Skip to main content
OpenTrials
Recruiting

NCT Number: NCT04379596

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Gastric Cancer Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Stomach Diseases Stomach Neoplasms

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Florianópolis, Brazil

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Fluorouracil (5-FU)

Drug

5-FU: administered as an IV infusion

Capecitabine

Drug

Capecitabine: administered orally

Durvalumab

Biological

Durvalumab: administered as an IV infusion

Other names: MEDI4736

Oxaliplatin

Drug

Oxaliplatin: administered as an IV infusion

trastuzumab

Biological

Trastuzumab: administered as an IV infusion

Trastuzumab Deruxtecan

Drug

T-DXd: administered as an IV infusion

Other names: DS-8201a, Enhertu

Cisplatin

Drug

Cisplatin: administered as an IV infusion

Pembrolizumab

Biological

Pembrolizumab: administered as an IV infusion

Volrustomig

Biological

Volrustomig: administered as an IV infusion

Other names: MEDI5752

Rilvegostomig

Biological

Rilvegostomig: administered as an IV infusion

Other names: AZD2936

Primary outcomes

  1. Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0

    Time frame: Safety will be assessed up to the follow-up period, approximately 24 months.

    Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

  2. Part 1: Ocurrence of dose-limiting toxicities (DLTs)

    Time frame: Safety will be assessed up to the follow-up period, approximately 24 months.

    Occurrence of dose limiting toxicities

  3. Part 1: Changes from baseline in laboratory parameters

    Time frame: Safety will be assessed up to the follow-up period, approximately 24 months.

    Changes in laboratory parameters (every in appropriate units) compared to baseline results.

  4. Part 1: Changes from baseline in vital signs

    Time frame: Safety will be assessed up to the follow-up period, approximately 24 months.

    Changes in vital signs results compared to baseline results.

  5. Part 1: Changes from baseline in electrocardiogram (ECG) results

    Time frame: Safety will be assessed up to the follow-up period, approximately 24 months.

    Changes in ECG results compared to baseline results.

  6. Part 2, Part 3, Part 4 and Part 5: Endpoint assessed by Investigator per RECIST v1.1: Confirmed Objective Response Rate (ORR)

    Time frame: (Endpoint: ORR) Efficacy will be assessed at an average of approximately 12 months

    Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Secondary outcomes

  1. Part 1: Objective Response Rate (ORR)

    Time frame: Efficacy will be assessed at an average of approximately 12 months

    Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

  2. Part 2, Part 3, Part 4 and Part 5: Occurrence of adverse events (AEs) and serious adverse events (SAEs)

    Time frame: Safety will be assessed up to follow-up period, approximately 24 months

    Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

  3. Part 2, Part 3, Part 4 and Part 5: Changes from baseline in laboratory parameters

    Time frame: Safety will be assessed up to follow-up period, approximately 24 months

    Changes in laboratory parameters (every in appropriate units) compared to baseline results.

  4. Part 2, Part 3, Part 4 and Part 5: Changes from baseline in vital signs

    Time frame: Safety will be assessed up to follow-up period, approximately 24 months

    Changes in vital signs results compared to baseline results.

  5. Part 2, Part 3 , Part 4 and Part 5: Changes from baseline in body weight

    Time frame: Safety will be assessed up to follow-up period, approximately 24 months

    Changes in body weight in kilograms compared to baseline results.

  6. Part 2, Part 3, Part 4 and Part 5: Changes from baseline in electrocardiogram (ECG) results

    Time frame: Safety will be assessed up to follow-up period, approximately 24 months

    Changes in ECG results compared to baseline results.

  7. Duration of Response (DoR)

    Time frame: Until progression or death, efficacy (DoR) will be assessed up to approximately 24 months

    DOR is defined as the time from the date of first documented response until the date of documented progression or death

  8. Disease Control Rate (DCR)

    Time frame: Efficacy will be assessed at an average of approximately 12 months

    DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD)

  9. Progression Free Survival (PFS)

    Time frame: Until progression or death, efficacy (PFS) will be assessed up to approximately 24 months

    PFS is the time from date of first dose until the date of objective disease progression or death

  10. Overall survival (OS)

    Time frame: Until death, efficacy (OS) will be assessed up to approximately 24 months

    OS is the time from date of first dose until death due to any cause

  11. Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms

    Time frame: While on study drug up to study completion, approximately 24 months

    Individual participant data and descriptive statistics will be provided for serum concentration data at each time point for each dose level for T-DXd, total anti-HER2 antibody, MAAA-1181a

  12. Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab

    Time frame: While on study drug up to study completion, approximately 24 months

    Individual participant data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab.

  13. Presence of ADAs for T-DXD, durvalumab, volrustomig and rilvegostomig (in study arms including T-DXd and durvalumab, and T-DXd and volrustomig, and T-DXd and rilvegostomig respectively)

    Time frame: While on study drug up to study completion, approximately 24 months

    Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd and durvalumab.

  14. Serum concentrations of volrustomig and rilvegostomig in study arms including T-DXd in combination with volrustomig and T-DXd in combination with rilvegostomig

    Time frame: While on study drug up to study completion, approximately 24 months

    Individual participant data and descriptive statistics will be provided for data at each time point for rilvegostomig and volrustomig

  15. Comparison of ORR

    Time frame: While on study drug up to study completion, approximately 24 months

    Comparison of objective response rate between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results

  16. Comparison of DCR

    Time frame: While on study drug up to study completion, approximately 24 months

    Comparison of disease control rate between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results

  17. Comparison of DoR

    Time frame: While on study drug up to study completion, approximately 24 months

    Comparison of duration of response between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results

  18. Comparison of PFS

    Time frame: While on study drug up to study completion, approximately 24 months

    Comparison of progression-free survival between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results

  19. Comparison of OS

    Time frame: While on study drug up to study completion, approximately 24 months

    Comparison of overall survival between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results

Study contacts

Contact information is provided by the study sponsor or research team.

AstraZeneca Clinical Study Information Center

CONTACT

[email protected]

1-877-240-9479

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Daiichi Sankyo

Registry information

Official study title

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)

Acronym: DG-03

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
May 7, 2020
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.