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

Sponsor
Daiichi Sankyo Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT03329690
Collaborator
AstraZeneca (Industry)
233
Enrollment
66
Locations
4
Arms
37.3
Actual Duration (Months)
3.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
233 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date :
Nov 2, 2017
Actual Primary Completion Date :
Nov 8, 2019
Actual Study Completion Date :
Dec 11, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Parallel: DS-8201a

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
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.
Other Names:
  • Experimental product

    		•
    Active Comparator: Parallel: Physician's Choice

    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
    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)
    Other Names:
  • Standard of Care

    		•
    Other: Exploratory: Naïve HER2 IHC 2+/ISH-

    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
    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.
    Other Names:
  • Experimental product

    		•
    Other: Exploratory: Naïve HER2 IHC 1+

    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
    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.
    Other Names:
  • Experimental product

    		•

    Outcome Measures

    Primary Outcome Measures

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

      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.

    2. 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) [Baseline to date of first documented objective response, up to 36 months postdose]

      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.

    Secondary Outcome Measures

    1. 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]

      Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.

    2. 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]

      Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.

    3. 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]

      Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only.

    4. 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]

      Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, 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 stable disease (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.

    5. 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]

      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 Review (ICR) based on RECIST version 1.1. 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 CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator 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 PD (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.

    6. Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set) [From date of randomization to first documentation of PD, death due to any cause, or treatment discontinuation (whichever comes first), up to 36 months postdose]

      Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.

    7. Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set) [From randomization to first documented objective response, up to 36 months postdose]

      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 Investigator based on RECIST version 1.1. 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 CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator 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 PD (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.

    8. Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a [Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)]

      Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.

    9. Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a [Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)]

      Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.

    10. Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a [Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)]

      Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.

    11. Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a [Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)]

      Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.

    12. Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a [Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)]

      Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.

    13. Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a [Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)]

      Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.

    14. Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set) [Baseline up to 47 days after last dose, up to 36 months postdose]

      A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.

    15. Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) ≥20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set) [Baseline up to 47 days after last dose, up to 36 months postdose]

      A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction

    2. Progression on and after at least 2 prior regimens

    3. Has an adequate tumor sample

    4. Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

    Exclusion Criteria:

    1. Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia

    2. Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females

    3. Has a medical history of clinically significant lung disease

    4. Is suspected to have certain other protocol-defined diseases based on imaging at screening period

    5. 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:

    6. safety or well-being of the participant or offspring

    7. safety of study staff

    8. analysis of results

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aichi Cancer Center Hospital Nagoya Aichi Japan 464-8681
    2 Hirosaki University Hospital Hirosaki Aomori Japan 036-8563
    3 National Cancer Center Hospital East Kashiwa Chiba Japan 277-8577
    4 National Hospital Organization Shikoku Cancer Center Matsuyama Ehime Japan 791-0280
    5 Japan Community Health Care Organization Kyushu Hospital Kitakyushu Fukuoka Japan 806-8501
    6 Gunma Prefectural Cancer Center Ōta Gunma Japan 373-8550
    7 Kure Medical Center Kure Hiroshima Japan 737-0023
    8 Hokkaido University Hospital Sapporo Hokkaido Japan 060-8648
    9 Hyogo Cancer Center Akashi Hyogo Japan 673-8558
    10 Kansai Rosai Hospital Amagasaki Hyogo Japan 660-8511
    11 Kobe City Medical Center General Hospital Kobe Hyogo Japan 650-0047
    12 Ibaraki Prefectural Central Hospital Kasama Ibaraki Japan 309-1793
    13 Kanazawa University Hospital Kanazawa Ishikawa Japan 920-8641
    14 Iwate Medical University Hospital Shiwa-gun Iwate Japan 028-3695
    15 Kagawa University Hospital Kita Kagawa Japan 761-0793
    16 St. Marianna University School of Medicine Hospital Kawasaki Kanagawa Japan 216-8511
    17 The Kitasato Institute Kitasato University Hospital Sagamihara Kanagawa Japan 252-0375
    18 Yokohama City University Medical Center Yokohama Kanagawa Japan 232-0024
    19 Kanagawa Cancer Center Yokohama Kanagawa Japan 241-8515
    20 Japanese Red Cross Kyoto Daini Hospital Kamigyō-ku Kyoto Japan 602-8026
    21 Miyagi Cancer Center Natori Miyagi Japan 981-1293
    22 Osaki Citizen Hospital Osaki Miyagi Japan 989-6183
    23 Osaka University Hospital Suita Osaka Japan 565-0871
    24 Toyonaka Municipal Hospital Toyonaka Osaka Japan 560-8565
    25 Tochigi Cancer Center Utsunomiya Tochigi Japan 320-0834
    26 Tokyo Metropolitan Komagome Hospital Bunkyō-Ku Tokyo Japan 113-8677
    27 National Cancer Center Hospital Chuo Ku Tokyo Japan 104-0045
    28 The Cancer Institute Hospital of Japanese Foundation for Cancer Research Koto-Ku Tokyo Japan 135-8550
    29 Showa University Koto Toyosu Hospital Koto-Ku Tokyo Japan 135-8577
    30 Toranomon Hospital Minato-Ku Tokyo Japan 105-8470
    31 Chiba Cancer Center Chiba Japan 260-8717
    32 Fukui Prefectural Hospital Fukui Japan 910-8526
    33 National Hospital Organization Kyushu Cancer Center Fukuoka Japan 811-1395
    34 Kyushu University Hospital Fukuoka Japan 812-8582
    35 Gifu University Hospital Gifu Japan 501-1194
    36 Hiroshima City Asa Citizens Hospital Hiroshima Japan 731-0293
    37 Hiroshima Prefectural Hospital Hiroshima Japan 734-8530
    38 Kochi Health Sciences Center Kochi Japan 781-8555
    39 Niigata Cancer Center Hospital Niigata Japan 951-8566
    40 Okayama University Hospital Okayama Japan 700-8558
    41 Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital Osaka Japan 534-0021
    42 Osaka International Cancer Institute Osaka Japan 541-8567
    43 Osaka General Medical Center Osaka Japan 558-8558
    44 Kindai University Hospital Osaka Japan 589-8511
    45 Saitama Cancer Center Saitama Japan 362-0806
    46 Shizuoka Cancer Center Shizuoka Japan 411-8777
    47 Shizuoka General Hospital Shizuoka Japan 420-8527
    48 Keio University Hospital Tokyo Japan 160-8582
    49 Chungbuk National University Hospital Cheongju-si Chungcheongbuk-do Korea, Republic of 28644
    50 National Cancer Center Ilsan Gyeonggi-do Korea, Republic of 10408
    51 Inje University Haeundae Paik Hospital Busan Korea, Republic of 48108
    52 Dong-A University Hospital Busan Korea, Republic of 49201
    53 Kyungpook National University Chilgok Hospital Daegu Korea, Republic of 41404
    54 Chonnam National University Hwasun Hospital Gwangju Korea, Republic of 58128
    55 Gachon University Gil Medical Center Incheon Korea, Republic of 21565
    56 Chonbuk National University Hospital Jeonju Korea, Republic of 54907
    57 Seoul National University Bundang Hospital Seongnam Korea, Republic of 13620
    58 Korea University Anam Hospital Seoul Korea, Republic of 02841
    59 Seoul National University Hospital Seoul Korea, Republic of 03080
    60 Yonsei Cancer Center, Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    61 Asan Medical Center Seoul Korea, Republic of 05505
    62 Gangnam Severance Hospital Seoul Korea, Republic of 06273
    63 Samsung Medical Center Seoul Korea, Republic of 06351
    64 The Catholic University of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 06591
    65 Chung-Ang University Hospital Seoul Korea, Republic of 06973
    66 Korea University Guro Hospital Seoul Korea, Republic of 08308

    Sponsors and Collaborators

    • Daiichi Sankyo Co., Ltd.
    • AstraZeneca

    Investigators

    • Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Daiichi Sankyo Co., Ltd.
    ClinicalTrials.gov Identifier:
    NCT03329690
    Other Study ID Numbers:
    • DS8201-A-J202
    • 173727
    • DESTINY-G01
    First Posted:
    Nov 6, 2017
    Last Update Posted:
    Mar 18, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Daiichi Sankyo Co., Ltd.
    Adenocarcinoma Metastatic
    Adenocarcinoma of the Stomach
    Adenocarcinoma of the Gastroesophageal Junction
    HER2 Overexpression
    Adenocarcinoma, Locally Advanced
    DESTINY - Gastric 01
    Additional relevant MeSH terms:
    Adenocarcinoma
    Gastrointestinal Neoplasms
    Digestive System Neoplasms

    Study Results

    Participant Flow

    Recruitment Details In the Primary Cohort, a total of 188 participants who met all inclusion criteria and no exclusion criteria were enrolled and randomized to treatment. In the Exploratory Cohorts, a total of 45 non-randomized participants were enrolled and 44 patients received treatment. Study participants for all cohorts were enrolled at clinic sites in South Korea and Japan. Participants took part of the study from November 2, 2017 to Data Cut-Off (DCO) date of December 11, 2020.
    Pre-assignment Detail In the Primary Cohort, participants with HER2 overexpressing gastric of GEJ adenocarcinoma were randomized (2:1) to either DS-8201a or physician's choice (irinotecan or paclitaxel). In the Exploratory Cohorts, participants with HER2 IHC 2+/ISH negative advanced gastric or GEJ adenocarcinoma who were naïve to HER2 treatment received DS-8201a.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Period Title: Overall Study
    STARTED 126 55 7 21 24
    Received Treatment 125 55 7 20 24
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 126 55 7 21 24

    Baseline Characteristics

    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a Total
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks. Total of all reporting groups
    Overall Participants 125 55 7 20 24 231
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    55
    44%
    24
    43.6%
    3
    42.9%
    11
    55%
    17
    70.8%
    110
    47.6%
    >=65 years
    70
    56%
    31
    56.4%
    4
    57.1%
    9
    45%
    7
    29.2%
    121
    52.4%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.2
    (10.36)
    64.9
    (10.54)
    63.4
    (8.96)
    62.5
    (10.87)
    55.5
    (12.12)
    63.3
    (10.86)
    Sex: Female, Male (Count of Participants)
    Female
    30
    24%
    13
    23.6%
    2
    28.6%
    4
    20%
    7
    29.2%
    56
    24.2%
    Male
    95
    76%
    42
    76.4%
    5
    71.4%
    16
    80%
    17
    70.8%
    175
    75.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    125
    100%
    55
    100%
    7
    100%
    20
    100%
    24
    100%
    231
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    South Korea
    26
    20.8%
    11
    20%
    1
    14.3%
    4
    20%
    5
    20.8%
    47
    20.3%
    Japan
    99
    79.2%
    44
    80%
    6
    85.7%
    16
    80%
    19
    79.2%
    184
    79.7%

    Outcome Measures

    1. Primary Outcome
    Title 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)
    Description 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.
    Time Frame Baseline to date of first documented objective response (CR or PR), up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Objective response rate was assessed in the Primary Cohort in the Intent-to-Treat Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment.
    Measure Participants 126 55 7 62
    Unconfirmed ORR, 25 months (DCO: Nov 8, 2019)
    61
    48.8%
    7
    12.7%
    1
    14.3%
    8
    40%
    Unconfirmed ORR, 36 months (DCO: Dec 11, 2020)
    61
    48.8%
    7
    12.7%
    1
    14.3%
    8
    40%
    Confirmed ORR, 25 months (DCO: Nov 8, 2019)
    51
    40.8%
    6
    10.9%
    1
    14.3%
    7
    35%
    Confirmed ORR, 36 months (DCO: Dec 11, 2020)
    50
    40%
    6
    10.9%
    1
    14.3%
    7
    35%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection DS-8201a, Physician's Choice Overall
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments CMH test with region as a stratification factor
    2. Primary Outcome
    Title 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)
    Description 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.
    Time Frame Baseline to date of first documented objective response, up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Best overall response was assessed in the Primary Cohort in the Intent-to-Treat Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment.
    Measure Participants 126 55 7 62
    Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)
    11
    8.8%
    0
    0%
    0
    0%
    0
    0%
    Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)
    10
    8%
    0
    0%
    0
    0%
    0
    0%
    Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)
    50
    40%
    7
    12.7%
    1
    14.3%
    8
    40%
    Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)
    51
    40.8%
    7
    12.7%
    1
    14.3%
    8
    40%
    Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)
    46
    36.8%
    27
    49.1%
    3
    42.9%
    30
    150%
    Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)
    47
    37.6%
    27
    49.1%
    3
    42.9%
    30
    150%
    Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)
    15
    12%
    18
    32.7%
    0
    0%
    18
    90%
    Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)
    15
    12%
    18
    32.7%
    0
    0%
    18
    90%
    Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)
    4
    3.2%
    3
    5.5%
    3
    42.9%
    6
    30%
    Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)
    3
    2.4%
    3
    5.5%
    3
    42.9%
    6
    30%
    Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)
    10
    8%
    0
    0%
    0
    0%
    0
    0%
    Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)
    9
    7.2%
    0
    0%
    0
    0%
    0
    0%
    Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)
    41
    32.8%
    6
    10.9%
    1
    14.3%
    7
    35%
    Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)
    41
    32.8%
    6
    10.9%
    1
    14.3%
    7
    35%
    Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)
    55
    44%
    28
    50.9%
    3
    42.9%
    31
    155%
    Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)
    57
    45.6%
    28
    50.9%
    3
    42.9%
    31
    155%
    Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)
    15
    12%
    18
    32.7%
    0
    0%
    18
    90%
    Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)
    15
    12%
    18
    32.7%
    0
    0%
    18
    90%
    Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)
    5
    4%
    3
    5.5%
    3
    42.9%
    6
    30%
    Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)
    4
    3.2%
    3
    5.5%
    3
    42.9%
    6
    30%
    3. Secondary Outcome
    Title Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
    Description Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.
    Time Frame From the date of randomization to the date of death (due to any cause), up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Duration of survival and overall survival were assessed in the Intent-to-Treat Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 126 55 7 62 21 22
    Duration of survival follow up, 25 months (DCO: Nov 8, 2019)
    8.0
    7.1
    5.5
    7.0
    7.3
    8.4
    Duration of survival follow up, 36 months (DCO: Dec 11, 2020)
    12.3
    8.4
    14.3
    8.5
    7.3
    8.5
    Overall survival, 25 months (DCO: Nov 8, 2019)
    12.5
    8.4
    14.3
    8.4
    7.8
    8.5
    Overall survival, 36 months (DCO: Dec 11, 2020)
    12.6
    8.6
    14.3
    8.9
    7.8
    8.5
    4. Secondary Outcome
    Title 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)
    Description Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
    Time Frame From the date of randomization to the first documented disease progression or date of death (whichever occurs first), up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Progression-free survival (PFS) was assessed in the Intent-to-Treat Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 126 55 7 62 21 22
    PFS, 25 months (DCO: Nov 8, 2019)
    5.6
    2.8
    4.9
    3.5
    4.4
    2.8
    PFS, 36 months (DCO: Dec 11, 2020)
    5.6
    2.8
    4.9
    3.5
    4.4
    2.8
    5. Secondary Outcome
    Title 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)
    Description Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    Duration of response (DOR) was assessed in the Full Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 61 7 1 8 7 4
    Unconfirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019)
    8.4
    4.1
    3.9
    3.9
    6.8
    7.1
    Unconfirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020)
    11.3
    4.1
    3.9
    3.9
    6.8
    5.8
    Confirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019)
    11.3
    4.1
    3.9
    3.9
    7.6
    12.5
    Confirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020)
    12.7
    4.1
    3.9
    3.9
    7.6
    11.2
    6. Secondary Outcome
    Title 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)
    Description Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, 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 stable disease (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.
    Time Frame Baseline to date of first documented objective response (CR, PR, and SD), up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Disease control rate (DCR) was assessed in the Intent-to-Treat Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 126 55 7 62 21 22
    DCR, 25 months (DCO: Nov 8, 2019)
    107
    85.6%
    34
    61.8%
    4
    57.1%
    38
    190%
    17
    70.8%
    15
    6.5%
    DCR, 36 months (DCO: Dec 11, 2020)
    108
    86.4%
    34
    61.8%
    4
    57.1%
    38
    190%
    17
    70.8%
    15
    6.5%
    7. Secondary Outcome
    Title 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)
    Description 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 Review (ICR) based on RECIST version 1.1. 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 CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator 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 PD (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.
    Time Frame From randomization to first documented objective response, up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Best overall response was assessed in the Exploratory Cohorts in the Intent-to-Treat Analysis Set.
    Arm/Group Title Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 21 22
    Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)
    5
    4%
    2
    3.6%
    Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)
    5
    4%
    2
    3.6%
    Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)
    0
    0%
    0
    0%
    Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)
    0
    0%
    0
    0%
    Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)
    5
    4%
    2
    3.6%
    Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)
    5
    4%
    2
    3.6%
    Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)
    12
    9.6%
    13
    23.6%
    Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)
    12
    9.6%
    13
    23.6%
    Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)
    3
    2.4%
    6
    10.9%
    Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)
    3
    2.4%
    6
    10.9%
    Inevaluable, 25 months (DCO: Nov 8, 2019)
    1
    0.8%
    1
    1.8%
    Inevaluable, 36 months (DCO: Dec 11, 2020)
    1
    0.8%
    1
    1.8%
    8. Secondary Outcome
    Title Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
    Description Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.
    Time Frame From date of randomization to first documentation of PD, death due to any cause, or treatment discontinuation (whichever comes first), up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Time to treatment failure (TTF) was assessed in the Full Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 55 7 62 20 22
    TTF, 25 months (DCO: Nov 8, 2019)
    4.2
    2.6
    2.9
    2.6
    3.7
    2.2
    TTF, 36 months (DCO: Dec 11, 2020)
    4.3
    2.6
    2.9
    2.6
    3.7
    2.2
    9. Secondary Outcome
    Title Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set)
    Description 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 Investigator based on RECIST version 1.1. 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 CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator 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 PD (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.
    Time Frame From randomization to first documented objective response, up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Objective response rate (ORR) and best overall response (BOR) were assessed in the Response Evaluable Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 119 51 5 56 19 21
    Unconfirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)
    60
    48%
    7
    12.7%
    1
    14.3%
    8
    40%
    10
    41.7%
    5
    2.2%
    Unconfirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)
    60
    48%
    7
    12.7%
    1
    14.3%
    8
    40%
    10
    41.7%
    5
    2.2%
    Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)
    4
    3.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)
    4
    3.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)
    56
    44.8%
    7
    12.7%
    1
    14.3%
    8
    40%
    10
    41.7%
    5
    2.2%
    Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)
    56
    44.8%
    7
    12.7%
    1
    14.3%
    8
    40%
    10
    41.7%
    5
    2.2%
    Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)
    42
    33.6%
    27
    49.1%
    1
    14.3%
    28
    140%
    7
    29.2%
    8
    3.5%
    Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)
    42
    33.6%
    27
    49.1%
    1
    14.3%
    28
    140%
    7
    29.2%
    8
    3.5%
    Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)
    15
    12%
    15
    27.3%
    2
    28.6%
    17
    85%
    2
    8.3%
    8
    3.5%
    Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)
    15
    12%
    15
    27.3%
    2
    28.6%
    17
    85%
    2
    8.3%
    8
    3.5%
    Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)
    2
    1.6%
    2
    3.6%
    1
    14.3%
    3
    15%
    0
    0%
    0
    0%
    Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)
    2
    1.6%
    2
    3.6%
    1
    14.3%
    3
    15%
    0
    0%
    0
    0%
    Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)
    49
    39.2%
    5
    9.1%
    1
    14.3%
    6
    30%
    8
    33.3%
    3
    1.3%
    Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)
    51
    40.8%
    5
    9.1%
    1
    14.3%
    6
    30%
    8
    33.3%
    3
    1.3%
    Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)
    3
    2.4%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)
    4
    3.2%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)
    46
    36.8%
    5
    9.1%
    1
    14.3%
    6
    30%
    8
    33.3%
    3
    1.3%
    Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)
    47
    37.6%
    5
    9.1%
    1
    14.3%
    6
    30%
    8
    33.3%
    3
    1.3%
    Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)
    53
    42.4%
    28
    50.9%
    1
    14.3%
    29
    145%
    9
    37.5%
    10
    4.3%
    Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)
    51
    40.8%
    28
    50.9%
    1
    14.3%
    29
    145%
    9
    37.5%
    10
    4.3%
    Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)
    15
    12%
    16
    29.1%
    2
    28.6%
    18
    90%
    2
    8.3%
    8
    3.5%
    Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)
    15
    12%
    16
    29.1%
    2
    28.6%
    18
    90%
    2
    8.3%
    8
    3.5%
    Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)
    2
    1.6%
    2
    3.6%
    1
    14.3%
    3
    15%
    0
    0%
    0
    0%
    Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)
    2
    1.6%
    2
    3.6%
    1
    14.3%
    3
    15%
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
    Description Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
    Time Frame Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
    Arm/Group Title DS-8201a Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 20 24
    Cmax: DS-8201a, Cycle 1
    127
    (28.4)
    119
    (29.1)
    127
    (24.5)
    Cmax: DS-8201a, Cycle 3
    137
    (31.1)
    128
    (25.6)
    123
    (23.2)
    Cmax: Total Anti-HER2 antibody, Cycle 1
    116
    (30.6)
    105
    (26.1)
    110
    (19.6)
    Cmax: Total Anti-HER2 antibody, Cycle 3
    121
    (28.4)
    115
    (24.2)
    112
    (21.9)
    Ctrough: DS-8201a, Cycle 1
    5.56
    (3.08)
    4.52
    (2.42)
    9.51
    (23.4)
    Ctrough: DS-8201a, Cycle 3
    13.4
    (17.3)
    8.84
    (3.09)
    13.2
    (18.6)
    Ctrough: Total Anti-HER2 antibody, Cycle 1
    8.56
    (8.60)
    5.33
    (2.97)
    10.0
    (20.5)
    Ctrough: Total Anti-HER2 antibody, Cycle 3
    15.6
    (13.6)
    12.2
    (5.76)
    14.6
    (17.6)
    11. Secondary Outcome
    Title Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a
    Description Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
    Time Frame Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
    Arm/Group Title DS-8201a Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 20 24
    Cmax: MAAA-1181a, Cycle 1
    12.1
    (4.79)
    13.3
    (8.52)
    13.3
    (7.37)
    Cmax: MAAA-1181a, Cycle 3
    9.08
    (3.81)
    7.62
    (1.86)
    9.83
    (3.75)
    Ctrough: MAAA-1181a, Cycle 1
    0.316
    (0.294)
    0.290
    (0.237)
    0.772
    (2.28)
    Ctrough: MAAA-1181a Cycle 3
    0.714
    (2.19)
    0.378
    (0.138)
    1.10
    (1.95)
    12. Secondary Outcome
    Title Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
    Description Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
    Time Frame Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. No patient samples were collected or analyzed for AUClast DS-8201a and total anti-HER2 antibody for Cycle 3 as AUClast was planned to be assessed only for Cycle 1.
    Arm/Group Title DS-8201a Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 20 24
    AUClast: DS-8201a, Cycle 1
    611
    (150)
    572
    (143)
    545
    (160)
    AUClast: Total Anti-HER2 antibody, Cycle 1
    667
    (241)
    570
    (126)
    547
    (167)
    AUC21d: DS-8201a, Cycle 1
    612
    (150)
    572
    (143)
    569
    (114)
    AUC21d: DS-8201a, Cycle 3
    867
    (213)
    746
    (197)
    724
    (71.9)
    AUC21d: Total Anti-HER2 antibody, Cycle 1
    651
    (210)
    570
    (126)
    582
    (104)
    AUC21d: Total Anti-HER2 antibody, Cycle 3
    888
    (244)
    775
    (210)
    737
    (110)
    13. Secondary Outcome
    Title Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a
    Description Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
    Time Frame Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. No patient samples were collected or analyzed for MAAA-1181a for Cycle 3 as AUClast was planned to be assessed only for Cycle 1.
    Arm/Group Title DS-8201a Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 20 24
    AUClast: MAAA-1181a, Cycle 1
    46.7
    (16.3)
    53.4
    (42.7)
    44.5
    (22.5)
    AUC21d: MAAA-1181a, Cycle 1
    46.4
    (16.1)
    44.9
    (20.1)
    44.5
    (22.5)
    AUC21d: MAAA-1181a, Cycle 3
    42.0
    (15.1)
    39.4
    (8.36)
    44.6
    (17.8)
    14. Secondary Outcome
    Title Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
    Description Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
    Time Frame Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
    Arm/Group Title DS-8201a Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 20 24
    DS-8201a, Cycle 1
    3.93
    3.90
    3.89
    DS-8201a, Cycle 3
    4.00
    4.00
    4.00
    Total Anti-HER2 antibody, Cycle 1
    3.83
    3.83
    3.87
    Total Anti-HER2 antibody, Cycle 3
    3.98
    4.00
    3.75
    MAAA-1181a, Cycle 1
    6.85
    6.83
    6.81
    MAAA-1181a, Cycle 3
    6.80
    6.82
    6.77
    15. Secondary Outcome
    Title Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
    Description Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
    Time Frame Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in patients with available data in the Pharmacokinetic Analysis Set.
    Arm/Group Title DS-8201a Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 124 20 23
    DS-8201a, Cycle 1
    5.77
    (1.37)
    5.54
    (1.08)
    5.52
    (1.17)
    DS-8201a, Cycle 3
    7.46
    (1.82)
    6.40
    (1.00)
    6.35
    (1.73)
    Total Anti-HER2 antibody, Cycle 1
    6.20
    (2.22)
    5.54
    (1.01)
    5.65
    (1.51)
    Total Anti-HER2 antibody, Cycle 3
    8.00
    (2.04)
    7.90
    (2.10)
    6.17
    (1.15)
    MAAA-1181a, Cycle 1
    5.50
    (1.11)
    5.21
    (0.939)
    5.61
    (1.19)
    MAAA-1181a, Cycle 3
    7.01
    (1.65)
    6.18
    (1.02)
    5.80
    (1.10)
    16. Secondary Outcome
    Title Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set)
    Description A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.
    Time Frame Baseline up to 47 days after last dose, up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Adverse events were assessed in the Safety Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 55 7 62 20 24
    Any TEAE, 25 months (DCO: Nov 8, 2019)
    125
    100%
    54
    98.2%
    7
    100%
    61
    305%
    20
    83.3%
    24
    10.4%
    Any TEAE, 36 months (DCO: Dec 11, 2020)
    125
    100%
    54
    98.2%
    7
    100%
    61
    305%
    20
    83.3%
    24
    10.4%
    Drug-related TEAEs, 25 months (DCO: Nov 8, 2019)
    122
    97.6%
    51
    92.7%
    5
    71.4%
    56
    280%
    19
    79.2%
    24
    10.4%
    Drug-related TEAEs, 36 months (DCO: Dec 11, 2020)
    122
    97.6%
    51
    92.7%
    5
    71.4%
    56
    280%
    19
    79.2%
    24
    10.4%
    Serious TEAEs, 25 months (DCO: Nov 8, 2019)
    55
    44%
    14
    25.5%
    1
    14.3%
    15
    75%
    6
    25%
    11
    4.8%
    Serious TEAEs, 36 months (DCO: Dec 11, 2020)
    58
    46.4%
    15
    27.3%
    1
    14.3%
    16
    80%
    6
    25%
    11
    4.8%
    Drug-related serious TEAEs, 25 months (DCO: Nov 8, 2019)
    27
    21.6%
    5
    9.1%
    0
    0%
    5
    25%
    1
    4.2%
    6
    2.6%
    Drug-related serious TEAEs, 36 months (DCO: Dec 11, 2020)
    31
    24.8%
    5
    9.1%
    0
    0%
    5
    25%
    1
    4.2%
    6
    2.6%
    TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019)
    19
    15.2%
    4
    7.3%
    0
    0%
    4
    20%
    2
    8.3%
    1
    0.4%
    TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020)
    23
    18.4%
    4
    7.3%
    0
    0%
    4
    20%
    2
    8.3%
    1
    0.4%
    Drug-related TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019)
    12
    9.6%
    3
    5.5%
    0
    0%
    3
    15%
    1
    4.2%
    0
    0%
    Drug-related TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020)
    15
    12%
    3
    5.5%
    0
    0%
    3
    15%
    1
    4.2%
    0
    0%
    TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019)
    40
    32%
    21
    38.2%
    0
    0%
    21
    105%
    6
    25%
    8
    3.5%
    TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020)
    40
    32%
    21
    38.2%
    0
    0%
    21
    105%
    6
    25%
    8
    3.5%
    Drug-related TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019)
    38
    30.4%
    21
    38.2%
    0
    0%
    21
    105%
    6
    25%
    7
    3%
    Drug-related TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020)
    38
    30.4%
    21
    38.2%
    0
    0%
    21
    105%
    6
    25%
    7
    3%
    TEAEs associated with drug interrupted, 25 months (DCO: Nov 8, 2019)
    78
    62.4%
    20
    36.4%
    3
    42.9%
    23
    115%
    8
    33.3%
    10
    4.3%
    TEAEs associated with drug interrupted, 36 months (DCO: Dec 11, 2020)
    79
    63.2%
    20
    36.4%
    3
    42.9%
    23
    115%
    8
    33.3%
    10
    4.3%
    Drug-related TEAE associated with drug interrupted, 25 months (DCO: Nov 8, 2019)
    64
    51.2%
    17
    30.9%
    2
    28.6%
    19
    95%
    7
    29.2%
    10
    4.3%
    Drug-related TEAE associated with drug interrupted, 36 months (DCO: Dec 11, 2020)
    65
    52%
    17
    30.9%
    2
    28.6%
    19
    95%
    7
    29.2%
    10
    4.3%
    TEAEs associated with death, 25 months (DCO: Nov 8, 2019)
    8
    6.4%
    1
    1.8%
    1
    14.3%
    2
    10%
    2
    8.3%
    0
    0%
    TEAEs associated with death, 36 months (DCO: Dec 11, 2020)
    9
    7.2%
    1
    1.8%
    1
    14.3%
    2
    10%
    2
    8.3%
    0
    0%
    17. Secondary Outcome
    Title Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) ≥20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set)
    Description A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
    Time Frame Baseline up to 47 days after last dose, up to 36 months postdose

    Outcome Measure Data

    Analysis Population Description
    Adverse events were assessed in the Safety Analysis Set.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    Measure Participants 125 55 7 62 20 24
    Any TEAE, 25 months (DCO: Nov 8, 2019)
    125
    100%
    54
    98.2%
    7
    100%
    61
    305%
    20
    83.3%
    24
    10.4%
    Any TEAE, 36 months (DCO: Dec 11, 2020)
    125
    100%
    54
    98.2%
    7
    100%
    61
    305%
    20
    83.3%
    24
    10.4%
    Nausea, 25 months (DCO: Nov 8, 2019)
    79
    63.2%
    27
    49.1%
    2
    28.6%
    29
    145%
    11
    45.8%
    19
    8.2%
    Nausea, 36 months (DCO: Dec 11, 2020)
    79
    63.2%
    27
    49.1%
    2
    28.6%
    29
    145%
    11
    45.8%
    19
    8.2%
    Decreased appetite, 25 months (DCO: Nov 8, 2019)
    75
    60%
    27
    49.1%
    1
    14.3%
    28
    140%
    13
    54.2%
    18
    7.8%
    Decreased appetite, 36 months (DCO: Dec 11, 2020)
    76
    60.8%
    27
    49.1%
    1
    14.3%
    28
    140%
    13
    54.2%
    18
    7.8%
    Neutrophil count decreased, 25 months (DCO: Nov 8, 2019)
    77
    61.6%
    18
    32.7%
    3
    42.9%
    21
    105%
    8
    33.3%
    12
    5.2%
    Neutrophil count decreased, 36 months (DCO: Dec 11, 2020)
    79
    63.2%
    18
    32.7%
    3
    42.9%
    21
    105%
    8
    33.3%
    12
    5.2%
    Anaemia, 25 months (DCO: Nov 8, 2019)
    71
    56.8%
    17
    30.9%
    2
    28.6%
    19
    95%
    10
    41.7%
    10
    4.3%
    Anaemia, 36 months (DCO: Dec 11, 2020)
    71
    56.8%
    17
    30.9%
    2
    28.6%
    19
    95%
    10
    41.7%
    11
    4.8%
    White blood cell count decreased, 25 months (DCO: Nov 8, 2019)
    47
    37.6%
    18
    32.7%
    3
    42.9%
    21
    105%
    4
    16.7%
    7
    3%
    White blood cell count decreased, 36 months (DCO: Dec 11, 2020)
    49
    39.2%
    18
    32.7%
    3
    42.9%
    21
    105%
    4
    16.7%
    7
    3%
    Platelet count decreased, 25 months (DCO: Nov 8, 2019)
    47
    37.6%
    4
    7.3%
    0
    0%
    4
    20%
    3
    12.5%
    7
    3%
    Platelet count decreased, 36 months (DCO: Dec 11, 2020)
    48
    38.4%
    4
    7.3%
    0
    0%
    4
    20%
    3
    12.5%
    7
    3%
    Malaise, 25 months (DCO: Nov 8, 2019)
    43
    34.4%
    9
    16.4%
    1
    14.3%
    10
    50%
    4
    16.7%
    9
    3.9%
    Malaise, 36 months (DCO: Dec 11, 2020)
    44
    35.2%
    9
    16.4%
    1
    14.3%
    10
    50%
    4
    16.7%
    9
    3.9%
    Diarrhoea, 25 months (DCO: Nov 8, 2019)
    40
    32%
    20
    36.4%
    0
    0%
    20
    100%
    6
    25%
    8
    3.5%
    Diarrhoea, 36 months (DCO: Dec 11, 2020)
    41
    32.8%
    20
    36.4%
    0
    0%
    20
    100%
    6
    25%
    8
    3.5%
    Vomiting, 25 months (DCO: Nov 8, 2019)
    33
    26.4%
    5
    9.1%
    0
    0%
    5
    25%
    4
    16.7%
    7
    3%
    Vomiting, 36 months (DCO: Dec 11, 2020)
    33
    26.4%
    5
    9.1%
    0
    0%
    5
    25%
    4
    16.7%
    7
    3%
    Constipation, 25 months (DCO: Nov 8, 2019)
    30
    24%
    13
    23.6%
    1
    14.3%
    14
    70%
    5
    20.8%
    5
    2.2%
    Constipation, 36 months (DCO: Dec 11, 2020)
    31
    24.8%
    13
    23.6%
    2
    28.6%
    15
    75%
    5
    20.8%
    5
    2.2%
    Pyrexia, 25 months (DCO: Nov 8, 2019)
    30
    24%
    8
    14.5%
    2
    28.6%
    10
    50%
    3
    12.5%
    6
    2.6%
    Pyrexia, 36 months (DCO: Dec 11, 2020)
    31
    24.8%
    8
    14.5%
    2
    28.6%
    10
    50%
    3
    12.5%
    6
    2.6%
    Fatigue, 25 months (DCO: Nov 8, 2019)
    27
    21.6%
    15
    27.3%
    0
    0%
    15
    75%
    5
    20.8%
    6
    2.6%
    Fatigue, 36 months (DCO: Dec 11, 2020)
    27
    21.6%
    15
    27.3%
    0
    0%
    15
    75%
    5
    20.8%
    6
    2.6%
    Alopecia, 25 months (DCO: Nov 8, 2019)
    28
    22.4%
    8
    14.5%
    1
    14.3%
    9
    45%
    3
    12.5%
    1
    0.4%
    Alopecia, 36 months (DCO: Dec 11, 2020)
    28
    22.4%
    8
    14.5%
    1
    14.3%
    9
    45%
    3
    12.5%
    1
    0.4%
    Lymphocyte count decreased, 25 months (DCO: Nov 8, 2019)
    27
    21.6%
    2
    3.6%
    0
    0%
    2
    10%
    1
    4.2%
    3
    1.3%
    Lymphocyte count decreased, 36 months (DCO: Dec 11, 2020)
    30
    24%
    2
    3.6%
    0
    0%
    2
    10%
    1
    4.2%
    3
    1.3%
    Weight decreased, 25 months (DCO: Nov 8, 2019)
    17
    13.6%
    5
    9.1%
    0
    0%
    5
    25%
    4
    16.7%
    7
    3%
    Weight decreased, 36 months (DCO: Dec 11, 2020)
    19
    15.2%
    5
    9.1%
    0
    0%
    5
    25%
    4
    16.7%
    7
    3%
    Hypoalbuminaemia, 25 months (DCO: Nov 8, 2019)
    18
    14.4%
    7
    12.7%
    1
    14.3%
    8
    40%
    2
    8.3%
    5
    2.2%
    Hypoalbuminaemia, 36 months (DCO: Dec 11, 2020)
    18
    14.4%
    7
    12.7%
    1
    14.3%
    8
    40%
    2
    8.3%
    5
    2.2%
    Oedema peripheral, 25 months (DCO: Nov 8, 2019)
    13
    10.4%
    0
    0%
    0
    0%
    0
    0%
    4
    16.7%
    1
    0.4%
    Oedema peripheral, 36 months (DCO: Dec 11, 2020)
    15
    12%
    0
    0%
    0
    0%
    0
    0%
    4
    16.7%
    2
    0.9%
    Dysgeusia, 25 months (DCO: Nov 8, 2019)
    9
    7.2%
    4
    7.3%
    0
    0%
    4
    20%
    4
    16.7%
    1
    0.4%
    Dysgeusia, 36 months (DCO: Dec 11, 2020)
    9
    7.2%
    4
    7.3%
    0
    0%
    4
    20%
    4
    16.7%
    1
    0.4%
    Peripheral sensory neuropathy, 25 months (DCO: Nov 8, 2019)
    4
    3.2%
    0
    0%
    2
    28.6%
    2
    10%
    2
    8.3%
    0
    0%
    Peripheral sensory neuropathy, 36 months (DCO: Dec 11, 2020)
    4
    3.2%
    0
    0%
    2
    28.6%
    2
    10%
    2
    8.3%
    0
    0%

    Adverse Events

    Time Frame Treatment-emergent adverse event (TEAE) data were collected from baseline up to 47 days after last dose, up to 36 months postdose.
    Adverse Event Reporting Description A TEAE is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.
    Arm/Group Title DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Arm/Group Description Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive DS-8201a once every 3 weeks. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive irinotecan monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive paclitaxel monotherapy as prescribed by the physician before enrollment. Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease had progressed on two prior regimens, were randomized to receive either irinotecan or paclitaxel monotherapy as prescribed by the physician before enrollment. Non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every three weeks. Non-randomized participants with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma who received DS-8201a once every 3 weeks.
    All Cause Mortality
    DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 98/125 (78.4%) 46/55 (83.6%) 4/7 (57.1%) 50/62 (80.6%) 16/20 (80%) 21/24 (87.5%)
    Serious Adverse Events
    DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 58/125 (46.4%) 15/55 (27.3%) 1/7 (14.3%) 16/62 (25.8%) 6/20 (30%) 11/24 (45.8%)
    Blood and lymphatic system disorders
    Anaemia 4/125 (3.2%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 0/20 (0%) 0/24 (0%)
    Febrile neutropenia 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Disseminated intravascular coagulation 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Neutropenia 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Cardiac disorders
    Pericardial effusion 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Acute coronary syndrome 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Stress cardiomyopathy 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Congenital, familial and genetic disorders
    Pyloric stenosis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Eye disorders
    Cataract 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Glaucoma 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Gastrointestinal disorders
    Gastric haemorrhage 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 2/24 (8.3%)
    Abdominal distension 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 1/24 (4.2%)
    Abdominal pain 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 1/24 (4.2%)
    Ascites 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Diarrhoea 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Gastric stenosis 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Gastrointestinal obstruction 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Anal stenosis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Inguinal hernia 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Large intestine perforation 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Nausea 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Oesophageal stenosis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Pancreatitis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Stomatitis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Upper gastrointestinal haemorrhage 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Vomiting 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    General disorders
    Disease progression 3/125 (2.4%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 2/20 (10%) 0/24 (0%)
    Pyrexia 3/125 (2.4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 1/24 (4.2%)
    Fatigue 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 1/24 (4.2%)
    Asthenia 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Condition aggravated 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    General physical health deterioration 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Hepatobiliary disorders
    Jaundice cholestatic 3/125 (2.4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 1/24 (4.2%)
    Cholangitis 3/125 (2.4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 1/24 (4.2%)
    Hepatic function abnormal 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Bile duct stone 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Cholangitis acute 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Liver disorder 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Bile duct obstruction 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Liver injury 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Infections and infestations
    Pneumonia 3/125 (2.4%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Sepsis 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 1/24 (4.2%)
    Lung infection 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 1/24 (4.2%)
    Pneumonia bacterial 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Bacteraemia 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Biliary sepsis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Biliary tract infection 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Device-related infection 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Infectious pleural effusion 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Cholangitis infective 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Ulna fracture 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Investigations
    Blood creatinine increased 0/125 (0%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 0/20 (0%) 0/24 (0%)
    Neutrophil count decreased 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Platelet count decreased 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    White blood cell count decreased 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 13/125 (10.4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 2/20 (10%) 4/24 (16.7%)
    Dehydration 4/125 (3.2%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Hypophagia 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Musculoskeletal and connective tissue disorders
    Neck pain 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage 3/125 (2.4%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Neoplasm progression 2/125 (1.6%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Pericarditis malignant 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Tumour pain 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Cancer pain 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Nervous system disorders
    Cerebral infarction 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Dizziness 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Hemiplegia 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Presyncope 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Renal and urinary disorders
    Hydronephrosis 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 1/24 (4.2%)
    Acute kidney injury 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis 5/125 (4%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Interstitial lung disease 3/125 (2.4%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Pneumonia aspiration 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Vascular disorders
    Hypotension 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Embolism 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 1/24 (4.2%)
    Other (Not Including Serious) Adverse Events
    DS-8201a Physician's Choice Irinotecan Physician's Choice Paclitaxel Physician's Choice Overall Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a Exploratory: Naïve HER2 IHC 1+, DS-8201a
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 125/125 (100%) 54/55 (98.2%) 7/7 (100%) 61/62 (98.4%) 20/20 (100%) 24/24 (100%)
    Blood and lymphatic system disorders
    Anaemia 71/125 (56.8%) 17/55 (30.9%) 2/7 (28.6%) 19/62 (30.6%) 10/20 (50%) 11/24 (45.8%)
    Febrile neutropenia 6/125 (4.8%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 1/20 (5%) 0/24 (0%)
    Neutropenia 3/125 (2.4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Eye disorders
    Keratitis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Corneal erosion 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Gastrointestinal disorders
    Nausea 79/125 (63.2%) 27/55 (49.1%) 2/7 (28.6%) 29/62 (46.8%) 11/20 (55%) 19/24 (79.2%)
    Diarrhoea 41/125 (32.8%) 20/55 (36.4%) 0/7 (0%) 20/62 (32.3%) 6/20 (30%) 8/24 (33.3%)
    Constipation 31/125 (24.8%) 13/55 (23.6%) 2/7 (28.6%) 15/62 (24.2%) 5/20 (25%) 5/24 (20.8%)
    Vomiting 33/125 (26.4%) 5/55 (9.1%) 0/7 (0%) 5/62 (8.1%) 4/20 (20%) 7/24 (29.2%)
    Abdominal pain 14/125 (11.2%) 8/55 (14.5%) 0/7 (0%) 8/62 (12.9%) 2/20 (10%) 1/24 (4.2%)
    Stomatitis 14/125 (11.2%) 2/55 (3.6%) 1/7 (14.3%) 3/62 (4.8%) 2/20 (10%) 2/24 (8.3%)
    Ascites 8/125 (6.4%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 3/20 (15%) 3/24 (12.5%)
    Abdominal distension 4/125 (3.2%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 2/20 (10%) 2/24 (8.3%)
    Dyspepsia 4/125 (3.2%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 0/20 (0%) 2/24 (8.3%)
    Abdominal pain upper 5/125 (4%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Gastric haemorrhage 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 2/24 (8.3%)
    Oesophageal stenosis 2/125 (1.6%) 1/55 (1.8%) 1/7 (14.3%) 2/62 (3.2%) 0/20 (0%) 0/24 (0%)
    Anal haemorrhage 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Cheilitis 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Periodontal disease 2/125 (1.6%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    General disorders
    Malaise 44/125 (35.2%) 9/55 (16.4%) 1/7 (14.3%) 10/62 (16.1%) 4/20 (20%) 9/24 (37.5%)
    Fatigue 27/125 (21.6%) 15/55 (27.3%) 0/7 (0%) 15/62 (24.2%) 5/20 (25%) 6/24 (25%)
    Pyrexia 31/125 (24.8%) 8/55 (14.5%) 2/7 (28.6%) 10/62 (16.1%) 3/20 (15%) 6/24 (25%)
    Oedema peripheral 15/125 (12%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 4/20 (20%) 2/24 (8.3%)
    Disease progression 3/125 (2.4%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 2/20 (10%) 0/24 (0%)
    Asthenia 1/125 (0.8%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 0/20 (0%) 2/24 (8.3%)
    Influenza-like illness 0/125 (0%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Injection site extravasation 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Hepatobiliary disorders
    Hepatic function abnormal 10/125 (8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 1/24 (4.2%)
    Jaundice cholestatic 5/125 (4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 1/24 (4.2%)
    Infections and infestations
    Nasopharyngitis 11/125 (8.8%) 4/55 (7.3%) 1/7 (14.3%) 5/62 (8.1%) 1/20 (5%) 2/24 (8.3%)
    Pneumonia 7/125 (5.6%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 1/24 (4.2%)
    Upper respiratory tract infection 6/125 (4.8%) 1/55 (1.8%) 1/7 (14.3%) 2/62 (3.2%) 0/20 (0%) 1/24 (4.2%)
    Lung infection 6/125 (4.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 2/20 (10%) 1/24 (4.2%)
    Influenza 4/125 (3.2%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Pneumonia bacterial 3/125 (2.4%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Conjunctivitis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Folliculitis 1/125 (0.8%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Cellulitis 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Pneumonia staphylococcal 0/125 (0%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Sinusitis 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Subdural haemorrhage 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Ulna fracture 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Contusion 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Procedural pain 1/125 (0.8%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Investigations
    Neutrophil count decreased 79/125 (63.2%) 18/55 (32.7%) 3/7 (42.9%) 21/62 (33.9%) 8/20 (40%) 12/24 (50%)
    White blood cell count decreased 49/125 (39.2%) 18/55 (32.7%) 3/7 (42.9%) 21/62 (33.9%) 4/20 (20%) 7/24 (29.2%)
    Platelet count decreased 48/125 (38.4%) 4/55 (7.3%) 0/7 (0%) 4/62 (6.5%) 3/20 (15%) 7/24 (29.2%)
    Lymphocyte count decreased 30/125 (24%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 1/20 (5%) 3/24 (12.5%)
    Weight decreased 19/125 (15.2%) 5/55 (9.1%) 0/7 (0%) 5/62 (8.1%) 4/20 (20%) 7/24 (29.2%)
    Aspartate aminotransferase increased 12/125 (9.6%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 2/20 (10%) 1/24 (4.2%)
    Blood alkaline phosphatase increased 11/125 (8.8%) 1/55 (1.8%) 1/7 (14.3%) 2/62 (3.2%) 1/20 (5%) 4/24 (16.7%)
    Alanine aminotransferase increased 9/125 (7.2%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 1/20 (5%) 0/24 (0%)
    Blood bilirubin increased 10/125 (8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 1/24 (4.2%)
    Blood creatinine increased 1/125 (0.8%) 6/55 (10.9%) 0/7 (0%) 6/62 (9.7%) 2/20 (10%) 1/24 (4.2%)
    International normalised ratio increased 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Urine output decreased 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Lymphocyte count increased 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 76/125 (60.8%) 27/55 (49.1%) 1/7 (14.3%) 28/62 (45.2%) 13/20 (65%) 18/24 (75%)
    Hypoalbuminaemia 18/125 (14.4%) 7/55 (12.7%) 1/7 (14.3%) 8/62 (12.9%) 2/20 (10%) 5/24 (20.8%)
    Hypokalaemia 11/125 (8.8%) 4/55 (7.3%) 0/7 (0%) 4/62 (6.5%) 0/20 (0%) 4/24 (16.7%)
    Dehydration 8/125 (6.4%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 0/20 (0%) 0/24 (0%)
    Hyponatraemia 3/125 (2.4%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 1/20 (5%) 2/24 (8.3%)
    Hyperkalaemia 1/125 (0.8%) 3/55 (5.5%) 1/7 (14.3%) 4/62 (6.5%) 0/20 (0%) 1/24 (4.2%)
    Hypocalcaemia 1/125 (0.8%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 0/20 (0%) 1/24 (4.2%)
    Hypoglycaemia 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 2/24 (8.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 10/125 (8%) 2/55 (3.6%) 1/7 (14.3%) 3/62 (4.8%) 0/20 (0%) 1/24 (4.2%)
    Pain in extremity 3/125 (2.4%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 1/24 (4.2%)
    Myalgia 3/125 (2.4%) 1/55 (1.8%) 1/7 (14.3%) 2/62 (3.2%) 0/20 (0%) 0/24 (0%)
    Arthralgia 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 2/24 (8.3%)
    Musculoskeletal pain 1/125 (0.8%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Spinal osteoarthritis 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Joint range of motion decreased 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Spondylolisthesis 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 6/125 (4.8%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 0/20 (0%) 2/24 (8.3%)
    Tumour pain 2/125 (1.6%) 2/55 (3.6%) 1/7 (14.3%) 3/62 (4.8%) 2/20 (10%) 2/24 (8.3%)
    Neoplasm progression 2/125 (1.6%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Nervous system disorders
    Dysgeusia 9/125 (7.2%) 4/55 (7.3%) 0/7 (0%) 4/62 (6.5%) 4/20 (20%) 1/24 (4.2%)
    Dizziness 5/125 (4%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 1/20 (5%) 0/24 (0%)
    Headache 4/125 (3.2%) 4/55 (7.3%) 0/7 (0%) 4/62 (6.5%) 0/20 (0%) 0/24 (0%)
    Peripheral sensory neuropathy 4/125 (3.2%) 0/55 (0%) 2/7 (28.6%) 2/62 (3.2%) 2/20 (10%) 0/24 (0%)
    Cholinergic syndrome 0/125 (0%) 3/55 (5.5%) 0/7 (0%) 3/62 (4.8%) 0/20 (0%) 0/24 (0%)
    Cerebral infarction 0/125 (0%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Neuropathy peripheral 0/125 (0%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Brain oedema 0/125 (0%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Psychiatric disorders
    Insomnia 11/125 (8.8%) 4/55 (7.3%) 1/7 (14.3%) 5/62 (8.1%) 2/20 (10%) 1/24 (4.2%)
    Delirium 4/125 (3.2%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Renal and urinary disorders
    Hydronephrosis 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 1/24 (4.2%)
    Acute kidney injury 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Hiccups 6/125 (4.8%) 6/55 (10.9%) 0/7 (0%) 6/62 (9.7%) 1/20 (5%) 1/24 (4.2%)
    Pneumonitis 11/125 (8.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 0/24 (0%)
    Oropharyngeal pain 3/125 (2.4%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 2/20 (10%) 0/24 (0%)
    Pleural effusion 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 0/20 (0%) 2/24 (8.3%)
    Dysphonia 1/125 (0.8%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Dry throat 0/125 (0%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Interstitial lung disease 8/125 (6.4%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Skin and subcutaneous tissue disorders
    Alopecia 28/125 (22.4%) 8/55 (14.5%) 1/7 (14.3%) 9/62 (14.5%) 3/20 (15%) 1/24 (4.2%)
    Pruritus 10/125 (8%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 2/20 (10%) 0/24 (0%)
    Rash 6/125 (4.8%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 1/20 (5%) 0/24 (0%)
    Dry skin 9/125 (7.2%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 1/24 (4.2%)
    Rash maculo-papular 1/125 (0.8%) 1/55 (1.8%) 1/7 (14.3%) 2/62 (3.2%) 1/20 (5%) 0/24 (0%)
    Dermatitis acneiform 2/125 (1.6%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Nail disorder 0/125 (0%) 0/55 (0%) 1/7 (14.3%) 1/62 (1.6%) 0/20 (0%) 0/24 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Surgical and medical procedures
    Tooth extraction 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Vascular disorders
    Embolism 1/125 (0.8%) 1/55 (1.8%) 0/7 (0%) 1/62 (1.6%) 0/20 (0%) 3/24 (12.5%)
    Hypertension 0/125 (0%) 2/55 (3.6%) 0/7 (0%) 2/62 (3.2%) 1/20 (5%) 0/24 (0%)
    Flushing 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)
    Haemorrhage 0/125 (0%) 0/55 (0%) 0/7 (0%) 0/62 (0%) 1/20 (5%) 0/24 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Contact for Clinical Trial Information
    Organization Daiichi Sankyo
    Phone 908-992-6400
    Email CTRinfo@dsi.com
    Responsible Party:
    Daiichi Sankyo Co., Ltd.
    ClinicalTrials.gov Identifier:
    NCT03329690
    Other Study ID Numbers:
    • DS8201-A-J202
    • 173727
    • DESTINY-G01
    First Posted:
    Nov 6, 2017
    Last Update Posted:
    Mar 18, 2022
    Last Verified:
    Mar 1, 2022