For Healthcare Professionals

Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)


About the study

DESTINY-Gastric03 will investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or immunotherapy in HER2-expressing advanced/metastatic gastric/gastroesophageal junction (GEJ) and esophageal adenocarcinoma patients. Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or immunotherapy administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and preliminary anti-tumor efficacy so as to permit further clinical testing. T-DXd in combination with cytotoxic chemotherapy or immune checkpoint inhibitor administered to HER2-expressing gastric, GEJ and esophageal cancer patients who have not received prior treatment for advanced/metastatic disease will show preliminary evidence of anti-tumour activity and the potential to become a therapeutic option for this patient population.

Who can take part

You may be eligible to participate in the study if you meet the following criteria:


Inclusion criteria:

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

Disease Characteristics:

  1. Locally advanced, unresectable, or metastatic disease based on most recent imaging
  2. For Part 1, 2, 3a, 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, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results
  4. For Part 1, progression on or after at least one prior trastuzumabcontaining regimen For Part 2 and Part 3, previously untreated for unresectable or metastatic adenocarcinoma of the stomach/GEJ/ esophagus with with HER2-positive (Part 2 and Part 3, Arm 3A) or HER2-low (Part 3, Arm 3B) status
  5. Has measurable target disease assessed by the Investigator based on RECIST version 1.1
  6. Has protocol defined adequate organ function including cardiac, renal and hepatic function
  7. 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. History of active primary immunodeficiency, known HIV, active 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.
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Study Locations

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How to Apply

Contact the study center to learn if this study is a good match for you.

Study’s details


Gastric Cancer

Age (in years)

18 - 130


Phase 2

Participants needed


Est. Completion Date

Sep 29, 2025

Treatment type



AstraZeneca identifier


Study number


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