease, and the study will assess the potential of T-DXd as a new therapeutic option for this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults with unresectable or metastatic HER2-positive or HER2-low adenocarcinoma of the stomach, gastroesophageal junction, or esophagus who have not received prior treatment.

Not a fit: Patients with early-stage gastric cancer or those who have previously received multiple treatments for their advanced disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced HER2-expressing gastric cancer.

How similar studies have performed: Other studies have shown promising results with similar approaches, indicating potential for success in this area.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion criteria:

1. Male and female participants must be at least 18 years of age. Other age restrictions may apply as per local regulations
2. Disease Characteristics:

   1. Locally advanced, unresectable, or metastatic disease based on most recent imaging
   2. For Part 1, 2, 3a, 4a pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results
   3. For Part 3b,4b and Part 5, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results
3. For Part 1, progression on or after at least one prior trastuzumabcontaining regimen For Part 2, Part 3, Part 4 and Part 5, previously untreated for unresectable or metastatic adenocarcinoma of the stomach/GEJ/ esophagus with with HER2-positive (Part 2 and Part 3 \[Arm 3A\] and 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 bone marrow and 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.

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.

Where this trial is running

Santa Monica, California and 99 other locations

+50 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Gastric CancerEsophageal CancerCarcinomaHER2TrastuzumabDeruxtecanT-DXdDS-8201a
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.