Clinical Trials /

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

NCT04379596

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2+ Gastric Cancer (DESTINY-Gastric03)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: D967LC00001
  • NCT ID: NCT04379596

Conditions

  • Gastric Cancer

Interventions

DrugSynonymsArms
Fluorouracil (5-FU)Arm 1A
CapecitabineArm 1B
DurvalumabMEDI4736Arm 1C
OxaliplatinArm 1D
TrastuzumabArm 2A
Trastuzumab deruxtecanDS-8201aArm 1A
CisplatinArm 2A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm 1AExperimentalT-DXd and 5-fluorouracil (5-FU)
  • Fluorouracil (5-FU)
  • Trastuzumab deruxtecan
Arm 1BExperimentalT-DXd and capecitabine
  • Capecitabine
  • Trastuzumab deruxtecan
Arm 1CExperimentalT-DXd and durvalumab
  • Durvalumab
  • Trastuzumab deruxtecan
Arm 1DExperimentalT-DXd and 5-FU or capecitabine and oxaliplatin
  • Fluorouracil (5-FU)
  • Capecitabine
  • Oxaliplatin
  • Trastuzumab deruxtecan
Arm 1EExperimentalT-DXd, durvalumab and 5-FU or capecitabine
  • Fluorouracil (5-FU)
  • Capecitabine
  • Durvalumab
  • Trastuzumab deruxtecan
Arm 2AActive ComparatorTrastuzumab, 5-FU/capecitabine, and cisplatin/oxaliplatin
  • Fluorouracil (5-FU)
  • Capecitabine
  • Oxaliplatin
  • Trastuzumab
  • Cisplatin
Arm 2BExperimentalT-DXd monotherapy
  • Trastuzumab deruxtecan
Arm 2CExperimentalT-DXd, 5-FU or capecitabine, and oxaliplatin
  • Fluorouracil (5-FU)
  • Capecitabine
  • Oxaliplatin
  • Trastuzumab deruxtecan
Arm 2DExperimentalT-DXd, 5-FU or capecitabine, and durvalumab
  • Fluorouracil (5-FU)
  • Capecitabine
  • Durvalumab
  • Trastuzumab deruxtecan

Eligibility 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.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

Secondary Outcome Measures

Measure:Part 1: Objective Response Rate (ORR)
Time Frame:An average of approximately 12 months.
Safety Issue:
Description:Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.
Measure: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.
Safety Issue:
Description:Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Measure:Duration of Response (DoR)
Time Frame:An average of approximately 18 months.
Safety Issue:
Description:DOR is defined as the time from the date of first documented response until the date of documented progression or death
Measure:Disease Control Rate (DCR)
Time Frame:An average of approximately 18 months.
Safety Issue:
Description:DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD)
Measure:Progression Free Survival (PFS)
Time Frame:An average of approximately 18 months.
Safety Issue:
Description: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
Measure:Overall survival (OS)
Time Frame:An average of approximately 30 months.
Safety Issue:
Description:OS is the time from date of treatment assignment (Part 1) or date of randomization (Part 2) until death due to any cause
Measure:Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms
Time Frame:An average of approximately 24 months.
Safety Issue:
Description: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
Measure:Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab
Time Frame:An average of approximately 24 months.
Safety Issue:
Description:Individual participant data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab.
Measure:Presence of ADAs for T-DXd and durvalumab (in study arms including T-DXd and durvalumab)
Time Frame:An average of approximately 24 months.
Safety Issue:
Description:Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd and durvalumab.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Gastric Cancer
  • Carcinoma
  • HER2
  • Trastuzumab
  • Deruxtecan
  • T-DXd
  • DS-8201a

Last Updated

May 5, 2020