Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)
- Registration Number
- NCT04379596
- Lead Sponsor
- 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 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
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 413
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3B Fluorouracil (5-FU) T-DXd, Volrustomig and 5-FU or capecitabine Arm 1C Durvalumab T-DXd and durvalumab Arm 1C Trastuzumab deruxtecan T-DXd and durvalumab Arm 1A Fluorouracil (5-FU) T-DXd and 5-fluorouracil (5-FU) Arm 1E(b) Capecitabine T-DXd, capecitabine, and durvalumab Arm 1B Capecitabine T-DXd and capecitabine Arm 1B Trastuzumab deruxtecan T-DXd and capecitabine Arm 1D(b) Capecitabine T-DXd, capecitabine, and oxaliplatin Arm 1E(a) Fluorouracil (5-FU) T-DXd, 5-FU, and durvalumab Arm 1E(b) Durvalumab T-DXd, capecitabine, and durvalumab Arm 2A Fluorouracil (5-FU) Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin Arm 3A Fluorouracil (5-FU) T-DXd, Volrustomig and 5-FU or capecitabine Arm 2A Cisplatin Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin Arm 2C Capecitabine T-DXd, 5-FU or capecitabine Arm 2D Pembrolizumab T-DXd, pembrolizumab and 5-FU or capecitabine Arm 2F Capecitabine T-DXd, pembrolizumab and 5-FU or capecitabine Arm 2D Fluorouracil (5-FU) T-DXd, pembrolizumab and 5-FU or capecitabine Arm 2E Pembrolizumab T-DXd and pembrolizumab Arm 2D Trastuzumab deruxtecan T-DXd, pembrolizumab and 5-FU or capecitabine Arm 2A Trastuzumab Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin Arm 2B Trastuzumab deruxtecan T-DXd monotherapy Arm 2C Fluorouracil (5-FU) T-DXd, 5-FU or capecitabine Arm 2D Capecitabine T-DXd, pembrolizumab and 5-FU or capecitabine Arm 3A Capecitabine T-DXd, Volrustomig and 5-FU or capecitabine Arm 3B Capecitabine T-DXd, Volrustomig and 5-FU or capecitabine Arm 2C Trastuzumab deruxtecan T-DXd, 5-FU or capecitabine Arm 2F Fluorouracil (5-FU) T-DXd, pembrolizumab and 5-FU or capecitabine Arm 3A Trastuzumab deruxtecan T-DXd, Volrustomig and 5-FU or capecitabine Arm 4B Trastuzumab deruxtecan T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 2F Trastuzumab deruxtecan T-DXd, pembrolizumab and 5-FU or capecitabine Arm 2F Pembrolizumab T-DXd, pembrolizumab and 5-FU or capecitabine Arm 3A Volrustomig T-DXd, Volrustomig and 5-FU or capecitabine Arm 3B Volrustomig T-DXd, Volrustomig and 5-FU or capecitabine Arm 4A Trastuzumab deruxtecan T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 4A Fluorouracil (5-FU) T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 4A Capecitabine T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 4B Rilvegostomig T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 4B Fluorouracil (5-FU) T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 4A Rilvegostomig T-DXd, Rilvegostomig and 5-FU or capecitabine Arm 1A Trastuzumab deruxtecan T-DXd and 5-fluorouracil (5-FU) Arm 1D(b) Oxaliplatin T-DXd, capecitabine, and oxaliplatin Arm 1D(b) Trastuzumab deruxtecan T-DXd, capecitabine, and oxaliplatin Arm 1E(a) Durvalumab T-DXd, 5-FU, and durvalumab Arm 1E(a) Trastuzumab deruxtecan T-DXd, 5-FU, and durvalumab Arm 2A Oxaliplatin Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin Arm 1E(b) Trastuzumab deruxtecan T-DXd, capecitabine, and durvalumab Arm 2A Capecitabine Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin Arm 2E Trastuzumab deruxtecan T-DXd and pembrolizumab Arm 3B Trastuzumab deruxtecan T-DXd, Volrustomig and 5-FU or capecitabine Arm 4B Capecitabine T-DXd, Rilvegostomig and 5-FU or capecitabine
- Primary Outcome Measures
Name Time Method Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0 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: Changes from baseline in electrocardiogram (ECG) results Safety will be assessed up to the follow-up period, approximately 24 months. Changes in ECG results compared to baseline results.
Part 1: Changes from baseline in laboratory parameters 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 Safety will be assessed up to the follow-up period, approximately 24 months. Changes in vital signs results compared to baseline results.
Part 1: Ocurrence of dose-limiting toxicities (DLTs) Safety will be assessed up to the follow-up period, approximately 24 months. Occurrence of dose limiting toxicities
Part 2, Part 3 and Part 4: Endpoint assessed by Investigator per RECIST v1.1: Confirmed Objective Response Rate (ORR) (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
Name Time Method Part 2, Part 3 and Part 4: Changes from baseline in laboratory parameters 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 1: Objective Response Rate (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.
Part 2, Part 3 and Part 4: Changes from baseline in electrocardiogram (ECG) results Safety will be assessed up to follow-up period, approximately 24 months Changes in ECG results compared to baseline results.
Disease Control Rate (DCR) 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)
Comparison of PFS 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
Part 2, Part 3 and Part 4: Changes from baseline in vital signs Safety will be assessed up to follow-up period, approximately 24 months Changes in vital signs results compared to baseline results.
Duration of Response (DoR) 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
Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms 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
Comparison of ORR 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 DoR 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
Part 2, Part 3 and Part 4: Occurrence of adverse events (AEs) and serious adverse events (SAEs) 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, Part 3 and Part 4: Changes from baseline in body weight Safety will be assessed up to follow-up period, approximately 24 months Changes in body weight in kilograms compared to baseline results.
Progression Free Survival (PFS) 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
Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab 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.
Comparison of OS 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
Overall survival (OS) 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
Presence of ADAs for T-DXD, durvalumab, volrustomig and rilvegostomig (in study arms including T-DXd and durvalumab, and T-DXd and volrustomig, and T-DXd and rilvegostomig respectively) 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 volrustomig and rilvegostomig in study arms including T-DXd in combination with volrustomig and T-DXd in combination with rilvegostomig 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 rilvegostomig and volrustomig
Comparison of DCR 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
Trial Locations
- Locations (1)
Research Site
🇬🇧Sutton, United Kingdom