Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03) - DG-03

Study identifier:D967LC00001

ClinicalTrials.gov identifier:NCT04379596

EudraCT identifier:2019-004483-22

CTIS identifier:N/A

Recruiting

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)

Medical condition

gastric cancer

Phase

Phase 2

Healthy volunteers

Study drug

Fluorouracil (5-FU), Capecitabine, Oxaliplatin, Trastuzumab deruxtecan, Cisplatin

Sex

All

Estimated Enrollment

413

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 03 Jun 2020

Estimated Primary Completion Date: 30 Jul 2026

Estimated Study Completion Date: 30 Jul 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2024 by AstraZeneca

Collaborators

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

Inclusion and exclusion criteria

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:
a/Locally advanced, unresectable, or metastatic disease based on most recent imaging
b/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
c/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.

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Arm 1A T-DXd and 5-fluorouracil (5-FU)	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
Experimental: Arm 1B T-DXd and capecitabine	Drug: Capecitabine Capecitabine: administered orally Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a
Experimental: Arm 1C T-DXd and durvalumab	Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a
Experimental: Arm 1D(b) T-DXd, capecitabine, and oxaliplatin	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
Experimental: Arm 1E(a) T-DXd, 5-FU, and durvalumab	Drug: Fluorouracil (5-FU) 5-FU: administered as an IV infusion Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a
Experimental: Arm 1E(b) T-DXd, capecitabine, and durvalumab	Drug: Capecitabine Capecitabine: administered orally Biological/Vaccine: Durvalumab Durvalumab: administered as an IV infusion Other Name: MEDI4736 Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a
Active Comparator: Arm 2A Trastuzumab, 5-FU or capecitabine, and cisplatin or oxaliplatin	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/Vaccine: Trastuzumab Trastuzumab: administered as an IV infusion Drug: Cisplatin Cisplatin: administered as an IV infusion
Experimental: Arm 2B T-DXd monotherapy	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a
Experimental: Arm 2C T-DXd, 5-FU or capecitabine	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
Experimental: Arm 2D T-DXd, pembrolizumab and 5-FU or capecitabine	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/Vaccine: Pembrolizumab Pembrolizumab: administered as an IV infusion
Experimental: Arm 2E T-DXd and pembrolizumab	Drug: Trastuzumab deruxtecan T-DXd: administered as an IV infusion Other Name: DS-8201a Biological/Vaccine: Pembrolizumab Pembrolizumab: administered as an IV infusion
Experimental: Arm 2F T-DXd, pembrolizumab and 5-FU or capecitabine	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/Vaccine: Pembrolizumab Pembrolizumab: administered as an IV infusion
Experimental: Arm 3A T-DXd, Volrustomig and 5-FU or capecitabine	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/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: MEDI5752
Experimental: Arm 3B T-DXd, Volrustomig and 5-FU or capecitabine	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/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: MEDI5752
Experimental: Arm 4A T-DXd, Rilvegostomig and 5-FU or capecitabine	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/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: AZD2936
Experimental: Arm 4B T-DXd, Rilvegostomig and 5-FU or capecitabine	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/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: AZD2936

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]