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

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ClinicalTrials.gov Identifier: NCT03329690
Recruitment Status : Completed
First Posted : November 6, 2017
Results First Posted : November 27, 2020
Last Update Posted : February 23, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasm, Gastrointestinal
Interventions Drug: DS-8201a
Drug: Physician's Choice
Enrollment 233
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.
Pre-assignment Details 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
Hide 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 [1] 28 2 1 0 2
Not Completed 98 53 6 21 22
Reason Not Completed
Progressive disease per RECIST             67             42             5             16             19
Clinical progression             6             4             1             1             0
Adverse Event             19             4             0             1             2
Death             2             0             0             1             0
Withdrawal by Subject             2             3             0             1             0
Physician Decision             1             0             0             0             1
Did not receive treatment             1             0             0             1             0
[1]
Ongoing as of database lock 8 Nov 2019
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
Hide 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 Number of Baseline Participants 125 55 7 20 24 231
Hide Baseline Analysis Population Description
Baseline and demographic characteristics were assessed in the Full Analysis Set.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 55 participants 7 participants 20 participants 24 participants 231 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
55
  44.0%
24
  43.6%
3
  42.9%
11
  55.0%
17
  70.8%
110
  47.6%
>=65 years
70
  56.0%
31
  56.4%
4
  57.1%
9
  45.0%
7
  29.2%
121
  52.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 125 participants 55 participants 7 participants 20 participants 24 participants 231 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 55 participants 7 participants 20 participants 24 participants 231 participants
Female
30
  24.0%
13
  23.6%
2
  28.6%
4
  20.0%
7
  29.2%
56
  24.2%
Male
95
  76.0%
42
  76.4%
5
  71.4%
16
  80.0%
17
  70.8%
175
  75.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 55 participants 7 participants 20 participants 24 participants 231 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
125
 100.0%
55
 100.0%
7
 100.0%
20
 100.0%
24
 100.0%
231
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
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%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
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%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 55 participants 7 participants 20 participants 24 participants 231 participants
South Korea 26 11 1 4 5 47
Japan 99 44 6 16 19 184
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 126 55 7 62
Measure Type: Count of Participants
Unit of Measure: Participants
Unconfirmed ORR
61
  48.4%
7
  12.7%
1
  14.3%
8
  12.9%
Confirmed ORR
51
  40.5%
6
  10.9%
1
  14.3%
7
  11.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DS-8201a, Physician's Choice Overall
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 126 55 7 62
Measure Type: Count of Participants
Unit of Measure: Participants
Unconfirmed Complete response (CR)
11
   8.7%
0
   0.0%
0
   0.0%
0
   0.0%
Unconfirmed Partial response (PR)
50
  39.7%
7
  12.7%
1
  14.3%
8
  12.9%
Unconfirmed Stable disease (SD)
46
  36.5%
27
  49.1%
3
  42.9%
30
  48.4%
Unconfirmed Progressive disease (PD)
15
  11.9%
18
  32.7%
0
   0.0%
18
  29.0%
Unconfirmed Not evaluable (NE)
4
   3.2%
3
   5.5%
3
  42.9%
6
   9.7%
Confirmed Complete response (CR)
10
   7.9%
0
   0.0%
0
   0.0%
0
   0.0%
Confirmed Partial response (PR)
41
  32.5%
6
  10.9%
1
  14.3%
7
  11.3%
Confirmed Stable disease (SD)
55
  43.7%
28
  50.9%
3
  42.9%
31
  50.0%
Confirmed Progressive disease (PD)
15
  11.9%
18
  32.7%
0
   0.0%
18
  29.0%
Confirmed Not evaluable (NE)
5
   4.0%
3
   5.5%
3
  42.9%
6
   9.7%
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 126 55 7 62 21 22
Median (Full Range)
Unit of Measure: months
Duration of survival follow up
8.0
(0.4 to 23.1)
7.1
(0.3 to 20.3)
5.5
(2.0 to 14.3)
7.0
(0.3 to 20.3)
7.3
(0.2 to 19.6)
8.4
(1.8 to 14.8)
Overall survival
12.5
(0.4 to 23.1)
8.4
(0.3 to 20.3)
14.3
(2.0 to 14.3)
8.4
(0.3 to 20.3)
7.8
(0.2 to 19.6)
8.5
(1.8 to 14.8)
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 126 55 7 62 21 22
Median (95% Confidence Interval)
Unit of Measure: months
5.6
(4.3 to 6.9)
2.8
(2.0 to 4.3)
4.9 [1] 
(2.0 to NA)
3.5
(2.0 to 4.3)
4.4
(2.7 to 7.1)
2.8
(1.5 to 4.3)
[1]
Missing upper limit was not calculable due to right censored data; last timepoint censored and estimate is infinity
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 61 7 1 8 7 4
Median (Full Range)
Unit of Measure: months
Unconfirmed Duration of response (DOR) Number Analyzed 61 participants 7 participants 1 participants 8 participants 7 participants 4 participants
8.4
(0 to 21)
4.1
(0 to 4.9)
3.9
(3.9 to 3.9)
3.9
(0 to 4.9)
6.8
(1.4 to 9.7)
7.1
(1.4 to 12.5)
Confirmed Duration of response (DOR) Number Analyzed 51 participants 6 participants 1 participants 7 participants 5 participants 2 participants
11.3
(1.4 to 21.0)
4.1
(1.4 to 4.9)
3.9
(3.9 to 3.9)
3.9
(1.4 to 4.9)
7.6
(2.4 to 9.7)
12.5
(8.1 to 12.5)
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 126 55 7 62 21 22
Measure Type: Count of Participants
Unit of Measure: Participants
107
  84.9%
34
  61.8%
4
  57.1%
38
  61.3%
17
  81.0%
15
  68.2%
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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 21 22
Measure Type: Count of Participants
Unit of Measure: Participants
Confirmed Objective response rate (ORR)
7
  33.3%
4
  18.2%
Confirmed Complete response (CR)
0
   0.0%
0
   0.0%
Confirmed Partial response (PR)
7
  33.3%
4
  18.2%
Confirmed Stable disease (SD)
10
  47.6%
11
  50.0%
Confirmed Progressive disease (PD)
3
  14.3%
6
  27.3%
Inevaluable
1
   4.8%
1
   4.5%
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)
Hide 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 25 months postdose
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 125 55 7 62 20 22
Median (95% Confidence Interval)
Unit of Measure: months
4.2
(3.9 to 5.1)
2.6
(1.6 to 2.8)
2.9
(1.1 to 6.8)
2.6
(1.6 to 2.8)
3.7
(1.7 to 5.5)
2.2
(1.4 to 3.0)
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)
Hide 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 25 months postdose
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Hide 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
Hide 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.
Overall Number of Participants Analyzed 119 51 5 56 19 21
Measure Type: Count of Participants
Unit of Measure: Participants
Unconfirmed Objective response rate (ORR)
60
  50.4%
7
  13.7%
1
  20.0%
8
  14.3%
10
  52.6%
5
  23.8%
Unconfirmed Complete response (CR)
4
   3.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unconfirmed Partial response (PR)
56
  47.1%
7
  13.7%
1
  20.0%
8
  14.3%
10
  52.6%
5
  23.8%
Unconfirmed Stable disease (SD)
42
  35.3%
27
  52.9%
1
  20.0%
28
  50.0%
7
  36.8%
8
  38.1%
Unconfirmed Progressive disease (PD)
15
  12.6%
15
  29.4%
2
  40.0%
17
  30.4%
2
  10.5%
8
  38.1%
Unconfirmed Not evaluable (NE)
2
   1.7%
2
   3.9%
1
  20.0%
3
   5.4%
0
   0.0%
0
   0.0%
Confirmed Objective response rate (ORR)
49
  41.2%
5
   9.8%
1
  20.0%
6
  10.7%
8
  42.1%
3
  14.3%
Confirmed Complete response (CR)
3
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Confirmed Partial response (PR)
46
  38.7%
5
   9.8%
1
  20.0%
6
  10.7%
8
  42.1%
3
  14.3%
Confirmed Stable disease (SD)
53
  44.5%
28
  54.9%
1
  20.0%
29
  51.8%
9
  47.4%
10
  47.6%
Confirmed Progressive disease (PD)
15
  12.6%
16
  31.4%
2
  40.0%
18
  32.1%
2
  10.5%
8
  38.1%
Confirmed Not evaluable (NE)
2
   1.7%
2
   3.9%
1
  20.0%
3
   5.4%
0
   0.0%
0
   0.0%
10.Secondary Outcome
Title Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a, Total Anti-HER2 Antibody, and MAAA-1181 Following Treatment With DS-8201a
Hide 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, 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 125 20 24
Mean (Standard Deviation)
Unit of Measure: ug/mL
Cmax: DS-8201a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
127  (28.4) 119  (29.1) 127  (24.5)
Cmax: DS-8201a, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
137  (31.1) 128  (25.6) 123  (23.2)
Cmax: Total Anti-HER2 antibody, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
116  (30.6) 105  (26.1) 110  (19.6)
Cmax: Total Anti-HER2 antibody, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
121  (28.4) 115  (24.2) 112  (21.9)
Cmax: MAAA-1181a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
12.1  (4.79) 13.3  (8.52) 13.3  (7.37)
Cmax: MAAA-1181a, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
9.08  (3.81) 7.62  (1.86) 9.83  (3.75)
Ctrough: DS-8201a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
5.56  (3.08) 4.52  (2.42) 9.51  (23.4)
Ctrough: DS-8201a, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
13.4  (17.3) 8.84  (3.09) 13.2  (18.6)
Ctrough: Total Anti-HER2 antibody, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
8.56  (8.60) 5.33  (2.97) 10.0  (20.5)
Ctrough: Total Anti-HER2 antibody, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
15.6  (13.6) 12.2  (5.76) 14.6  (17.6)
Ctrough: MAAA-1181a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
0.316  (0.294) 0.290  (0.237) 0.772  (2.28)
Ctrough: MAAA-1181a, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
0.714  (2.19) 0.378  (0.138) 1.10  (1.95)
11.Secondary Outcome
Title Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Hide 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, 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 125 20 24
Mean (Standard Deviation)
Unit of Measure: ug*d/mL
AUClast: DS-8201a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
611  (150) 572  (143) 545  (160)
AUClast: DS-8201a, Cycle 3 Number Analyzed 0 participants 0 participants 0 participants
AUClast: Total Anti-HER2 antibody, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
667  (241) 570  (126) 547  (167)
AUClast: Total Anti-HER2 antibody, Cycle 3 Number Analyzed 0 participants 0 participants 0 participants
AUClast: MAAA-1181a, Cycle 1 Number Analyzed 125 participants 20 participants 0 participants
46.7  (16.3) 53.4  (42.7)
AUClast: MAAA-1181a, Cycle 3 Number Analyzed 0 participants 0 participants 0 participants
AUC21d: DS-8201a, Cycle 1 Number Analyzed 124 participants 20 participants 23 participants
612  (150) 572  (143) 569  (114)
AUC21d: DS-8201a, Cycle 3 Number Analyzed 66 participants 10 participants 10 participants
867  (213) 746  (197) 724  (71.9)
AUC21d: Total Anti-HER2 antibody, Cycle 1 Number Analyzed 121 participants 20 participants 22 participants
651  (210) 570  (126) 582  (104)
AUC21d: Total Anti-HER2 antibody, Cycle 3 Number Analyzed 66 participants 11 participants 9 participants
888  (244) 775  (210) 737  (110)
AUC21d: MAAA-1181a, Cycle 1 Number Analyzed 107 participants 19 participants 22 participants
46.4  (16.1) 44.9  (20.1) 44.5  (22.5)
AUC21d: MAAA-1181a, Cycle 3 Number Analyzed 54 participants 10 participants 8 participants
42.0  (15.1) 39.4  (8.36) 44.6  (17.8)
12.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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 125 20 24
Median (Full Range)
Unit of Measure: hours
DS-8201a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
3.93
(0 to 7.15)
3.90
(1.58 to 7.12)
3.89
(1.53 to 7.08)
DS-8201a, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
4.00
(0.58 to 7.25)
4.00
(0.58 to 6.82)
4.00
(0.68 to 7.02)
Total Anti-HER2 antibody, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
3.83
(0 to 7.15)
3.83
(1.58 to 7.08)
3.87
(1.53 to 7.08)
Total Anti-HER2 antibody, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
3.98
(0.53 to 7.17)
4.00
(0.57 to 6.83)
3.75
(0.53 to 7.03)
MAAA-1181a, Cycle 1 Number Analyzed 125 participants 20 participants 24 participants
6.85
(3.75 to 7.25)
6.83
(3.83 to 141.73)
6.81
(3.83 to 7.08)
MAAA-1181a, Cycle 3 Number Analyzed 69 participants 11 participants 11 participants
6.80
(3.78 to 7.25)
6.82
(3.88 to 7.10)
6.77
(3.98 to 7.07)
13.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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 124 20 23
Mean (Standard Deviation)
Unit of Measure: days
DS-8201a, Cycle 1 Number Analyzed 124 participants 20 participants 23 participants
5.77  (1.37) 5.54  (1.08) 5.52  (1.17)
DS-8201a, Cycle 3 Number Analyzed 66 participants 10 participants 10 participants
7.46  (1.82) 6.40  (1.00) 6.35  (1.73)
Total Anti-HER2 antibody, Cycle 1 Number Analyzed 121 participants 20 participants 22 participants
6.20  (2.22) 5.54  (1.01) 5.65  (1.51)
Total Anti-HER2 antibody, Cycle 3 Number Analyzed 66 participants 11 participants 9 participants
8.00  (2.04) 7.90  (2.10) 6.17  (1.15)
MAAA-1181a, Cycle 1 Number Analyzed 98 participants 17 participants 22 participants
5.50  (1.11) 5.21  (0.939) 5.61  (1.19)
MAAA-1181a, Cycle 3 Number Analyzed 50 participants 10 participants 7 participants
7.01  (1.65) 6.18  (1.02) 5.80  (1.10)
14.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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 125 55 7 62 20 24
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
125
 100.0%
54
  98.2%
7
 100.0%
61
  98.4%
20
 100.0%
24
 100.0%
Drug-related TEAEs
122
  97.6%
51
  92.7%
5
  71.4%
56
  90.3%
19
  95.0%
24
 100.0%
Serious TEAEs
55
  44.0%
14
  25.5%
1
  14.3%
15
  24.2%
6
  30.0%
11
  45.8%
Drug-related serious TEAEs
27
  21.6%
5
   9.1%
0
   0.0%
5
   8.1%
1
   5.0%
6
  25.0%
TEAEs associated with drug withdrawn
19
  15.2%
4
   7.3%
0
   0.0%
4
   6.5%
2
  10.0%
1
   4.2%
Drug-related TEAEs associated with drug withdrawn
12
   9.6%
3
   5.5%
0
   0.0%
3
   4.8%
1
   5.0%
0
   0.0%
TEAEs associated with dose reduced
40
  32.0%
21
  38.2%
0
   0.0%
21
  33.9%
6
  30.0%
8
  33.3%
Drug-related TEAEs associated with dose reduced
38
  30.4%
21
  38.2%
0
   0.0%
21
  33.9%
6
  30.0%
7
  29.2%
TEAEs associated with drug interrupted
78
  62.4%
20
  36.4%
3
  42.9%
23
  37.1%
8
  40.0%
10
  41.7%
Drug-related TEAE associated with drug interrupted
64
  51.2%
17
  30.9%
2
  28.6%
19
  30.6%
7
  35.0%
10
  41.7%
TEAEs associated with death
8
   6.4%
1
   1.8%
1
  14.3%
2
   3.2%
2
  10.0%
0
   0.0%
15.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)
Hide 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 25 months postdose
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 125 55 7 62 20 24
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
125
 100.0%
54
  98.2%
7
 100.0%
61
  98.4%
20
 100.0%
24
 100.0%
Nausea
79
  63.2%
27
  49.1%
2
  28.6%
29
  46.8%
11
  55.0%
19
  79.2%
Decreased appetite
75
  60.0%
27
  49.1%
1
  14.3%
28
  45.2%
13
  65.0%
18
  75.0%
Neutrophil count decreased
77
  61.6%
18
  32.7%
3
  42.9%
21
  33.9%
8
  40.0%
12
  50.0%
Anaemia
71
  56.8%
17
  30.9%
2
  28.6%
19
  30.6%
10
  50.0%
10
  41.7%
White blood cell count decreased
47
  37.6%
18
  32.7%
3
  42.9%
21
  33.9%
4
  20.0%
7
  29.2%
Platelet count decreased
47
  37.6%
4
   7.3%
0
   0.0%
4
   6.5%
3
  15.0%
7
  29.2%
Malaise
43
  34.4%
9
  16.4%
1
  14.3%
10
  16.1%
4
  20.0%
9
  37.5%
Diarrhoea
40
  32.0%
20
  36.4%
0
   0.0%
20
  32.3%
6
  30.0%
8
  33.3%
Vomiting
33
  26.4%
5
   9.1%
0
   0.0%
5
   8.1%
4
  20.0%
7
  29.2%
Constipation
30
  24.0%
13
  23.6%
1
  14.3%
14
  22.6%
5
  25.0%
5
  20.8%
Pyrexia
30
  24.0%
8
  14.5%
2
  28.6%
10
  16.1%
3
  15.0%
6
  25.0%
Fatigue
27
  21.6%
15
  27.3%
0
   0.0%
15
  24.2%
5
  25.0%
6
  25.0%
Alopecia
28
  22.4%
8
  14.5%
1
  14.3%
9
  14.5%
3
  15.0%
1
   4.2%
Lymphocyte count decreased
27
  21.6%
2
   3.6%
0
   0.0%
2
   3.2%
1
   5.0%
3
  12.5%
Weight decreased
17
  13.6%
5
   9.1%
0
   0.0%
5
   8.1%
4
  20.0%
7
  29.2%
Hypoalbuminaemia
18
  14.4%
7
  12.7%
1
  14.3%
8
  12.9%
2
  10.0%
5
  20.8%
Oedema peripheral
13
  10.4%
0
   0.0%
0
   0.0%
0
   0.0%
4
  20.0%
1
   4.2%
Dysgeusia
9
   7.2%
4
   7.3%
0
   0.0%
4
   6.5%
4
  20.0%
1
   4.2%
Peripheral sensory neuropathy
4
   3.2%
0
   0.0%
2
  28.6%
2
   3.2%
2
  10.0%
0
   0.0%
Time Frame Treatment-emergent adverse event (TEAE) data were collected from baseline up to 47 days after last dose, up to 25 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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   62/125 (49.60%)   35/55 (63.64%)   4/7 (57.14%)   39/62 (62.90%)   12/20 (60.00%)   19/24 (79.17%) 
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   55/125 (44.00%)   14/55 (25.45%)   1/7 (14.29%)   15/62 (24.19%)   6/20 (30.00%)   11/24 (45.83%) 
Blood and lymphatic system disorders             
Anaemia  1  4/125 (3.20%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  0/20 (0.00%)  0/24 (0.00%) 
Febrile neutropenia  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Disseminated intravascular coagulation  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Neutropenia  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Cardiac disorders             
Pericardial effusion  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Acute coronary syndrome  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Stress cardiomyopathy  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Congenital, familial and genetic disorders             
Pyloric stenosis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Gastrointestinal disorders             
Gastric haemorrhage  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  2/24 (8.33%) 
Abdominal distension  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  1/24 (4.17%) 
Abdominal pain  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  1/24 (4.17%) 
Ascites  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Diarrhoea  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Gastric stenosis  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Gastrointestinal obstruction  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Anal stenosis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Inguinal hernia  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Large intestine perforation  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Nausea  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Oesophageal stenosis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Pancreatitis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Stomatitis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Vomiting  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
General disorders             
Disease progression  1  3/125 (2.40%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  2/20 (10.00%)  0/24 (0.00%) 
Pyrexia  1  3/125 (2.40%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  1/24 (4.17%) 
Fatigue  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  1/24 (4.17%) 
Asthenia  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Condition aggravated  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
General physical health deterioration  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Hepatobiliary disorders             
Jaundice cholestatic  1  3/125 (2.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Cholangitis  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  1/24 (4.17%) 
Hepatic function abnormal  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Bile duct stone  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Cholangitis acute  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Liver disorder  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Bile duct obstruction  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Liver injury  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Infections and infestations             
Pneumonia  1  3/125 (2.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Sepsis  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  1/24 (4.17%) 
Lung infection  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  1/24 (4.17%) 
Pneumonia bacterial  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Bacteraemia  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Biliary sepsis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Biliary tract infection  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Device-related infection  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Infectious pleural effusion  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Cholangitis infective  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications             
Ulna fracture  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Investigations             
Blood creatinine increased  1  0/125 (0.00%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  0/20 (0.00%)  0/24 (0.00%) 
Neutrophil count decreased  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Platelet count decreased  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
White blood cell count decreased  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite  1  13/125 (10.40%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  2/20 (10.00%)  4/24 (16.67%) 
Dehydration  1  4/125 (3.20%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Hypophagia  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Musculoskeletal and connective tissue disorders             
Neck pain  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Tumour haemorrhage  1  3/125 (2.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Neoplasm progression  1  2/125 (1.60%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Pericarditis malignant  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Tumour pain  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Cancer pain  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Nervous system disorders             
Cerebral infarction  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Dizziness  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Hemiplegia  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Presyncope  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Renal and urinary disorders             
Hydronephrosis  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  1/24 (4.17%) 
Acute kidney injury  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Pneumonitis  1  3/125 (2.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Interstitial lung disease  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Pneumonia aspiration  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Vascular disorders             
Hypotension  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Embolism  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  1/24 (4.17%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   125/125 (100.00%)   54/55 (98.18%)   7/7 (100.00%)   61/62 (98.39%)   20/20 (100.00%)   24/24 (100.00%) 
Blood and lymphatic system disorders             
Anaemia  1  71/125 (56.80%)  17/55 (30.91%)  2/7 (28.57%)  19/62 (30.65%)  10/20 (50.00%)  10/24 (41.67%) 
Febrile neutropenia  1  6/125 (4.80%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  1/20 (5.00%)  0/24 (0.00%) 
Neutropenia  1  3/125 (2.40%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Eye disorders             
Keratitis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Corneal erosion  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Gastrointestinal disorders             
Nausea  1  79/125 (63.20%)  27/55 (49.09%)  2/7 (28.57%)  29/62 (46.77%)  11/20 (55.00%)  19/24 (79.17%) 
Diarrhoea  1  40/125 (32.00%)  20/55 (36.36%)  0/7 (0.00%)  20/62 (32.26%)  6/20 (30.00%)  8/24 (33.33%) 
Constipation  1  30/125 (24.00%)  13/55 (23.64%)  1/7 (14.29%)  14/62 (22.58%)  5/20 (25.00%)  5/24 (20.83%) 
Vomiting  1  33/125 (26.40%)  5/55 (9.09%)  0/7 (0.00%)  5/62 (8.06%)  4/20 (20.00%)  7/24 (29.17%) 
Abdominal pain  1  12/125 (9.60%)  8/55 (14.55%)  0/7 (0.00%)  8/62 (12.90%)  2/20 (10.00%)  1/24 (4.17%) 
Stomatitis  1  14/125 (11.20%)  2/55 (3.64%)  1/7 (14.29%)  3/62 (4.84%)  2/20 (10.00%)  2/24 (8.33%) 
Ascites  1  7/125 (5.60%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  3/20 (15.00%)  3/24 (12.50%) 
Abdominal distension  1  4/125 (3.20%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  2/20 (10.00%)  2/24 (8.33%) 
Dyspepsia  1  4/125 (3.20%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  0/20 (0.00%)  2/24 (8.33%) 
Abdominal pain upper  1  5/125 (4.00%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Gastric haemorrhage  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  2/24 (8.33%) 
Oesophageal stenosis  1  2/125 (1.60%)  1/55 (1.82%)  1/7 (14.29%)  2/62 (3.23%)  0/20 (0.00%)  0/24 (0.00%) 
Anal haemorrhage  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Cheilitis  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
General disorders             
Malaise  1  43/125 (34.40%)  9/55 (16.36%)  1/7 (14.29%)  10/62 (16.13%)  4/20 (20.00%)  9/24 (37.50%) 
Fatigue  1  27/125 (21.60%)  15/55 (27.27%)  0/7 (0.00%)  15/62 (24.19%)  5/20 (25.00%)  6/24 (25.00%) 
Pyrexia  1  30/125 (24.00%)  8/55 (14.55%)  2/7 (28.57%)  10/62 (16.13%)  3/20 (15.00%)  6/24 (25.00%) 
Oedema peripheral  1  13/125 (10.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  4/20 (20.00%)  1/24 (4.17%) 
Disease progression  1  3/125 (2.40%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  2/20 (10.00%)  0/24 (0.00%) 
Asthenia  1  1/125 (0.80%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  0/20 (0.00%)  2/24 (8.33%) 
Influenza-like illness  1  0/125 (0.00%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Injection site extravasation  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Hepatobiliary disorders             
Hepatic function abnormal  1  10/125 (8.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  1/24 (4.17%) 
Jaundice cholestatic  1  5/125 (4.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Infections and infestations             
Nasopharyngitis  1  10/125 (8.00%)  4/55 (7.27%)  1/7 (14.29%)  5/62 (8.06%)  0/20 (0.00%)  2/24 (8.33%) 
Pneumonia  1  7/125 (5.60%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  1/24 (4.17%) 
Upper respiratory tract infection  1  6/125 (4.80%)  1/55 (1.82%)  1/7 (14.29%)  2/62 (3.23%)  0/20 (0.00%)  1/24 (4.17%) 
Lung infection  1  5/125 (4.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  2/20 (10.00%)  1/24 (4.17%) 
Influenza  1  3/125 (2.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Pneumonia bacterial  1  3/125 (2.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Conjunctivitis  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Folliculitis  1  1/125 (0.80%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Cellulitis  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Pneumonia staphylococcal  1  0/125 (0.00%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Sinusitis  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications             
Subdural haemorrhage  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Ulna fracture  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Contusion  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Investigations             
Neutrophil count decreased  1  77/125 (61.60%)  18/55 (32.73%)  3/7 (42.86%)  21/62 (33.87%)  8/20 (40.00%)  12/24 (50.00%) 
White blood cell count decreased  1  47/125 (37.60%)  18/55 (32.73%)  3/7 (42.86%)  21/62 (33.87%)  4/20 (20.00%)  7/24 (29.17%) 
Platelet count decreased  1  47/125 (37.60%)  4/55 (7.27%)  0/7 (0.00%)  4/62 (6.45%)  3/20 (15.00%)  7/24 (29.17%) 
Lymphocyte count decreased  1  27/125 (21.60%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  1/20 (5.00%)  3/24 (12.50%) 
Weight decreased  1  17/125 (13.60%)  5/55 (9.09%)  0/7 (0.00%)  5/62 (8.06%)  4/20 (20.00%)  7/24 (29.17%) 
Aspartate aminotransferase increased  1  12/125 (9.60%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  2/20 (10.00%)  1/24 (4.17%) 
Blood alkaline phosphatase increased  1  10/125 (8.00%)  1/55 (1.82%)  1/7 (14.29%)  2/62 (3.23%)  1/20 (5.00%)  4/24 (16.67%) 
Alanine aminotransferase increased  1  9/125 (7.20%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  1/20 (5.00%)  0/24 (0.00%) 
Blood bilirubin increased  1  10/125 (8.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  1/24 (4.17%) 
Blood creatinine increased  1  1/125 (0.80%)  6/55 (10.91%)  0/7 (0.00%)  6/62 (9.68%)  1/20 (5.00%)  1/24 (4.17%) 
International normalised ratio increased  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Urine output decreased  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite  1  75/125 (60.00%)  27/55 (49.09%)  1/7 (14.29%)  28/62 (45.16%)  13/20 (65.00%)  18/24 (75.00%) 
Hypoalbuminaemia  1  18/125 (14.40%)  7/55 (12.73%)  1/7 (14.29%)  8/62 (12.90%)  2/20 (10.00%)  5/24 (20.83%) 
Hypokalaemia  1  8/125 (6.40%)  4/55 (7.27%)  0/7 (0.00%)  4/62 (6.45%)  0/20 (0.00%)  3/24 (12.50%) 
Dehydration  1  8/125 (6.40%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  0/20 (0.00%)  0/24 (0.00%) 
Hyponatraemia  1  3/125 (2.40%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  1/20 (5.00%)  2/24 (8.33%) 
Hyperkalaemia  1  1/125 (0.80%)  3/55 (5.45%)  1/7 (14.29%)  4/62 (6.45%)  0/20 (0.00%)  1/24 (4.17%) 
Hypocalcaemia  1  1/125 (0.80%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  0/20 (0.00%)  1/24 (4.17%) 
Hypoglycaemia  1  2/125 (1.60%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  2/24 (8.33%) 
Musculoskeletal and connective tissue disorders             
Back pain  1  9/125 (7.20%)  2/55 (3.64%)  1/7 (14.29%)  3/62 (4.84%)  0/20 (0.00%)  1/24 (4.17%) 
Pain in extremity  1  3/125 (2.40%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  1/24 (4.17%) 
Myalgia  1  3/125 (2.40%)  1/55 (1.82%)  1/7 (14.29%)  2/62 (3.23%)  0/20 (0.00%)  0/24 (0.00%) 
Arthralgia  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  2/24 (8.33%) 
Musculoskeletal pain  1  1/125 (0.80%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Spinal osteoarthritis  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Joint range of motion decreased  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Spondylolisthesis  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Cancer pain  1  5/125 (4.00%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  0/20 (0.00%)  2/24 (8.33%) 
Tumour pain  1  2/125 (1.60%)  2/55 (3.64%)  1/7 (14.29%)  3/62 (4.84%)  2/20 (10.00%)  2/24 (8.33%) 
Neoplasm progression  1  2/125 (1.60%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Nervous system disorders             
Dysgeusia  1  9/125 (7.20%)  4/55 (7.27%)  0/7 (0.00%)  4/62 (6.45%)  4/20 (20.00%)  1/24 (4.17%) 
Dizziness  1  5/125 (4.00%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  1/20 (5.00%)  0/24 (0.00%) 
Headache  1  4/125 (3.20%)  4/55 (7.27%)  0/7 (0.00%)  4/62 (6.45%)  0/20 (0.00%)  0/24 (0.00%) 
Peripheral sensory neuropathy  1  4/125 (3.20%)  0/55 (0.00%)  2/7 (28.57%)  2/62 (3.23%)  2/20 (10.00%)  0/24 (0.00%) 
Cholinergic syndrome  1  0/125 (0.00%)  3/55 (5.45%)  0/7 (0.00%)  3/62 (4.84%)  0/20 (0.00%)  0/24 (0.00%) 
Cerebral infarction  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Neuropathy peripheral  1  0/125 (0.00%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Psychiatric disorders             
Insomnia  1  11/125 (8.80%)  4/55 (7.27%)  1/7 (14.29%)  5/62 (8.06%)  2/20 (10.00%)  1/24 (4.17%) 
Delirium  1  4/125 (3.20%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Renal and urinary disorders             
Hydronephrosis  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  1/24 (4.17%) 
Acute kidney injury  1  0/125 (0.00%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Hiccups  1  6/125 (4.80%)  6/55 (10.91%)  0/7 (0.00%)  6/62 (9.68%)  1/20 (5.00%)  1/24 (4.17%) 
Pneumonitis  1  8/125 (6.40%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  0/24 (0.00%) 
Oropharyngeal pain  1  3/125 (2.40%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  2/20 (10.00%)  0/24 (0.00%) 
Pleural effusion  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  0/20 (0.00%)  2/24 (8.33%) 
Dysphonia  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Dry throat  1  0/125 (0.00%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Skin and subcutaneous tissue disorders             
Alopecia  1  28/125 (22.40%)  8/55 (14.55%)  1/7 (14.29%)  9/62 (14.52%)  3/20 (15.00%)  1/24 (4.17%) 
Pruritus  1  8/125 (6.40%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  2/20 (10.00%)  0/24 (0.00%) 
Rash  1  6/125 (4.80%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  1/20 (5.00%)  0/24 (0.00%) 
Dry skin  1  5/125 (4.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  1/24 (4.17%) 
Rash maculo-papular  1  1/125 (0.80%)  1/55 (1.82%)  1/7 (14.29%)  2/62 (3.23%)  1/20 (5.00%)  0/24 (0.00%) 
Dermatitis acneiform  1  1/125 (0.80%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Nail disorder  1  0/125 (0.00%)  0/55 (0.00%)  1/7 (14.29%)  1/62 (1.61%)  0/20 (0.00%)  0/24 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Surgical and medical procedures             
Tooth extraction  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Vascular disorders             
Embolism  1  1/125 (0.80%)  1/55 (1.82%)  0/7 (0.00%)  1/62 (1.61%)  0/20 (0.00%)  3/24 (12.50%) 
Hypertension  1  0/125 (0.00%)  2/55 (3.64%)  0/7 (0.00%)  2/62 (3.23%)  1/20 (5.00%)  0/24 (0.00%) 
Flushing  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
Haemorrhage  1  0/125 (0.00%)  0/55 (0.00%)  0/7 (0.00%)  0/62 (0.00%)  1/20 (5.00%)  0/24 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Contact for Clinical Trial Information
Organization: Daiichi Sankyo
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
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Responsible Party: Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
ClinicalTrials.gov Identifier: NCT03329690    
Other Study ID Numbers: DS8201-A-J202
173727 ( Registry Identifier: JAPIC CTI )
DESTINY-G01 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
First Submitted: October 30, 2017
First Posted: November 6, 2017
Results First Submitted: November 3, 2020
Results First Posted: November 27, 2020
Last Update Posted: February 23, 2021