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JOURNAL ONKOLOGIE – STUDIE
DG-03

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

Rekrutierend

NCT-Nummer:
NCT04379596

Studienbeginn:
Juni 2020

Letztes Update:
07.08.2024

Wirkstoff:
Fluorouracil (5-FU), Capecitabin, Durvalumab, Oxaliplatin, Trastuzumab, Trastuzumab Deruxtecan (T-DXd), Cisplatin, Pembrolizumab, Volrustomig, Rilvegostomig

Indikation (Clinical Trials):
Stomach Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
AstraZeneca

Collaborator:
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 100)

Research Site
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
14051-140 Ribeirão Preto
BrazilAktiv, nicht rekrutierend» Google-Maps
Research Site
15090-000 São Jose do Rio Preto
BrazilRekrutierend» Google-Maps
Research Site
045202-001 São Paulo
BrazilAktiv, nicht rekrutierend» Google-Maps
Research Site
13620 Seongnam-si
Korea, Republic ofRekrutierend» Google-Maps
Research Site
195271 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
Research Site
197022 Saint-Petersburg
Russian FederationSchwebend» Google-Maps
Research Site
197758 Saint-Petersburg
Russian FederationSchwebend» Google-Maps
Research Site
196603 Sankt-Peterburg
Russian FederationSchwebend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion criteria:

1. Male and female participants must be at least 18 years of age. Other age

restrictions may apply as per local regulations

2. Disease Characteristics:

1. Locally advanced, unresectable, or metastatic disease based on most recent

imaging

2. 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

3. For Part 3b and 4b, pathologically documented adenocarcinoma of the

stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local

tissue testing results

3. For Part 1, progression on or after at least one prior trastuzumabcontaining regimen

For Part 2, Part 3 and Part 4, 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] and Part 4 [Arm

4B])) status

4. Has measurable target disease assessed by the Investigator based on RECIST version

1.1

5. Has protocol defined adequate bone marrow and 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.

Exclusion criteria:

1. History of active primary immunodeficiency, known HIV, active chronic, or past

hepatitis B infection, or hepatitis C infection.

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.

Studien-Rationale

Primary outcome:

1. 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

2. 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

3. 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.

4. 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.

5. 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.

6. Part 2, Part 3 and Part 4: 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:

1. 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.

2. Part 2, Part 3 and Part 4: 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

3. Part 2, Part 3 and Part 4: 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.

4. Part 2, Part 3 and Part 4: 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.

5. Part 2, Part 3 and Part 4: 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.

6. Part 2, Part 3 and Part 4: 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.

7. 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

8. 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)

9. 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

10. 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

11. 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

12. 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.

13. 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) (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.

14. Serum concentrations of volrustomig and rilvegostomig in study arms including T-DXd in combination with volrustomig and T-DXd in combination with rilvegostomig (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 rilvegostomig and volrustomig

15. 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

16. 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

17. 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

18. 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

19. 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

Studien-Arme

  • Experimental: Arm 1A
    T-DXd and 5-fluorouracil (5-FU)
  • Experimental: Arm 1B
    T-DXd and capecitabine
  • Experimental: Arm 1C
    T-DXd and durvalumab
  • Experimental: Arm 1D(b)
    T-DXd, capecitabine, and oxaliplatin
  • Experimental: Arm 1E(a)
    T-DXd, 5-FU, and durvalumab
  • Experimental: Arm 1E(b)
    T-DXd, capecitabine, and durvalumab
  • Active Comparator: Arm 2A
    Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin
  • Experimental: Arm 2B
    T-DXd monotherapy
  • Experimental: Arm 2C
    T-DXd, 5-FU or capecitabine
  • Experimental: Arm 2D
    T-DXd, pembrolizumab and 5-FU or capecitabine
  • Experimental: Arm 2E
    T-DXd and pembrolizumab
  • Experimental: Arm 2F
    T-DXd, pembrolizumab and 5-FU or capecitabine
  • Experimental: Arm 3A
    T-DXd, Volrustomig and 5-FU or capecitabine
  • Experimental: Arm 3B
    T-DXd, Volrustomig and 5-FU or capecitabine
  • Experimental: Arm 4A
    T-DXd, Rilvegostomig and 5-FU or capecitabine
  • Experimental: Arm 4B
    T-DXd, Rilvegostomig and 5-FU or capecitabine

Geprüfte Regime

  • Fluorouracil (5-FU):
    5-FU: administered as an IV infusion
  • Capecitabine:
    Capecitabine: administered orally
  • Durvalumab (MEDI4736):
    Durvalumab: administered as an IV infusion
  • Oxaliplatin:
    Oxaliplatin: administered as an IV infusion
  • Trastuzumab:
    Trastuzumab: administered as an IV infusion
  • Trastuzumab deruxtecan (DS-8201a):
    T-DXd: administered as an IV infusion
  • Cisplatin:
    Cisplatin: administered as an IV infusion
  • Pembrolizumab:
    Pembrolizumab: administered as an IV infusion
  • Volrustomig (MEDI5752):
    Volrustomig: administered as an IV infusion
  • Rilvegostomig (AZD2936):
    Rilvegostomig: administered as an IV infusion

Quelle: ClinicalTrials.gov


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