DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]

NCT03329690 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: DS8201-A-J202173727DESTINY-G01
• Study Type: interventional
• Target: 233
• Locations: 2 countries
• Sites: 66

Brief Summary

The primary purpose of this trial is to compare the efficacy and safety of DS-8201a and physician's choice treatment in HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma patients who have progressed on two prior treatment regimens including fluoropyrimidine agent, platinum agent, and trastuzumab.

Conditions

Neoplasm, Gastrointestinal

Keywords

Adenocarcinoma Metastatic; Adenocarcinoma of the Stomach; Adenocarcinoma of the Gastroesophageal Junction; HER2 Overexpression; Adenocarcinoma, Locally Advanced; DESTINY - Gastric 01

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

  The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported.

  Baseline to date of first documented objective response (CR or PR), up to 36 months postdose

• Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

  The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on RECIST version 1.1. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported.

  Baseline to date of first documented objective response, up to 36 months postdose

Secondary Outcomes (15)

• Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

  From the date of randomization to the date of death (due to any cause), up to 36 months postdose

• Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

  From the date of randomization to the first documented disease progression or date of death (whichever occurs first), up to 36 months postdose

• Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)

  From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 36 months postdose

• Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

  Baseline to date of first documented objective response (CR, PR, and SD), up to 36 months postdose

• Objective Response Rate and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)

  From randomization to first documented objective response, up to 36 months postdose

Study Arms (4)

Parallel: DS-8201a

EXPERIMENTAL

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive DS-8201a once every 3 weeks.

Drug: DS-8201a

Parallel: Physician's Choice

ACTIVE COMPARATOR

Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive monotherapy prescribed by the physician before enrollment.

Drug: Physician's Choice

Exploratory: Naïve HER2 IHC 2+/ISH-

OTHER

A maximum of 20 non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every three weeks.

Drug: DS-8201a

Exploratory: Naïve HER2 IHC 1+

OTHER

A maximum of 20 non-randomized patients with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every 3 weeks.

Drug: DS-8201a

Interventions

DS-8201a DRUG

DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.

Also known as: Experimental product

Exploratory: Naïve HER2 IHC 1+; Exploratory: Naïve HER2 IHC 2+/ISH-; Parallel: DS-8201a

Physician's Choice DRUG

Either: Irinotecan monotherapy (Starting dosage and usage is 150 mg/m2 biweekly, with dose reduction permitted) Paclitaxel monotherapy (Starting dosage and usage is 80 mg/m2 weekly, with dose reduction permitted)

Also known as: Standard of Care

Parallel: Physician's Choice

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction
• Progression on and after at least 2 prior regimens
• Has an adequate tumor sample
• Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

You may not qualify if:

• Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
• Has a QTc prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females
• Has a medical history of clinically significant lung disease
• Is suspected to have certain other protocol-defined diseases based on imaging at screening period
• Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
• safety or well-being of the participant or offspring
• safety of study staff
• analysis of results

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead
• AstraZeneca: collaborator

Study Sites (66)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

Hirosaki University Hospital

Hirosaki, Aomori, 036-8563, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

Japan Community Health Care Organization Kyushu Hospital

Kitakyushu, Fukuoka, 806-8501, Japan

Location

Gunma Prefectural Cancer Center

Ōta, Gunma, 373-8550, Japan

Location

Kure Medical Center

Kure, Hiroshima, 737-0023, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo Cancer Center

Akashi, Hyōgo, 673-8558, Japan

Location

Kansai Rosai Hospital

Amagasaki, Hyōgo, 660-8511, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

Ibaraki Prefectural Central Hospital

Kasama, Ibaraki, 309-1793, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Iwate Medical University Hospital

Shiwa-gun, Iwate, 028-3695, Japan

Location

Kagawa University Hospital

Kita, Kagawa-ken, 761-0793, Japan

Location

St. Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

The Kitasato Institute Kitasato University Hospital

Sagamihara, Kanagawa, 252-0375, Japan

Location

Yokohama City University Medical Center

Yokohama, Kanagawa, 232-0024, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Japanese Red Cross Kyoto Daini Hospital

Kamigyō-ku, Kyoto, 602-8026, Japan

Location

Miyagi Cancer Center

Natori-shi, Miyagi, 981-1293, Japan

Location

Osaki Citizen Hospital

Ōsaki, Miyagi, 989-6183, Japan

Location

Osaka University Hospital

Suita, Osaka, 565-0871, Japan

Location

Toyonaka Municipal Hospital

Toyonaka, Osaka, 560-8565, Japan

Location

Tochigi Cancer Center

Utsunomiya, Tochigi, 320-0834, Japan

Location

Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo, 113-8677, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-Ku, Tokyo, 135-8550, Japan

Location

Showa University Koto Toyosu Hospital

Koto-Ku, Tokyo, 135-8577, Japan

Location

Toranomon Hospital

Minato-Ku, Tokyo, 105-8470, Japan

Location

Chiba Cancer Center

Chiba, 260-8717, Japan

Location

Fukui Prefectural Hospital

Fukui, 910-8526, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Gifu University Hospital

Gifu, 501-1194, Japan

Location

Hiroshima City Asa Citizens Hospital

Hiroshima, 731-0293, Japan

Location

Hiroshima Prefectural Hospital

Hiroshima, 734-8530, Japan

Location

Kochi Health Sciences Center

Kochi, 781-8555, Japan

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital

Osaka, 534-0021, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Osaka General Medical Center

Osaka, 558-8558, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

Saitama Cancer Center

Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

Shizuoka General Hospital

Shizuoka, 420-8527, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

National Cancer Center

Ilsan, Gyeonggi-do, 10408, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Chonnam National University Hwasun Hospital

Gwangju, 58128, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Chonbuk National University Hospital

Jeonju, 54907, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Yonsei Cancer Center, Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Chung-Ang University Hospital

Seoul, 06973, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Related Publications (2)

• Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. doi: 10.1056/NEJMoa2004413. Epub 2020 May 29.

  PMID: 32469182 RESULT

• Yamaguchi K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Shimoyama T, Lee KW, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Shitara K. Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. J Clin Oncol. 2023 Feb 1;41(4):816-825. doi: 10.1200/JCO.22.00575. Epub 2022 Nov 15.

  PMID: 36379002 DERIVED

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Adenocarcinoma

Interventions

trastuzumab deruxtecan; Standard of Care

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two randomized investigative arms will run in parallel (DS-8201a and Physician's Choice), with participants who have disease progression after two previous regimens. Two non-randomized exploratory arms will run with HER2 treatment-naive participants.

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: November 2, 2017
• Primary Completion: November 8, 2019
• Study Completion: December 11, 2020
• Last Updated: March 18, 2022
• Results First Posted: November 27, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

JP (48); KR (18)