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Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2+ Gastric Cancer (DESTINY-Gastric03) (DG-03)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04379596
Recruitment Status : Not yet recruiting
First Posted : May 7, 2020
Last Update Posted : May 7, 2020
Sponsor:
Collaborator:
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
Information provided by (Responsible Party):
AstraZeneca

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 durvalumab in HER2-positive advanced/metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma patients.

Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or durvalumab 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-positive gastric/GEJ 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.


Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: Fluorouracil (5-FU) Drug: Capecitabine Biological: Durvalumab Drug: Oxaliplatin Biological: Trastuzumab Drug: Trastuzumab deruxtecan Drug: Cisplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study will consist of 2 phases: a dose escalation phase (Part 1) and a dose expansion phase (Part 2). Part 1 will enroll HER2-overexpressing (IHC 3+ or IHC 2+/ISH+), previously treated gastric or gastro-esophageal junction (GEJ) cancer patients, and Part 2 will enroll HER2-overexpressing patients who have not received prior treatment for metastatic 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)
Primary Purpose: Treatment
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 Overexpressing Gastric Cancer (DESTINY-Gastric03)
Estimated Study Start Date : May 25, 2020
Estimated Primary Completion Date : December 27, 2022
Estimated Study Completion Date : December 27, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: Arm 1A
T-DXd and 5-fluorouracil (5-FU)
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 1B
T-DXd and capecitabine
Drug: Capecitabine
Capecitabine: administered orally

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 1C
T-DXd and durvalumab
Biological: Durvalumab
Durvalumab: administered as an IV infusion
Other Name: MEDI4736

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 1D
T-DXd and 5-FU or capecitabine and oxaliplatin
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Drug: Oxaliplatin
Oxaliplatin: administered as an IV infusion

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 1E
T-DXd, durvalumab and 5-FU or capecitabine
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Biological: Durvalumab
Durvalumab: administered as an IV infusion
Other Name: MEDI4736

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Active Comparator: Arm 2A
Trastuzumab, 5-FU/capecitabine, and cisplatin/oxaliplatin
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Drug: Oxaliplatin
Oxaliplatin: administered as an IV infusion

Biological: Trastuzumab
Trastuzumab: administered as an IV infusion

Drug: Cisplatin
Cisplatin: administered as an IV infusion

Experimental: Arm 2B
T-DXd monotherapy
Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 2C
T-DXd, 5-FU or capecitabine, and oxaliplatin
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Drug: Oxaliplatin
Oxaliplatin: administered as an IV infusion

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 2D
T-DXd, 5-FU or capecitabine, and durvalumab
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Biological: Durvalumab
Durvalumab: administered as an IV infusion
Other Name: MEDI4736

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a




Primary Outcome Measures :
  1. Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Safety will be assessed for approximately 24 months from informed consent. ]
    Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

  2. Part 2: Objective Response Rate (ORR) [ Time Frame: 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 Outcome Measures :
  1. Part 1: Objective Response Rate (ORR) [ Time Frame: 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: Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Safety will be assessed for approximately 24 months from informed consent. ]
    Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

  3. Duration of Response (DoR) [ Time Frame: An average of approximately 18 months. ]
    DOR is defined as the time from the date of first documented response until the date of documented progression or death

  4. Disease Control Rate (DCR) [ Time Frame: An average of approximately 18 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)

  5. Progression Free Survival (PFS) [ Time Frame: An average of approximately 18 months. ]
    PFS is the time from date of treatment assignment (Part 1) or date of randomization (Part 2) until the date of objective disease progression or death

  6. Overall survival (OS) [ Time Frame: An average of approximately 30 months. ]
    OS is the time from date of treatment assignment (Part 1) or date of randomization (Part 2) until death due to any cause

  7. Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms [ Time Frame: An average of 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

  8. Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab [ Time Frame: An average of approximately 24 months. ]
    Individual participant data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab.

  9. Presence of ADAs for T-DXd and durvalumab (in study arms including T-DXd and durvalumab) [ Time Frame: An average of 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Male and female participants must be at least 18 years of age (20 years of age in Japan)
  2. Disease Characteristics:

Locally advanced, unresectable, or metastatic disease Pathologically documented adenocarcinoma of the stomach or GEJ with HER2 overexpression (IHC 3+ or ICH 2+/ISH+) 3. For Part 1, progression on or after at least one prior trastuzumab-containing regimen For Part 2, previously untreated for unresectable or metastatic adenocarcinoma of the stomach or GEJ with HER2 overexpression.

4. Has measurable target disease assessed by the Investigator based on RECIST version 1.1 5. Has protocol- defined adequate 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 and for at least 7 months (female) or 4 months (male) after last dose of study drug.

Exclusion criteria:

  1. History of active primary immunodeficiency, known HIV, active HBV or HCV infection, or active tuberculosis.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04379596


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, New York
Research Site
New York, New York, United States, 10065
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M5G 2M9
Germany
Research Site
Berlin, Germany, 13353
Research Site
Frankfurt, Germany, 60488
Research Site
Frankfurt, Germany, 60590
Research Site
Hamburg, Germany, 20246
Research Site
Hamburg, Germany, 20249
Research Site
Leipzig, Germany, 04103
Research Site
Mannheim, Germany, 68167
Research Site
München, Germany, 81675
Italy
Research Site
Milano, Italy, 20133
Research Site
Milano, Italy, 20162
Research Site
Napoli, Italy, 80131
Research Site
Padova, Italy, 35128
Research Site
Verona, Italy, 37134
Korea, Republic of
Research Site
Seongnam, Korea, Republic of, 13620
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 05505
Research Site
Seoul, Korea, Republic of, 06351
Spain
Research Site
Madrid, Spain, 28007
Research Site
Santander, Spain, 39008
Research Site
Sevilla, Spain, 41013
Taiwan
Research Site
Kaohsiung, Taiwan, 80756
Research Site
Taipei, Taiwan, 10002
Research Site
Taipei, Taiwan, 11217
Research Site
Taoyuan, Taiwan, 333
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04379596    
Other Study ID Numbers: D967LC00001
First Posted: May 7, 2020    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Supporting Materials: Informed Consent Form (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.

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AstraZeneca:
Gastric Cancer
Carcinoma
HER2
Trastuzumab
Deruxtecan
T-DXd
DS-8201a
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Trastuzumab
Durvalumab
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological