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

NCT ID: NCT04379596

Last Updated: 2025-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

413 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-03

Study Completion Date

2027-06-01

Brief Summary

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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.

Detailed Description

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Conditions

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Gastric Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1A

T-DXd and 5-fluorouracil (5-FU)

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 1B

T-DXd and capecitabine

Group Type EXPERIMENTAL

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 1C

T-DXd and durvalumab

Group Type EXPERIMENTAL

Durvalumab

Intervention Type BIOLOGICAL

Durvalumab: administered as an IV infusion

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 1D(b)

T-DXd, capecitabine, and oxaliplatin

Group Type EXPERIMENTAL

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Oxaliplatin

Intervention Type DRUG

Oxaliplatin: administered as an IV infusion

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 1E(a)

T-DXd, 5-FU, and durvalumab

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Durvalumab

Intervention Type BIOLOGICAL

Durvalumab: administered as an IV infusion

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 1E(b)

T-DXd, capecitabine, and durvalumab

Group Type EXPERIMENTAL

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Durvalumab

Intervention Type BIOLOGICAL

Durvalumab: administered as an IV infusion

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 2A

Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin

Group Type ACTIVE_COMPARATOR

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Oxaliplatin

Intervention Type DRUG

Oxaliplatin: administered as an IV infusion

Trastuzumab

Intervention Type BIOLOGICAL

Trastuzumab: administered as an IV infusion

Cisplatin

Intervention Type DRUG

Cisplatin: administered as an IV infusion

Arm 2B

T-DXd monotherapy

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 2C

T-DXd, 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Arm 2D

T-DXd, pembrolizumab and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab: administered as an IV infusion

Arm 2E

T-DXd and pembrolizumab

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab: administered as an IV infusion

Arm 2F

T-DXd, pembrolizumab and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab: administered as an IV infusion

Arm 3A

T-DXd, Volrustomig and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Volrustomig

Intervention Type BIOLOGICAL

Volrustomig: administered as an IV infusion

Arm 3B

T-DXd, Volrustomig and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Volrustomig

Intervention Type BIOLOGICAL

Volrustomig: administered as an IV infusion

Arm 4A

T-DXd, Rilvegostomig and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Rilvegostomig

Intervention Type BIOLOGICAL

Rilvegostomig: administered as an IV infusion

Arm 4B

T-DXd, Rilvegostomig and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Rilvegostomig

Intervention Type BIOLOGICAL

Rilvegostomig: administered as an IV infusion

Part 5 Main Cohort

T-DXd, Volrustomig and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Volrustomig

Intervention Type BIOLOGICAL

Volrustomig: administered as an IV infusion

Part 5 Cohort 2

T-DXd, Volrustomig and 5-FU or capecitabine

Group Type EXPERIMENTAL

Fluorouracil (5-FU)

Intervention Type DRUG

5-FU: administered as an IV infusion

Capecitabine

Intervention Type DRUG

Capecitabine: administered orally

Trastuzumab deruxtecan

Intervention Type DRUG

T-DXd: administered as an IV infusion

Volrustomig

Intervention Type BIOLOGICAL

Volrustomig: administered as an IV infusion

Interventions

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Fluorouracil (5-FU)

5-FU: administered as an IV infusion

Intervention Type DRUG

Capecitabine

Capecitabine: administered orally

Intervention Type DRUG

Durvalumab

Durvalumab: administered as an IV infusion

Intervention Type BIOLOGICAL

Oxaliplatin

Oxaliplatin: administered as an IV infusion

Intervention Type DRUG

Trastuzumab

Trastuzumab: administered as an IV infusion

Intervention Type BIOLOGICAL

Trastuzumab deruxtecan

T-DXd: administered as an IV infusion

Intervention Type DRUG

Cisplatin

Cisplatin: administered as an IV infusion

Intervention Type DRUG

Pembrolizumab

Pembrolizumab: administered as an IV infusion

Intervention Type BIOLOGICAL

Volrustomig

Volrustomig: administered as an IV infusion

Intervention Type BIOLOGICAL

Rilvegostomig

Rilvegostomig: administered as an IV infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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MEDI4736 DS-8201a, Enhertu MEDI5752 AZD2936

Eligibility Criteria

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Inclusion 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,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
3. 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
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.

Exclusion Criteria

1. 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.
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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Santa Monica, California, United States

Site Status WITHDRAWN

Research Site

Westwood, Kansas, United States

Site Status WITHDRAWN

Research Site

Baltimore, Maryland, United States

Site Status RECRUITING

Research Site

Boston, Massachusetts, United States

Site Status WITHDRAWN

Research Site

Boston, Massachusetts, United States

Site Status RECRUITING

Research Site

Ann Arbor, Michigan, United States

Site Status WITHDRAWN

Research Site

New York, New York, United States

Site Status RECRUITING

Research Site

Durham, North Carolina, United States

Site Status WITHDRAWN

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Fairfax, Virginia, United States

Site Status WITHDRAWN

Research Site

Florianópolis, , Brazil

Site Status WITHDRAWN

Research Site

Londrina, , Brazil

Site Status RECRUITING

Research Site

Natal, , Brazil

Site Status WITHDRAWN

Research Site

Porto Alegre, , Brazil

Site Status WITHDRAWN

Research Site

Ribeirão Preto, , Brazil

Site Status ACTIVE_NOT_RECRUITING

Research Site

Rio de Janeiro, , Brazil

Site Status WITHDRAWN

Research Site

Santa Maria, , Brazil

Site Status RECRUITING

Research Site

São Jose Do Rio Preto, , Brazil

Site Status RECRUITING

Research Site

São Paulo, , Brazil

Site Status WITHDRAWN

Research Site

São Paulo, , Brazil

Site Status WITHDRAWN

Research Site

São Paulo, , Brazil

Site Status ACTIVE_NOT_RECRUITING

Research Site

Edmonton, Alberta, Canada

Site Status WITHDRAWN

Research Site

Ottawa, Ontario, Canada

Site Status WITHDRAWN

Research Site

Toronto, Ontario, Canada

Site Status WITHDRAWN

Research Site

Toronto, Ontario, Canada

Site Status RECRUITING

Research Site

Montreal, Quebec, Canada

Site Status RECRUITING

Research Site

Québec, Quebec, Canada

Site Status RECRUITING

Research Site

Chengdu, , China

Site Status RECRUITING

Research Site

Guangzhou, , China

Site Status RECRUITING

Research Site

Guiyang, , China

Site Status WITHDRAWN

Research Site

Hangzhou, , China

Site Status WITHDRAWN

Research Site

Hefei, , China

Site Status RECRUITING

Research Site

Hefei, , China

Site Status WITHDRAWN

Research Site

Shanghai, , China

Site Status RECRUITING

Research Site

Shanghai, , China

Site Status WITHDRAWN

Research Site

Shanghai, , China

Site Status RECRUITING

Research Site

Shanghai, , China

Site Status WITHDRAWN

Research Site

Shenyang, , China

Site Status RECRUITING

Research Site

Ürümqi, , China

Site Status WITHDRAWN

Research Site

Wuhan, , China

Site Status RECRUITING

Research Site

Xiamen, , China

Site Status WITHDRAWN

Research Site

Zhengzhou, , China

Site Status RECRUITING

Research Site

Frankfurt, , Germany

Site Status RECRUITING

Research Site

Frankfurt, , Germany

Site Status RECRUITING

Research Site

Hamburg, , Germany

Site Status RECRUITING

Research Site

Leipzig, , Germany

Site Status RECRUITING

Research Site

Mannheim, , Germany

Site Status RECRUITING

Research Site

München, , Germany

Site Status RECRUITING

Research Site

Milan, , Italy

Site Status RECRUITING

Research Site

Milan, , Italy

Site Status RECRUITING

Research Site

Napoli, , Italy

Site Status RECRUITING

Research Site

Padua, , Italy

Site Status RECRUITING

Research Site

Roma, , Italy

Site Status RECRUITING

Research Site

Verona, , Italy

Site Status RECRUITING

Research Site

Chūōku, , Japan

Site Status RECRUITING

Research Site

Kashiwa, , Japan

Site Status RECRUITING

Research Site

Kita-gun, , Japan

Site Status RECRUITING

Research Site

Ota-shi, , Japan

Site Status RECRUITING

Research Site

Amsterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Research Site

Amsterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Research Site

Utrecht, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Research Site

Gdansk, , Poland

Site Status RECRUITING

Research Site

Konin, , Poland

Site Status RECRUITING

Research Site

Koszalin, , Poland

Site Status RECRUITING

Research Site

Krakow, , Poland

Site Status RECRUITING

Research Site

Lublin, , Poland

Site Status WITHDRAWN

Research Site

Opole, , Poland

Site Status WITHDRAWN

Research Site

Tomaszów Mazowiecki, , Poland

Site Status WITHDRAWN

Research Site

Warsaw, , Poland

Site Status RECRUITING

Research Site

Kostroma, , Russia

Site Status SUSPENDED

Research Site

Moscow, , Russia

Site Status SUSPENDED

Research Site

Moscow, , Russia

Site Status TERMINATED

Research Site

Moscow, , Russia

Site Status SUSPENDED

Research Site

Moscow, , Russia

Site Status TERMINATED

Research Site

Novosibirsk, , Russia

Site Status SUSPENDED

Research Site

Saint Petersburg, , Russia

Site Status COMPLETED

Research Site

Saint Petersburg, , Russia

Site Status SUSPENDED

Research Site

Saint Petersburg, , Russia

Site Status SUSPENDED

Research Site

Saint Petersburg, , Russia

Site Status COMPLETED

Research Site

Seongnam-si, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status RECRUITING

Research Site

Madrid, , Spain

Site Status RECRUITING

Research Site

Madrid, , Spain

Site Status RECRUITING

Research Site

Santander, , Spain

Site Status RECRUITING

Research Site

Seville, , Spain

Site Status RECRUITING

Research Site

Kaohsiung City, , Taiwan

Site Status RECRUITING

Research Site

Kaohsiung City, , Taiwan

Site Status WITHDRAWN

Research Site

Tainan, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Research Site

Taoyuan District, , Taiwan

Site Status RECRUITING

Research Site

Cambridge, , United Kingdom

Site Status RECRUITING

Research Site

Dundee, , United Kingdom

Site Status RECRUITING

Research Site

London, , United Kingdom

Site Status RECRUITING

Research Site

Manchester, , United Kingdom

Site Status RECRUITING

Research Site

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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Taiwan United Kingdom United States Brazil Canada China Germany Italy Japan Netherlands Poland Russia South Korea Spain

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

Other Identifiers

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2019-004483-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D967LC00001

Identifier Type: -

Identifier Source: org_study_id

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