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

What this study is about

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 join (things the study team will check)

✅ You may be able to join if…

• Male and female participants must be at least 18 years of age. Other age restrictions may apply as per local regulations
• Disease Characteristics:
  • Locally advanced, unresectable, or metastatic disease based on most recent imaging
  • 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
  • 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
• 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
• Has measurable target disease assessed by the Investigator based on RECIST version 1.1
• Has protocol defined adequate bone marrow and organ function including cardiac, renal and hepatic function
• If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study.

🚫 You may not be able to join if…

• 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.
• Uncontrolled intercurrent illness.
• 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.
• Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
• Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
• Has spinal cord compression or clinically active central nervous system metastases.

Where this trial is running

• Research Site, Santa Monica, California, United States
• Research Site, Westwood, Kansas, United States
• Research Site, Baltimore, Maryland, United States
• Research Site, Boston, Massachusetts, United States
• Research Site, Boston, Massachusetts, United States
• Research Site, Ann Arbor, Michigan, United States
• Research Site, New York, New York, United States
• Research Site, Durham, North Carolina, United States
• Research Site, Houston, Texas, United States
• Research Site, Fairfax, Virginia, United States
• Research Site, Florianópolis, Brazil
• Research Site, Londrina, Brazil

+ 88 more sites.

Who to contact

AstraZeneca Clinical Study Information Center · 1-877-240-9479 · information.center@astrazeneca.com

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT04379596.