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

Description

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.

Conditions

Gastric Cancer

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Study Overview

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Study Details

Study overview

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.

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)

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

Condition
Gastric Cancer
Intervention / Treatment

-

Contacts and Locations

Santa Monica

Research Site, Santa Monica, California, United States, 90404

Westwood

Research Site, Westwood, Kansas, United States, 66205

Baltimore

Research Site, Baltimore, Maryland, United States, 21287

Boston

Research Site, Boston, Massachusetts, United States, 02114

Boston

Research Site, Boston, Massachusetts, United States, 02215

Ann Arbor

Research Site, Ann Arbor, Michigan, United States, 48109

New York

Research Site, New York, New York, United States, 10065

Durham

Research Site, Durham, North Carolina, United States, 27710

Houston

Research Site, Houston, Texas, United States, 77090

Fairfax

Research Site, Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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 and 4b, 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 and Part 4, 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 \[Arm 3B\] and Part 4 \[Arm 4B\])) 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.
  • 1. History of active primary immunodeficiency, known HIV, active chronic, or past hepatitis B infection, or hepatitis C 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.

Ages Eligible for Study

18 Years to 130 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

AstraZeneca,

Study Record Dates

2026-07-30