Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03) (DG-03)
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| ClinicalTrials.gov Identifier: NCT04379596 |
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Recruitment Status :
Recruiting
First Posted : May 7, 2020
Last Update Posted : October 13, 2023
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Sponsor:
AstraZeneca
Collaborator:
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
Information provided by (Responsible Party):
AstraZeneca
- Study Details
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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.
| 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 Biological: Pembrolizumab Biological: MEDI5752 | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 357 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | The study will consist of 2 phases: a dose escalation phase (Part 1) and dose expansion phases (Part 2 and Part 3). 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 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) |
| 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-expressing Gastric Cancer (DESTINY-Gastric-03) |
| Actual Study Start Date : | June 3, 2020 |
| Estimated Primary Completion Date : | September 29, 2025 |
| Estimated Study Completion Date : | September 29, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Stomach Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm 1A
T-DXd and 5-fluorouracil (5-FU)
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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 |
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Experimental: Arm 1B
T-DXd and capecitabine
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Drug: Capecitabine
Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion
Other Name: DS-8201a |
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Experimental: Arm 1C
T-DXd and durvalumab
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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 |
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Experimental: Arm 1D(b)
T-DXd, capecitabine, and oxaliplatin
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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 |
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Experimental: Arm 1E(a)
T-DXd, 5-FU, and durvalumab
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Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion 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 |
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Experimental: Arm 1E(b)
T-DXd, capecitabine, and durvalumab
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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 |
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Active Comparator: Arm 2A
Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin
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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 |
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Experimental: Arm 2B
T-DXd monotherapy
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Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a |
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Experimental: Arm 2C
T-DXd, 5-FU or capecitabine
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Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion Drug: Capecitabine Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion
Other Name: DS-8201a |
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Experimental: Arm 2D
T-DXd, 5-FU or capecitabine, and pembrolizumab
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Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion Drug: Capecitabine Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion
Other Name: DS-8201a Biological: Pembrolizumab Pembrolizumab: administered as an IV infusion |
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Experimental: Arm 2E
T-DXd and pembrolizumab
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Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a Biological: Pembrolizumab Pembrolizumab: administered as an IV infusion |
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Experimental: Arm 2F
T-DXd, chemotherapy (FP) and pembrolizumab
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Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion Drug: Capecitabine Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion
Other Name: DS-8201a Biological: Pembrolizumab Pembrolizumab: administered as an IV infusion |
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Experimental: Arm 3A
T-DXd, FP and BSP (MEDI5752)
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Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion Drug: Capecitabine Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion
Other Name: DS-8201a Biological: MEDI5752 MEDI5752: administered as an IV infusion |
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Experimental: Arm 3B
T-DXd, FP and BSP (MEDI5752)
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Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion Drug: Capecitabine Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion
Other Name: DS-8201a Biological: MEDI5752 MEDI5752: administered as an IV infusion |
Primary Outcome Measures :
- 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 and Part 3: 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 Outcome Measures :
- 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.
- Part 2 and Part 3: 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
- Part 2 and Part 3: 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.
- Part 2 and Part 3: 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.
- Part 2 and Part 3: 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.
- Part 2 and Part 3: 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.
- 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
- 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)
- 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
- 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
- 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
- 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.
- Presence of ADAs for T-DXd and durvalumab and MEDI5752 (in study arms including T-DXd and durvalumab, and T-DXd and MEDI5752, 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.
- Serum concentrations of MEDI5752 in study arms including T-DXd in combination with MEDI5752, [ 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 MEDI5752.
- 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
- 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
- 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
- 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
- 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
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.
| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria:
- Male and female participants must be at least 18 years of age. Other age restrictions may apply as per local regulations
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Disease Characteristics:
- Locally advanced, unresectable, or metastatic disease based on most recent imaging
- For Part 1, 2, 3a, 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, 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 and Part 3, previously untreated for unresectable or metastatic adenocarcinoma of the stomach/GEJ/ esophagus with with HER2-positive (Part 2 and Part 3, Arm 3A) or HER2-low (Part 3, Arm 3B) status
- Has measurable target disease assessed by the Investigator based on RECIST version 1.1
- Has protocol defined adequate 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:
- History of active primary immunodeficiency, known HIV, active 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.
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
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 98 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04379596 |
| Other Study ID Numbers: |
D967LC00001 2019-004483-22 ( EudraCT Number ) |
| First Posted: | May 7, 2020 Key Record Dates |
| Last Update Posted: | October 13, 2023 |
| Last Verified: | October 2023 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Gastric Cancer Esophageal Cancer Carcinoma HER2 Trastuzumab |
Deruxtecan T-DXd DS-8201a Gastroesophageal Cancer |
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 Pembrolizumab Fluorouracil Capecitabine Oxaliplatin Trastuzumab |
Durvalumab Trastuzumab deruxtecan Antineoplastic Agents Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antimetabolites Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Immunoconjugates |