Gastric CancerPhase 2DG-03NCT04379596
Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)
A Phase 2 study testing Fluorouracil (5-FU), Capecitabine and Durvalumab in people with Gastric Cancer, run by AstraZeneca at 71 sites in 14 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Gastric Cancer
- What is being tested?
- Fluorouracil (5-FU), Capecitabine and Durvalumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 452 participants
- Where
- 71 sitesin 14 countries
- Study dates
- 3 Jun 2020to 4 May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
71 sites in 14 countries.
71 sites in 14 countries
Russia10 sites
Research Site
Kostroma, 156005
Research Site
Moscow, 115478
Research Site
Moscow, 125284
Research Site
Moscow, 143423
Research Site
Moscow, 143442
Research Site
Novosibirsk, 630099
Research Site
Saint Petersburg, 195271
Research Site
Saint Petersburg, 196603
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197758
China7 sites
Research Site
Chengdu, 610042
Research Site
Guangzhou, 510062
Research Site
Hefei, 230001
Research Site
Shanghai, 200032
Research Site
Shenyang, 110001
Research Site
Wuhan, 430000
Research Site
Zhengzhou, 450008
Germany6 sites
Research Site
Frankfurt, 60488
Research Site
Frankfurt, 60590
Research Site
Hamburg, 20249
Research Site
Leipzig, 04103
Research Site
Mannheim, 68167
Research Site
München, 81675
Italy6 sites
Research Site
Milan, 20133
Research Site
Milan, 20162
Research Site
Naples, 80131
Research Site
Padova, 35128
Research Site
Roma, 00168
Research Site
Verona, 37134
Brazil5 sites
Research Site
Londrina, 86015-520
Research Site
Ribeirão Preto, 14051-140
Research Site
Santa Maria, 97015-450
Research Site
São Jose Do Rio Preto, 15090-000
Research Site
São Paulo, 045202-001
Poland5 sites
Research Site
Gdansk, 80-214
Research Site
Konin, 62-500
Research Site
Koszalin, 75-581
Research Site
Krakow, 31-501
Research Site
Warsaw, 02-034
South Korea5 sites
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Spain5 sites
Research Site
Barcelona, 08035
Research Site
Madrid, 28007
Research Site
Madrid, 28034
Research Site
Santander, 39008
Research Site
Seville, 41013
Taiwan5 sites
Research Site
Kaohsiung City, 80756
Research Site
Tainan, 704
Research Site
Taipei, 10002
Research Site
Taipei, 11217
Research Site
Taoyuan, 333
United Kingdom5 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Dundee, DD1 9SY
Research Site
London, NW1 2PG
Research Site
Manchester, M20 4BX
Research Site
Sutton, SM2 5PT
United States4 sites
Research Site
Baltimore, Maryland, 21287
Research Site
Boston, Massachusetts, 02215
Research Site
Houston, Texas, 77090
Research Site
New York, New York, 10065
Canada3 sites
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Québec, Quebec, G1J 1Z4
Research Site
Toronto, Ontario, M5G 2M9
Netherlands3 sites
Research Site
Amsterdam, 1066CX
Research Site
Amsterdam, 1081 HV
Research Site
Utrecht, 3584CG
About this study
Official 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)
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
- Being tested
- Fluorouracil (5-FU), Capecitabine, Durvalumab, Oxaliplatin, Trastuzumab
- Keywords
- Gastric Cancer, Esophageal Cancer, Carcinoma, HER2, Trastuzumab, Deruxtecan, T-DXd, DS-8201a, Gastroesophageal Cancer, Adenocarcinoma
- Medical subject headings
- Stomach Neoplasms, Esophageal Neoplasms, Carcinoma, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluorouracil (5-FU)Drug
5-FU: administered as an IV infusion
CapecitabineDrug
Capecitabine: administered orally
DurvalumabBiological
Also called MEDI4736
Durvalumab: administered as an IV infusion
OxaliplatinDrug
Oxaliplatin: administered as an IV infusion
TrastuzumabBiological
Trastuzumab: administered as an IV infusion
Trastuzumab deruxtecanDrug
Also called DS-8201a, Enhertu
T-DXd: administered as an IV infusion
CisplatinDrug
Cisplatin: administered as an IV infusion
PembrolizumabBiological
Pembrolizumab: administered as an IV infusion
VolrustomigBiological
Also called MEDI5752
Volrustomig: administered as an IV infusion
RilvegostomigBiological
Also called AZD2936
Rilvegostomig: administered as an IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Arm 1A | Experimental | T-DXd and 5-fluorouracil (5-FU) Receives: Drug: Fluorouracil (5-FU); Drug: Trastuzumab deruxtecan |
| Arm 1B | Experimental | T-DXd and capecitabine Receives: Drug: Capecitabine; Drug: Trastuzumab deruxtecan |
| Arm 1C | Experimental | T-DXd and durvalumab Receives: Biological: Durvalumab; Drug: Trastuzumab deruxtecan |
| Arm 1D(b) | Experimental | T-DXd, capecitabine, and oxaliplatin Receives: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Trastuzumab deruxtecan |
| Arm 1E(a) | Experimental | T-DXd, 5-FU, and durvalumab Receives: Drug: Fluorouracil (5-FU); Biological: Durvalumab; Drug: Trastuzumab deruxtecan |
| Arm 1E(b) | Experimental | T-DXd, capecitabine, and durvalumab Receives: Drug: Capecitabine; Biological: Durvalumab; Drug: Trastuzumab deruxtecan |
| Arm 2A | Active comparator | Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Oxaliplatin; Biological: Trastuzumab; Drug: Cisplatin |
| Arm 2B | Experimental | T-DXd monotherapy Receives: Drug: Trastuzumab deruxtecan |
| Arm 2C | Experimental | T-DXd, 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan |
| Arm 2D | Experimental | T-DXd, pembrolizumab and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Pembrolizumab |
| Arm 2E | Experimental | T-DXd and pembrolizumab Receives: Drug: Trastuzumab deruxtecan; Biological: Pembrolizumab |
| Arm 2F | Experimental | T-DXd, pembrolizumab and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Pembrolizumab |
| Arm 3A | Experimental | T-DXd, Volrustomig and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig |
| Arm 3B | Experimental | T-DXd, Volrustomig and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig |
| Arm 4A | Experimental | T-DXd, Rilvegostomig and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Rilvegostomig |
| Arm 4B | Experimental | T-DXd, Rilvegostomig and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Rilvegostomig |
| Part 5 Main Cohort | Experimental | T-DXd, Volrustomig and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig |
| Part 5 Cohort 2 | Experimental | T-DXd, Volrustomig and 5-FU or capecitabine Receives: Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Measured: Safety will be assessed up to the follow-up period, approximately 24 months.
Part 1: Ocurrence of dose-limiting toxicities (DLTs)
Occurrence of dose limiting toxicities
Measured: Safety will be assessed up to the follow-up period, approximately 24 months.
Part 1: Changes from baseline in laboratory parameters
Changes in laboratory parameters (every in appropriate units) compared to baseline results.
Measured: Safety will be assessed up to the follow-up period, approximately 24 months.
Part 1: Changes from baseline in vital signs
Changes in vital signs results compared to baseline results.
Measured: Safety will be assessed up to the follow-up period, approximately 24 months.
Part 1: Changes from baseline in electrocardiogram (ECG) results
Changes in ECG results compared to baseline results.
Measured: Safety will be assessed up to the follow-up period, approximately 24 months.
Part 2, Part 3, Part 4 and Part 5: Endpoint assessed by Investigator per RECIST v1.1: Confirmed Objective Response Rate (ORR)
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.
Measured: (Endpoint: ORR) Efficacy will be assessed at an average of approximately 12 months
Secondary outcomes (19)
Part 1: Objective Response Rate (ORR)
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.
Measured: Efficacy will be assessed at an average of approximately 12 months
Part 2, Part 3, Part 4 and Part 5: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Measured: Safety will be assessed up to follow-up period, approximately 24 months
Part 2, Part 3, Part 4 and Part 5: Changes from baseline in laboratory parameters
Changes in laboratory parameters (every in appropriate units) compared to baseline results.
Measured: Safety will be assessed up to follow-up period, approximately 24 months
Part 2, Part 3, Part 4 and Part 5: Changes from baseline in vital signs
Changes in vital signs results compared to baseline results.
Measured: Safety will be assessed up to follow-up period, approximately 24 months
Part 2, Part 3 , Part 4 and Part 5: Changes from baseline in body weight
Changes in body weight in kilograms compared to baseline results.
Measured: Safety will be assessed up to follow-up period, approximately 24 months
Part 2, Part 3, Part 4 and Part 5: Changes from baseline in electrocardiogram (ECG) results
Changes in ECG results compared to baseline results.
Measured: Safety will be assessed up to follow-up period, approximately 24 months
Duration of Response (DoR)
DOR is defined as the time from the date of first documented response until the date of documented progression or death
Measured: Until progression or death, efficacy (DoR) will be assessed up to approximately 24 months
Disease Control Rate (DCR)
DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD)
Measured: Efficacy will be assessed at an average of approximately 12 months
Progression Free Survival (PFS)
PFS is the time from date of first dose until the date of objective disease progression or death
Measured: Until progression or death, efficacy (PFS) will be assessed up to approximately 24 months
Overall survival (OS)
OS is the time from date of first dose until death due to any cause
Measured: Until death, efficacy (OS) will be assessed up to approximately 24 months
Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms
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
Measured: While on study drug up to study completion, approximately 24 months
Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab
Individual participant data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab.
Measured: While on study drug up to study completion, approximately 24 months
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)
Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd and durvalumab.
Measured: While on study drug up to study completion, approximately 24 months
Serum concentrations of volrustomig and rilvegostomig in study arms including T-DXd in combination with volrustomig and T-DXd in combination with rilvegostomig
Individual participant data and descriptive statistics will be provided for data at each time point for rilvegostomig and volrustomig
Measured: While on study drug up to study completion, approximately 24 months
Comparison of ORR
Comparison of objective response rate between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results
Measured: While on study drug up to study completion, approximately 24 months
Comparison of DCR
Comparison of disease control rate between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results
Measured: While on study drug up to study completion, approximately 24 months
Comparison of DoR
Comparison of duration of response between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results
Measured: While on study drug up to study completion, approximately 24 months
Comparison of PFS
Comparison of progression-free survival between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results
Measured: While on study drug up to study completion, approximately 24 months
Comparison of OS
Comparison of overall survival between participants using local HER2 test results and central HER2 test results from tumor samples with evaluable results
Measured: While on study drug up to study completion, approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2020
- Study start3 Jun 2020
- Primary completion4 May 2027 (estimated)
- Study completion4 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will consist of 2 phases: a dose escalation phase (Part 1) and dose expansion phases (Part 2, Part 3, Part 4 and Part 5). Part 1 will enroll HER2-overexpressing (IHC 3+ or IHC 2+/ISH+), previously treated gastric, gastro-esophageal junction (GEJ) or esophageal cancer patients, and Part 2 will enroll HER2-overexpressing patients who have not received prior treatment for metastatic or unresectable disease. Part 3, Part 4 and Part 5 will enroll HER2-expressing patients who have not received prior treatment for metastatic or unresectable disease. In addition to safety and tolerability, this study will also assess ORR, DoR, DCR, OS, PFS and other measures of antitumor activity among treatment groups. Tumor evaluation using RECIST v1.1 will be conducted at screening and every 6 weeks until RECIST 1.1 objective disease progression or withdrawal of consent.
- Masking
- None (open label)
- Enrolment
- 452 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04379596
- Sponsor's protocol ID
- D967LC00001
- Other IDs
- 2019-004483-22, 2019
- Acronym
- DG-03
- Status last verified
- Aug 2026
- First submitted
- 5 May 2020
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.
PubMed 40341124
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT04379596
- Acronym / sponsor ID
- DG-03 / D967LC00001
- Conditions
- Gastric Cancer
- Keywords
- Gastric Cancer, Esophageal Cancer, Carcinoma, HER2, Trastuzumab, Deruxtecan, T-DXd, DS-8201a
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 452 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 3 Jun 2020 (actual)
- Primary completion
- 4 May 2027 (estimated)
- Study completion
- 4 May 2027 (estimated)
- First posted
- 7 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 18
- Model description
- The study will consist of 2 phases: a dose escalation phase (Part 1) and dose expansion phases (Part 2, Part 3, Part 4 and Part 5). Part 1 will enroll HER2-overexpressing (IHC 3+ or IHC 2+/ISH+), previously treated gastric, gastro-esophageal junction (GEJ) or esophageal cancer patients, and Part 2 will enroll HER2-overexpressing patients who have not received prior treatment for metastatic or unresectable disease. Part 3, Part 4 and Part 5 will enroll HER2-expressing patients who have not received prior treatment for metastatic or unresectable disease. In addition to safety and tolerability, this study will also assess ORR, DoR, DCR, OS, PFS and other measures of antitumor activity among treatment groups. Tumor evaluation using RECIST v1.1 will be conducted at screening and every 6 weeks until RECIST 1.1 objective disease progression or withdrawal of consent.
| Arm | Type | Receives |
|---|---|---|
| Arm 1A | Experimental | Drug: Fluorouracil (5-FU), Drug: Trastuzumab deruxtecanT-DXd and 5-fluorouracil (5-FU) |
| Arm 1B | Experimental | Drug: Capecitabine, Drug: Trastuzumab deruxtecanT-DXd and capecitabine |
| Arm 1C | Experimental | Biological: Durvalumab, Drug: Trastuzumab deruxtecanT-DXd and durvalumab |
| Arm 1D(b) | Experimental | Drug: Capecitabine, Drug: Oxaliplatin, Drug: Trastuzumab deruxtecanT-DXd, capecitabine, and oxaliplatin |
| Arm 1E(a) | Experimental | Drug: Fluorouracil (5-FU), Biological: Durvalumab, Drug: Trastuzumab deruxtecanT-DXd, 5-FU, and durvalumab |
| Arm 1E(b) | Experimental | Drug: Capecitabine, Biological: Durvalumab, Drug: Trastuzumab deruxtecanT-DXd, capecitabine, and durvalumab |
| Arm 2A | Active comparator | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Oxaliplatin, Biological: Trastuzumab, Drug: CisplatinTrastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin |
| Arm 2B | Experimental | Drug: Trastuzumab deruxtecanT-DXd monotherapy |
| Arm 2C | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecanT-DXd, 5-FU or capecitabine |
| Arm 2D | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: PembrolizumabT-DXd, pembrolizumab and 5-FU or capecitabine |
| Arm 2E | Experimental | Drug: Trastuzumab deruxtecan, Biological: PembrolizumabT-DXd and pembrolizumab |
| Arm 2F | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: PembrolizumabT-DXd, pembrolizumab and 5-FU or capecitabine |
| Arm 3A | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: VolrustomigT-DXd, Volrustomig and 5-FU or capecitabine |
| Arm 3B | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: VolrustomigT-DXd, Volrustomig and 5-FU or capecitabine |
| Arm 4A | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: RilvegostomigT-DXd, Rilvegostomig and 5-FU or capecitabine |
| Arm 4B | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: RilvegostomigT-DXd, Rilvegostomig and 5-FU or capecitabine |
| Part 5 Main Cohort | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: VolrustomigT-DXd, Volrustomig and 5-FU or capecitabine |
| Part 5 Cohort 2 | Experimental | Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Trastuzumab deruxtecan, Biological: VolrustomigT-DXd, Volrustomig and 5-FU or capecitabine |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female participants must be at least 18 years of age. Other age restrictions may apply as per local regulations
- Disease Characteristics:
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fluorouracil (5-FU)5-FU: administered as an IV infusion | Drug | Arm 1A, Arm 1E(a), Arm 2A, Arm 2C, Arm 2D, Arm 2F, Arm 3A, Arm 3B, Arm 4A, Arm 4B, Part 5 Cohort 2, Part 5 Main Cohort |
| CapecitabineCapecitabine: administered orally | Drug | Arm 1B, Arm 1D(b), Arm 1E(b), Arm 2A, Arm 2C, Arm 2D, Arm 2F, Arm 3A, Arm 3B, Arm 4A, Arm 4B, Part 5 Cohort 2, Part 5 Main Cohort |
| DurvalumabAlso: MEDI4736Durvalumab: administered as an IV infusion | Biological | Arm 1C, Arm 1E(a), Arm 1E(b) |
| OxaliplatinOxaliplatin: administered as an IV infusion | Drug | Arm 1D(b), Arm 2A |
| TrastuzumabTrastuzumab: administered as an IV infusion | Biological | Arm 2A |
| Trastuzumab deruxtecanAlso: DS-8201a, EnhertuT-DXd: administered as an IV infusion | Drug | Arm 1A, Arm 1B, Arm 1C, Arm 1D(b), Arm 1E(a), Arm 1E(b), Arm 2B, Arm 2C, Arm 2D, Arm 2E, Arm 2F, Arm 3A, Arm 3B, Arm 4A, Arm 4B, Part 5 Cohort 2, Part 5 Main Cohort |
| CisplatinCisplatin: administered as an IV infusion | Drug | Arm 2A |
| PembrolizumabPembrolizumab: administered as an IV infusion | Biological | Arm 2D, Arm 2E, Arm 2F |
| VolrustomigAlso: MEDI5752Volrustomig: administered as an IV infusion | Biological | Arm 3A, Arm 3B, Part 5 Cohort 2, Part 5 Main Cohort |
| RilvegostomigAlso: AZD2936Rilvegostomig: administered as an IV infusion | Biological | Arm 4A, Arm 4B |
Primary outcome
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
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
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.
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.
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.
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.
19 secondary outcomes
Part 1: Objective Response Rate (ORR)
Time frame: Efficacy will be assessed at an average of approximately 12 months
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
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
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
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
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
Duration of Response (DoR)
Time frame: Until progression or death, efficacy (DoR) will be assessed up to approximately 24 months
Disease Control Rate (DCR)
Time frame: Efficacy will be assessed at an average of approximately 12 months
Progression Free Survival (PFS)
Time frame: Until progression or death, efficacy (PFS) will be assessed up to approximately 24 months
Overall survival (OS)
Time frame: Until death, efficacy (OS) will be assessed up to approximately 24 months
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
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
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
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
Comparison of ORR
Time frame: While on study drug up to study completion, approximately 24 months
Comparison of DCR
Time frame: While on study drug up to study completion, approximately 24 months
Comparison of DoR
Time frame: While on study drug up to study completion, approximately 24 months
Comparison of PFS
Time frame: While on study drug up to study completion, approximately 24 months
Comparison of OS
Time frame: While on study drug up to study completion, approximately 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Derived from this study: PubMed 40341124Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
71 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fluorouracil (5-FU), Capecitabine and Durvalumab in people with Gastric Cancer, run by AstraZeneca at 71 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in Russia, China, Germany, Italy, Brazil and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04379596, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.