Japanease

Nov. 17, 2020

Dec. 15, 2020

jRCT2031200203

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)

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

Nagao Kiminori

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Nov. 18, 2020

210

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

Brazil/Canada/Germany/Italy/Korea/Netherlands/Poland/Spain/Taiwan/ United States

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.

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.

18age old over
130age old under

Both

Gastric Cancer

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: 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
T-DXd and 5-FU or capecitabine and 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

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 1E
T-DXd, durvalumab and 5-FU or capecitabine
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Biological: 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/capecitabine, and cisplatin/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: 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, and 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

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

Experimental: Arm 2D
T-DXd, 5-FU or capecitabine, and durvalumab
Drug: Fluorouracil (5-FU)
5-FU: administered as an IV infusion

Drug: Capecitabine
Capecitabine: administered orally

Biological: Durvalumab
Durvalumab: administered as an IV infusion
Other Name: MEDI4736

Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a

1. 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. ]
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

2. Part 2: Objective Response Rate (ORR) [ Time Frame: 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.

1. Part 1: Objective Response Rate (ORR) [ Time Frame: 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: Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Safety will be assessed for approximately 24 months from informed consent. ]
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

3. Duration of Response (DoR) [ Time Frame: An average of approximately 18 months. ]
DOR is defined as the time from the date of first documented response until the date of documented progression or death

4. Disease Control Rate (DCR) [ Time Frame: An average of approximately 18 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)

5. Progression Free Survival (PFS) [ Time Frame: An average of approximately 18 months. ]
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

6. Overall survival (OS) [ Time Frame: An average of approximately 30 months. ]
OS is the time from date of treatment assignment (Part 1) or date of randomization (Part 2) until death due to any cause

7. Serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181a in all arms [ Time Frame: An average of 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

8. Serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab [ Time Frame: An average of approximately 24 months. ]
Individual participant data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab.

9. Presence of ADAs for T-DXd and durvalumab (in study arms including T-DXd and durvalumab) [ Time Frame: An average of 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.

Pending

DAIICHI SANKYO Co.,Ltd.
AstraZeneca
Applicable
National Cancer Ctr IRB#2-j
5-1-1 Tsukiji, Chuo-ku, Tokyo

+81-3-3542-2511

Chiken_CT@ml.res.ncc.go.jp
Approval

Nov. 04, 2020

Yes

Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Supporting Materials: Informed Consent Form (ICF) Time Frame: Study start to completion date Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

NCT04379596
ClinicalTrials.gov