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

ConditionGastric Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-130
SponsorAstraZeneca

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male and female participants must be at least 18 years of age. Other age restrictions may apply as per local regulations

Locally advanced, unresectable, or metastatic disease based on most recent imaging

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

For Part 3b,4b and Part 5, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results

Disqualifiers

Part 1 to 4: History of active primary immunodeficiency, known HIV, active chronic, or past hepatitis B infection, or hepatitis C infection. Part 5: evidence of active, uncontroled HIV, 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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Fluorouracil (5-FU)

    Drug

    5-FU: administered as an IV infusion

  • Capecitabine

    Drug

    Capecitabine: administered orally

  • Durvalumab

    Biological/Vaccine

    Durvalumab: administered as an IV infusion

  • Oxaliplatin

    Drug

    Oxaliplatin: administered as an IV infusion

  • Trastuzumab

    Biological/Vaccine

    Trastuzumab: administered as an IV infusion

  • Trastuzumab deruxtecan

    Drug

    T-DXd: administered as an IV infusion

  • Cisplatin

    Drug

    Cisplatin: administered as an IV infusion

  • Pembrolizumab

    Biological/Vaccine

    Pembrolizumab: administered as an IV infusion

  • Volrustomig

    Biological/Vaccine

    Volrustomig: administered as an IV infusion

  • Rilvegostomig

    Biological/Vaccine

    Rilvegostomig: administered as an IV infusion

Treatment groups

450 Participants
are divided into 18 treatment groups

18

Treatment groups

See each treatment group below.

Group A: Arm 1AExperimental treatment 2 interventions
Group B: Arm 1BExperimental treatment 2 interventions
Group C: Arm 1CExperimental treatment 2 interventions
Group D: Arm 1D(b)Experimental treatment 3 interventions
Group E: Arm 1E(a)Experimental treatment 3 interventions
Group F: Arm 1E(b)Experimental treatment 3 interventions
Group G: Arm 2AActive comparator 5 interventions
Group H: Arm 2BExperimental treatment 1 intervention
Group I: Arm 2CExperimental treatment 3 interventions
Group J: Arm 2DExperimental treatment 4 interventions
Group K: Arm 2EExperimental treatment 2 interventions
Group L: Arm 2FExperimental treatment 4 interventions
Group M: Arm 3AExperimental treatment 4 interventions
Group N: Arm 3BExperimental treatment 4 interventions
Group O: Arm 4AExperimental treatment 4 interventions
Group P: Arm 4BExperimental treatment 4 interventions
Group Q: Part 5 Main CohortExperimental treatment 4 interventions
Group R: Part 5 Cohort 2Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0

Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

Time frame
Safety will be assessed up to the follow-up period, approximately 24 months.
2

Part 1: Ocurrence of dose-limiting toxicities (DLTs)

Occurrence of dose limiting toxicities

Time frame
Safety will be assessed up to the follow-up period, approximately 24 months.
3

Part 1: Changes from baseline in laboratory parameters

Changes in laboratory parameters (every in appropriate units) compared to baseline results.

Time frame
Safety will be assessed up to the follow-up period, approximately 24 months.
4

Part 1: Changes from baseline in vital signs

Changes in vital signs results compared to baseline results.

Time frame
Safety will be assessed up to the follow-up period, approximately 24 months.

Secondary outcomes

1

Part 1: Objective Response Rate (ORR)

Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Time frame
Efficacy will be assessed at an average of approximately 12 months
2

Part 2, Part 3, Part 4 and Part 5: Occurrence of adverse events (AEs) and serious adverse events (SAEs)

Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

Time frame
Safety will be assessed up to follow-up period, approximately 24 months
3

Part 2, Part 3, Part 4 and Part 5: Changes from baseline in laboratory parameters

Changes in laboratory parameters (every in appropriate units) compared to baseline results.

Time frame
Safety will be assessed up to follow-up period, approximately 24 months
4

Part 2, Part 3, Part 4 and Part 5: Changes from baseline in vital signs

Changes in vital signs results compared to baseline results.

Time frame
Safety will be assessed up to follow-up period, approximately 24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

AstraZeneca

Lead sponsor

Daiichi Sankyo

Collaborator

Source ClinicalTrials.gov
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