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

NCT04379596 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: D967LC000012019-004483-22
• Study Type: interventional
• Target: 450
• Locations: 14 countries
• Sites: 100

Brief 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 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

Keywords

Gastric Cancer; Esophageal Cancer; Carcinoma; HER2; Trastuzumab; Deruxtecan; T-DXd; DS-8201a; Gastroesophageal Cancer; Adenocarcinoma

Outcome Measures

Primary Outcomes (6)

• 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

  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

  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.

  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.

  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.

  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.

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

Secondary Outcomes (19)

• Part 1: Objective Response Rate (ORR)

  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)

  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

  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

  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

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

Study Arms (18)

Arm 1A

EXPERIMENTAL

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

Drug: Fluorouracil (5-FU); Drug: Trastuzumab deruxtecan

Arm 1B

EXPERIMENTAL

T-DXd and capecitabine

Drug: Capecitabine; Drug: Trastuzumab deruxtecan

Arm 1C

EXPERIMENTAL

T-DXd and durvalumab

Biological: Durvalumab; Drug: Trastuzumab deruxtecan

Arm 1D(b)

EXPERIMENTAL

T-DXd, capecitabine, and oxaliplatin

Drug: Capecitabine; Drug: Oxaliplatin; Drug: Trastuzumab deruxtecan

Arm 1E(a)

EXPERIMENTAL

T-DXd, 5-FU, and durvalumab

Drug: Fluorouracil (5-FU); Biological: Durvalumab; Drug: Trastuzumab deruxtecan

Arm 1E(b)

EXPERIMENTAL

T-DXd, capecitabine, and durvalumab

Drug: Capecitabine; Biological: Durvalumab; Drug: Trastuzumab deruxtecan

Arm 2A

ACTIVE COMPARATOR

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

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Oxaliplatin; Biological: Trastuzumab; Drug: Cisplatin

Arm 2B

EXPERIMENTAL

T-DXd monotherapy

Drug: Trastuzumab deruxtecan

Arm 2C

EXPERIMENTAL

T-DXd, 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan

Arm 2D

EXPERIMENTAL

T-DXd, pembrolizumab and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Pembrolizumab

Arm 2E

EXPERIMENTAL

T-DXd and pembrolizumab

Drug: Trastuzumab deruxtecan; Biological: Pembrolizumab

Arm 2F

EXPERIMENTAL

T-DXd, pembrolizumab and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Pembrolizumab

Arm 3A

EXPERIMENTAL

T-DXd, Volrustomig and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig

Arm 3B

EXPERIMENTAL

T-DXd, Volrustomig and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig

Arm 4A

EXPERIMENTAL

T-DXd, Rilvegostomig and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Rilvegostomig

Arm 4B

EXPERIMENTAL

T-DXd, Rilvegostomig and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Rilvegostomig

Part 5 Main Cohort

EXPERIMENTAL

T-DXd, Volrustomig and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig

Part 5 Cohort 2

EXPERIMENTAL

T-DXd, Volrustomig and 5-FU or capecitabine

Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Trastuzumab deruxtecan; Biological: Volrustomig

Interventions

Fluorouracil (5-FU) DRUG

5-FU: administered as an IV infusion

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

Capecitabine DRUG

Capecitabine: administered orally

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

Durvalumab BIOLOGICAL

Durvalumab: administered as an IV infusion

Also known as: MEDI4736

Arm 1C; Arm 1E(a); Arm 1E(b)

Oxaliplatin DRUG

Oxaliplatin: administered as an IV infusion

Arm 1D(b); Arm 2A

Trastuzumab BIOLOGICAL

Trastuzumab: administered as an IV infusion

Arm 2A

Trastuzumab deruxtecan DRUG

T-DXd: administered as an IV infusion

Also known as: DS-8201a, Enhertu

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

Cisplatin DRUG

Cisplatin: administered as an IV infusion

Arm 2A

Pembrolizumab BIOLOGICAL

Pembrolizumab: administered as an IV infusion

Arm 2D; Arm 2E; Arm 2F

Volrustomig BIOLOGICAL

Volrustomig: administered as an IV infusion

Also known as: MEDI5752

Arm 3A; Arm 3B; Part 5 Cohort 2; Part 5 Main Cohort

Rilvegostomig BIOLOGICAL

Rilvegostomig: administered as an IV infusion

Also known as: AZD2936

Arm 4A; Arm 4B

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 qualify 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo: collaborator

Study Sites (100)

Research Site

Santa Monica, California, 90404, United States

WITHDRAWN

Research Site

Westwood, Kansas, 66205, United States

WITHDRAWN

Research Site

Baltimore, Maryland, 21287, United States

RECRUITING

Research Site

Boston, Massachusetts, 02114, United States

WITHDRAWN

Research Site

Boston, Massachusetts, 02215, United States

RECRUITING

Research Site

Ann Arbor, Michigan, 48109, United States

WITHDRAWN

Research Site

New York, New York, 10065, United States

RECRUITING

Research Site

Durham, North Carolina, 27710, United States

WITHDRAWN

Research Site

Houston, Texas, 77090, United States

RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

WITHDRAWN

Research Site

Florianópolis, 88020-210, Brazil

WITHDRAWN

Research Site

Londrina, 86015-520, Brazil

COMPLETED

Research Site

Natal, 59075-740, Brazil

WITHDRAWN

Research Site

Porto Alegre, 90160-093, Brazil

WITHDRAWN

Research Site

Ribeirão Preto, 14051-140, Brazil

ACTIVE NOT RECRUITING

Research Site

Rio de Janeiro, 22793-080, Brazil

WITHDRAWN

Research Site

Santa Maria, 97015-450, Brazil

RECRUITING

Research Site

São Jose Do Rio Preto, 15090-000, Brazil

RECRUITING

Research Site

São Paulo, 01509-900, Brazil

WITHDRAWN

Research Site

São Paulo, 03102-002, Brazil

WITHDRAWN

Research Site

São Paulo, 045202-001, Brazil

ACTIVE NOT RECRUITING

Research Site

Edmonton, Alberta, T6G 1Z2, Canada

WITHDRAWN

Research Site

Ottawa, Ontario, K1H 8L6, Canada

WITHDRAWN

Research Site

Toronto, Ontario, M4N 3M5, Canada

WITHDRAWN

Research Site

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Research Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Research Site

Québec, Quebec, G1J 1Z4, Canada

RECRUITING

Research Site

Chengdu, 610042, China

RECRUITING

Research Site

Guangzhou, 510062, China

RECRUITING

Research Site

Guiyang, 550002, China

WITHDRAWN

Research Site

Hangzhou, 310022, China

WITHDRAWN

Research Site

Hefei, 230001, China

RECRUITING

Research Site

Hefei, 230601, China

WITHDRAWN

Research Site

Shanghai, 200025, China

RECRUITING

Research Site

Shanghai, 200031, China

WITHDRAWN

Research Site

Shanghai, 200032, China

RECRUITING

Research Site

Shanghai, 200050, China

WITHDRAWN

Research Site

Shenyang, 110001, China

RECRUITING

Research Site

Ürümqi, 830000, China

WITHDRAWN

Research Site

Wuhan, 430000, China

RECRUITING

Research Site

Xiamen, 361003, China

WITHDRAWN

Research Site

Zhengzhou, 450008, China

RECRUITING

Research Site

Frankfurt, 60488, Germany

RECRUITING

Research Site

Frankfurt, 60590, Germany

RECRUITING

Research Site

Hamburg, 20249, Germany

RECRUITING

Research Site

Leipzig, 04103, Germany

RECRUITING

Research Site

Mannheim, 68167, Germany

RECRUITING

Research Site

München, 81675, Germany

RECRUITING

Research Site

Milan, 20133, Italy

RECRUITING

Research Site

Milan, 20162, Italy

RECRUITING

Research Site

Naples, 80131, Italy

RECRUITING

Research Site

Padua, 35128, Italy

RECRUITING

Research Site

Roma, 00168, Italy

RECRUITING

Research Site

Verona, 37134, Italy

RECRUITING

Research Site

Chūōku, 104-0045, Japan

RECRUITING

Research Site

Kashiwa, 277-8577, Japan

RECRUITING

Research Site

Kita-gun, 761-0793, Japan

RECRUITING

Research Site

Ota-shi, 373-8550, Japan

RECRUITING

Research Site

Amsterdam, 1066CX, Netherlands

RECRUITING

Research Site

Amsterdam, 1081 HV, Netherlands

RECRUITING

Research Site

Utrecht, 3584CG, Netherlands

RECRUITING

Research Site

Gdansk, 80-214, Poland

RECRUITING

Research Site

Konin, 62-500, Poland

RECRUITING

Research Site

Koszalin, 75-581, Poland

RECRUITING

Research Site

Krakow, 31-501, Poland

RECRUITING

Research Site

Lublin, 20-090, Poland

WITHDRAWN

Research Site

Opole, 45-061, Poland

WITHDRAWN

Research Site

Tomaszów Mazowiecki, 97-200, Poland

WITHDRAWN

Research Site

Warsaw, 02-034, Poland

RECRUITING

Research Site

Kostroma, 156005, Russia

SUSPENDED

Research Site

Moscow, 115478, Russia

SUSPENDED

Research Site

Moscow, 125284, Russia

TERMINATED

Research Site

Moscow, 143423, Russia

SUSPENDED

Research Site

Moscow, 143442, Russia

TERMINATED

Research Site

Novosibirsk, 630099, Russia

SUSPENDED

Research Site

Saint Petersburg, 195271, Russia

COMPLETED

Research Site

Saint Petersburg, 196603, Russia

SUSPENDED

Research Site

Saint Petersburg, 197022, Russia

SUSPENDED

Research Site

Saint Petersburg, 197758, Russia

COMPLETED

Research Site

Seongnam-si, 13620, South Korea

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 03722, South Korea

RECRUITING

Research Site

Seoul, 05505, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Barcelona, 08035, Spain

RECRUITING

Research Site

Madrid, 28007, Spain

RECRUITING

Research Site

Madrid, 28034, Spain

RECRUITING

Research Site

Santander, 39008, Spain

RECRUITING

Research Site

Seville, 41013, Spain

RECRUITING

Research Site

Kaohsiung City, 80756, Taiwan

RECRUITING

Research Site

Kaohsiung City, 83301, Taiwan

WITHDRAWN

Research Site

Tainan, 704, Taiwan

RECRUITING

Research Site

Taipei, 10002, Taiwan

RECRUITING

Research Site

Taipei, 11217, Taiwan

RECRUITING

Research Site

Taoyuan District, 333, Taiwan

RECRUITING

Research Site

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Research Site

Dundee, DD1 9SY, United Kingdom

RECRUITING

Research Site

London, NW1 2PG, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

Research Site

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Carcinoma; Adenocarcinoma

Interventions

Fluorouracil; Capecitabine; durvalumab; Oxaliplatin; Trastuzumab; trastuzumab deruxtecan; Cisplatin; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 5, 2020
• First Posted: May 7, 2020
• Study Start: June 3, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: Study start to completion date
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (10); KR (5); ES (5); IT (6); GB (5); PL (8); BR (11); CA (6); DE (6); RU (10); CN (15); NL (3); JP (4); TW (6)