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

• ClinicalTrials.gov Identifier: NCT03329690
• Recruitment Status: Completed
• First Posted: November 6, 2017
• Results First Posted: November 27, 2020
• Last Update Posted: March 18, 2022
• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo ( 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

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 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
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
Reason Not Completed
Progressive disease per RECIST	85	44	6	16	20
Clinical progression	7	4	1	1	1
Adverse Event	22	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
Miscellaneous	6	0	0	0	0
Did not receive treatment	1	0	0	1	0

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 Number of Baseline Participants		125	55	7	20	24	231
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

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.
Overall Number of Participants Analyzed	126	55	7	62
Measure Type: Count of Participants; Unit of Measure: Participants
Unconfirmed ORR, 25 months (DCO: Nov 8, 2019)	61 48.4%	7 12.7%	1 14.3%	8 12.9%
Unconfirmed ORR, 36 months (DCO: Dec 11, 2020)	61 48.4%	7 12.7%	1 14.3%	8 12.9%
Confirmed ORR, 25 months (DCO: Nov 8, 2019)	51 40.5%	6 10.9%	1 14.3%	7 11.3%
Confirmed ORR, 36 months (DCO: Dec 11, 2020)	50 39.7%	6 10.9%	1 14.3%	7 11.3%

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)
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.
Overall Number of Participants Analyzed	126	55	7	62
Measure Type: Count of Participants; Unit of Measure: Participants
Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)	11 8.7%	0 0.0%	0 0.0%	0 0.0%
Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)	10 7.9%	0 0.0%	0 0.0%	0 0.0%
Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)	50 39.7%	7 12.7%	1 14.3%	8 12.9%
Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)	51 40.5%	7 12.7%	1 14.3%	8 12.9%
Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)	46 36.5%	27 49.1%	3 42.9%	30 48.4%
Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)	47 37.3%	27 49.1%	3 42.9%	30 48.4%
Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)	15 11.9%	18 32.7%	0 0.0%	18 29.0%
Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)	15 11.9%	18 32.7%	0 0.0%	18 29.0%
Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)	4 3.2%	3 5.5%	3 42.9%	6 9.7%
Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)	3 2.4%	3 5.5%	3 42.9%	6 9.7%
Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)	10 7.9%	0 0.0%	0 0.0%	0 0.0%
Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)	9 7.1%	0 0.0%	0 0.0%	0 0.0%
Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)	41 32.5%	6 10.9%	1 14.3%	7 11.3%
Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)	41 32.5%	6 10.9%	1 14.3%	7 11.3%
Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)	55 43.7%	28 50.9%	3 42.9%	31 50.0%
Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)	57 45.2%	28 50.9%	3 42.9%	31 50.0%
Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)	15 11.9%	18 32.7%	0 0.0%	18 29.0%
Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)	15 11.9%	18 32.7%	0 0.0%	18 29.0%
Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)	5 4.0%	3 5.5%	3 42.9%	6 9.7%
Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)	4 3.2%	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)
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.
Overall Number of Participants Analyzed	126	55	7	62	21	22
Median (Full Range); Unit of Measure: months
Duration of survival follow up, 25 months (DCO: Nov 8, 2019)	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)
Duration of survival follow up, 36 months (DCO: Dec 11, 2020)	12.3; (0.4 to 33.2)	8.4; (0.3 to 29.3)	14.3; (2.0 to 22.1)	8.5; (0.3 to 29.3)	7.3; (0.2 to 27.7)	8.5; (1.8 to 23.1)
Overall survival, 25 months (DCO: Nov 8, 2019)	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)
Overall survival, 36 months (DCO: Dec 11, 2020)	12.6; (0.4 to 33.2)	8.6; (0.3 to 29.3)	14.3; (2.0 to 22.1)	8.9; (0.3 to 29.3)	7.8; (0.2 to 27.7)	8.5; (1.8 to 23.1)

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.
Overall Number of Participants Analyzed	126	55	7	62	21	22
Median (95% Confidence Interval); Unit of Measure: months
PFS, 25 months (DCO: Nov 8, 2019)	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)
PFS, 36 months (DCO: Dec 11, 2020)	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)
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.
Overall Number of Participants Analyzed		61	7	1	8	7	4
Median (Full Range); Unit of Measure: months
Unconfirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019)	Number Analyzed	61 participants	7 participants	1 participants	8 participants	7 participants	4 participants
		8.4; (0 to 21.0)	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)
Unconfirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020)	Number Analyzed	61 participants	7 participants	1 participants	8 participants	7 participants	4 participants
		11.3; (0 to 29.1)	4.1; (0 to 4.9)	3.9; (3.9 to 3.9)	3.9; (0 to 4.9)	6.8; (1.4 to 12.5)	5.8; (1.4 to 12.5)
Confirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019)	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)
Confirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020)	Number Analyzed	50 participants	6 participants	1 participants	7 participants	5 participants	2 participants
		12.7; (1.4 to 29.1)	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 12.5)	11.2; (10.0 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)
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.
Overall Number of Participants Analyzed	126	55	7	62	21	22
Measure Type: Count of Participants; Unit of Measure: Participants
DCR, 25 months (DCO: Nov 8, 2019)	107 84.9%	34 61.8%	4 57.1%	38 61.3%	17 81.0%	15 68.2%
DCR, 36 months (DCO: Dec 11, 2020)	108 85.7%	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)
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.
Overall Number of Participants Analyzed	21	22
Measure Type: Count of Participants; Unit of Measure: Participants
Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)	5 23.8%	2 9.1%
Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)	5 23.8%	2 9.1%
Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)	0 0.0%	0 0.0%
Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)	0 0.0%	0 0.0%
Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)	5 23.8%	2 9.1%
Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)	5 23.8%	2 9.1%
Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)	12 57.1%	13 59.1%
Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)	12 57.1%	13 59.1%
Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)	3 14.3%	6 27.3%
Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)	3 14.3%	6 27.3%
Inevaluable, 25 months (DCO: Nov 8, 2019)	1 4.8%	1 4.5%
Inevaluable, 36 months (DCO: Dec 11, 2020)	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)
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.
Overall Number of Participants Analyzed	125	55	7	62	20	22
Median (95% Confidence Interval); Unit of Measure: months
TTF, 25 months (DCO: Nov 8, 2019)	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)
TTF, 36 months (DCO: Dec 11, 2020)	4.3; (3.9 to 5.4)	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)
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.
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), 25 months (DCO: Nov 8, 2019)	60 50.4%	7 13.7%	1 20.0%	8 14.3%	10 52.6%	5 23.8%
Unconfirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)	60 50.4%	7 13.7%	1 20.0%	8 14.3%	10 52.6%	5 23.8%
Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)	4 3.4%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)	4 3.4%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)	56 47.1%	7 13.7%	1 20.0%	8 14.3%	10 52.6%	5 23.8%
Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)	56 47.1%	7 13.7%	1 20.0%	8 14.3%	10 52.6%	5 23.8%
Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)	42 35.3%	27 52.9%	1 20.0%	28 50.0%	7 36.8%	8 38.1%
Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)	42 35.3%	27 52.9%	1 20.0%	28 50.0%	7 36.8%	8 38.1%
Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)	15 12.6%	15 29.4%	2 40.0%	17 30.4%	2 10.5%	8 38.1%
Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)	15 12.6%	15 29.4%	2 40.0%	17 30.4%	2 10.5%	8 38.1%
Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)	2 1.7%	2 3.9%	1 20.0%	3 5.4%	0 0.0%	0 0.0%
Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)	2 1.7%	2 3.9%	1 20.0%	3 5.4%	0 0.0%	0 0.0%
Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019)	49 41.2%	5 9.8%	1 20.0%	6 10.7%	8 42.1%	3 14.3%
Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020)	51 42.9%	5 9.8%	1 20.0%	6 10.7%	8 42.1%	3 14.3%
Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019)	3 2.5%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020)	4 3.4%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019)	46 38.7%	5 9.8%	1 20.0%	6 10.7%	8 42.1%	3 14.3%
Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020)	47 39.5%	5 9.8%	1 20.0%	6 10.7%	8 42.1%	3 14.3%
Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019)	53 44.5%	28 54.9%	1 20.0%	29 51.8%	9 47.4%	10 47.6%
Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020)	51 42.9%	28 54.9%	1 20.0%	29 51.8%	9 47.4%	10 47.6%
Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019)	15 12.6%	16 31.4%	2 40.0%	18 32.1%	2 10.5%	8 38.1%
Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020)	15 12.6%	16 31.4%	2 40.0%	18 32.1%	2 10.5%	8 38.1%
Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019)	2 1.7%	2 3.9%	1 20.0%	3 5.4%	0 0.0%	0 0.0%
Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020)	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 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.
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)
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)

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.
Overall Number of Participants Analyzed		125	20	24
Mean (Standard Deviation); Unit of Measure: ng/mL
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: 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)

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.
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
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)

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.
Overall Number of Participants Analyzed		125	20	24
Mean (Standard Deviation); Unit of Measure: ng*d/mL
AUClast: MAAA-1181a, Cycle 1	Number Analyzed	125 participants	20 participants	24 participants
		46.7 (16.3)	53.4 (42.7)	44.5 (22.5)
AUClast: MAAA-1181a, Cycle 3	Number Analyzed	0 participants	0 participants	0 participants
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)

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.
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)

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.
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)

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.
Overall Number of Participants Analyzed	125	55	7	62	20	24
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE, 25 months (DCO: Nov 8, 2019)	125 100.0%	54 98.2%	7 100.0%	61 98.4%	20 100.0%	24 100.0%
Any TEAE, 36 months (DCO: Dec 11, 2020)	125 100.0%	54 98.2%	7 100.0%	61 98.4%	20 100.0%	24 100.0%
Drug-related TEAEs, 25 months (DCO: Nov 8, 2019)	122 97.6%	51 92.7%	5 71.4%	56 90.3%	19 95.0%	24 100.0%
Drug-related TEAEs, 36 months (DCO: Dec 11, 2020)	122 97.6%	51 92.7%	5 71.4%	56 90.3%	19 95.0%	24 100.0%
Serious TEAEs, 25 months (DCO: Nov 8, 2019)	55 44.0%	14 25.5%	1 14.3%	15 24.2%	6 30.0%	11 45.8%
Serious TEAEs, 36 months (DCO: Dec 11, 2020)	58 46.4%	15 27.3%	1 14.3%	16 25.8%	6 30.0%	11 45.8%
Drug-related serious TEAEs, 25 months (DCO: Nov 8, 2019)	27 21.6%	5 9.1%	0 0.0%	5 8.1%	1 5.0%	6 25.0%
Drug-related serious TEAEs, 36 months (DCO: Dec 11, 2020)	31 24.8%	5 9.1%	0 0.0%	5 8.1%	1 5.0%	6 25.0%
TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019)	19 15.2%	4 7.3%	0 0.0%	4 6.5%	2 10.0%	1 4.2%
TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020)	23 18.4%	4 7.3%	0 0.0%	4 6.5%	2 10.0%	1 4.2%
Drug-related TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019)	12 9.6%	3 5.5%	0 0.0%	3 4.8%	1 5.0%	0 0.0%
Drug-related TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020)	15 12.0%	3 5.5%	0 0.0%	3 4.8%	1 5.0%	0 0.0%
TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019)	40 32.0%	21 38.2%	0 0.0%	21 33.9%	6 30.0%	8 33.3%
TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020)	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, 25 months (DCO: Nov 8, 2019)	38 30.4%	21 38.2%	0 0.0%	21 33.9%	6 30.0%	7 29.2%
Drug-related TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020)	38 30.4%	21 38.2%	0 0.0%	21 33.9%	6 30.0%	7 29.2%
TEAEs associated with drug interrupted, 25 months (DCO: Nov 8, 2019)	78 62.4%	20 36.4%	3 42.9%	23 37.1%	8 40.0%	10 41.7%
TEAEs associated with drug interrupted, 36 months (DCO: Dec 11, 2020)	79 63.2%	20 36.4%	3 42.9%	23 37.1%	8 40.0%	10 41.7%
Drug-related TEAE associated with drug interrupted, 25 months (DCO: Nov 8, 2019)	64 51.2%	17 30.9%	2 28.6%	19 30.6%	7 35.0%	10 41.7%
Drug-related TEAE associated with drug interrupted, 36 months (DCO: Dec 11, 2020)	65 52.0%	17 30.9%	2 28.6%	19 30.6%	7 35.0%	10 41.7%
TEAEs associated with death, 25 months (DCO: Nov 8, 2019)	8 6.4%	1 1.8%	1 14.3%	2 3.2%	2 10.0%	0 0.0%
TEAEs associated with death, 36 months (DCO: Dec 11, 2020)	9 7.2%	1 1.8%	1 14.3%	2 3.2%	2 10.0%	0 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.
Overall Number of Participants Analyzed	125	55	7	62	20	24
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE, 25 months (DCO: Nov 8, 2019)	125 100.0%	54 98.2%	7 100.0%	61 98.4%	20 100.0%	24 100.0%
Any TEAE, 36 months (DCO: Dec 11, 2020)	125 100.0%	54 98.2%	7 100.0%	61 98.4%	20 100.0%	24 100.0%
Nausea, 25 months (DCO: Nov 8, 2019)	79 63.2%	27 49.1%	2 28.6%	29 46.8%	11 55.0%	19 79.2%
Nausea, 36 months (DCO: Dec 11, 2020)	79 63.2%	27 49.1%	2 28.6%	29 46.8%	11 55.0%	19 79.2%
Decreased appetite, 25 months (DCO: Nov 8, 2019)	75 60.0%	27 49.1%	1 14.3%	28 45.2%	13 65.0%	18 75.0%
Decreased appetite, 36 months (DCO: Dec 11, 2020)	76 60.8%	27 49.1%	1 14.3%	28 45.2%	13 65.0%	18 75.0%
Neutrophil count decreased, 25 months (DCO: Nov 8, 2019)	77 61.6%	18 32.7%	3 42.9%	21 33.9%	8 40.0%	12 50.0%
Neutrophil count decreased, 36 months (DCO: Dec 11, 2020)	79 63.2%	18 32.7%	3 42.9%	21 33.9%	8 40.0%	12 50.0%
Anaemia, 25 months (DCO: Nov 8, 2019)	71 56.8%	17 30.9%	2 28.6%	19 30.6%	10 50.0%	10 41.7%
Anaemia, 36 months (DCO: Dec 11, 2020)	71 56.8%	17 30.9%	2 28.6%	19 30.6%	10 50.0%	11 45.8%
White blood cell count decreased, 25 months (DCO: Nov 8, 2019)	47 37.6%	18 32.7%	3 42.9%	21 33.9%	4 20.0%	7 29.2%
White blood cell count decreased, 36 months (DCO: Dec 11, 2020)	49 39.2%	18 32.7%	3 42.9%	21 33.9%	4 20.0%	7 29.2%
Platelet count decreased, 25 months (DCO: Nov 8, 2019)	47 37.6%	4 7.3%	0 0.0%	4 6.5%	3 15.0%	7 29.2%
Platelet count decreased, 36 months (DCO: Dec 11, 2020)	48 38.4%	4 7.3%	0 0.0%	4 6.5%	3 15.0%	7 29.2%
Malaise, 25 months (DCO: Nov 8, 2019)	43 34.4%	9 16.4%	1 14.3%	10 16.1%	4 20.0%	9 37.5%
Malaise, 36 months (DCO: Dec 11, 2020)	44 35.2%	9 16.4%	1 14.3%	10 16.1%	4 20.0%	9 37.5%
Diarrhoea, 25 months (DCO: Nov 8, 2019)	40 32.0%	20 36.4%	0 0.0%	20 32.3%	6 30.0%	8 33.3%
Diarrhoea, 36 months (DCO: Dec 11, 2020)	41 32.8%	20 36.4%	0 0.0%	20 32.3%	6 30.0%	8 33.3%
Vomiting, 25 months (DCO: Nov 8, 2019)	33 26.4%	5 9.1%	0 0.0%	5 8.1%	4 20.0%	7 29.2%
Vomiting, 36 months (DCO: Dec 11, 2020)	33 26.4%	5 9.1%	0 0.0%	5 8.1%	4 20.0%	7 29.2%
Constipation, 25 months (DCO: Nov 8, 2019)	30 24.0%	13 23.6%	1 14.3%	14 22.6%	5 25.0%	5 20.8%
Constipation, 36 months (DCO: Dec 11, 2020)	31 24.8%	13 23.6%	2 28.6%	15 24.2%	5 25.0%	5 20.8%
Pyrexia, 25 months (DCO: Nov 8, 2019)	30 24.0%	8 14.5%	2 28.6%	10 16.1%	3 15.0%	6 25.0%
Pyrexia, 36 months (DCO: Dec 11, 2020)	31 24.8%	8 14.5%	2 28.6%	10 16.1%	3 15.0%	6 25.0%
Fatigue, 25 months (DCO: Nov 8, 2019)	27 21.6%	15 27.3%	0 0.0%	15 24.2%	5 25.0%	6 25.0%
Fatigue, 36 months (DCO: Dec 11, 2020)	27 21.6%	15 27.3%	0 0.0%	15 24.2%	5 25.0%	6 25.0%
Alopecia, 25 months (DCO: Nov 8, 2019)	28 22.4%	8 14.5%	1 14.3%	9 14.5%	3 15.0%	1 4.2%
Alopecia, 36 months (DCO: Dec 11, 2020)	28 22.4%	8 14.5%	1 14.3%	9 14.5%	3 15.0%	1 4.2%
Lymphocyte count decreased, 25 months (DCO: Nov 8, 2019)	27 21.6%	2 3.6%	0 0.0%	2 3.2%	1 5.0%	3 12.5%
Lymphocyte count decreased, 36 months (DCO: Dec 11, 2020)	30 24.0%	2 3.6%	0 0.0%	2 3.2%	1 5.0%	3 12.5%
Weight decreased, 25 months (DCO: Nov 8, 2019)	17 13.6%	5 9.1%	0 0.0%	5 8.1%	4 20.0%	7 29.2%
Weight decreased, 36 months (DCO: Dec 11, 2020)	19 15.2%	5 9.1%	0 0.0%	5 8.1%	4 20.0%	7 29.2%
Hypoalbuminaemia, 25 months (DCO: Nov 8, 2019)	18 14.4%	7 12.7%	1 14.3%	8 12.9%	2 10.0%	5 20.8%
Hypoalbuminaemia, 36 months (DCO: Dec 11, 2020)	18 14.4%	7 12.7%	1 14.3%	8 12.9%	2 10.0%	5 20.8%
Oedema peripheral, 25 months (DCO: Nov 8, 2019)	13 10.4%	0 0.0%	0 0.0%	0 0.0%	4 20.0%	1 4.2%
Oedema peripheral, 36 months (DCO: Dec 11, 2020)	15 12.0%	0 0.0%	0 0.0%	0 0.0%	4 20.0%	2 8.3%
Dysgeusia, 25 months (DCO: Nov 8, 2019)	9 7.2%	4 7.3%	0 0.0%	4 6.5%	4 20.0%	1 4.2%
Dysgeusia, 36 months (DCO: Dec 11, 2020)	9 7.2%	4 7.3%	0 0.0%	4 6.5%	4 20.0%	1 4.2%
Peripheral sensory neuropathy, 25 months (DCO: Nov 8, 2019)	4 3.2%	0 0.0%	2 28.6%	2 3.2%	2 10.0%	0 0.0%
Peripheral sensory neuropathy, 36 months (DCO: Dec 11, 2020)	4 3.2%	0 0.0%	2 28.6%	2 3.2%	2 10.0%	0 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 (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	98/125 (78.40%)	46/55 (83.64%)	4/7 (57.14%)	50/62 (80.65%)	16/20 (80.00%)	21/24 (87.50%)
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	58/125 (46.40%)	15/55 (27.27%)	1/7 (14.29%)	16/62 (25.81%)	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%)
Eye disorders
Cataract † 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%)
Glaucoma † 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%)	1/55 (1.82%)	0/7 (0.00%)	1/62 (1.61%)	1/20 (5.00%)	1/24 (4.17%)
Cholangitis † 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%)
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	1/125 (0.80%)	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	5/125 (4.00%)	0/55 (0.00%)	0/7 (0.00%)	0/62 (0.00%)	0/20 (0.00%)	0/24 (0.00%)
Interstitial lung disease † 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%)
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
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%)	11/24 (45.83%)
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	41/125 (32.80%)	20/55 (36.36%)	0/7 (0.00%)	20/62 (32.26%)	6/20 (30.00%)	8/24 (33.33%)
Constipation † 1	31/125 (24.80%)	13/55 (23.64%)	2/7 (28.57%)	15/62 (24.19%)	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	14/125 (11.20%)	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	8/125 (6.40%)	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%)
Periodontal disease † 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%)
General disorders
Malaise † 1	44/125 (35.20%)	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	31/125 (24.80%)	8/55 (14.55%)	2/7 (28.57%)	10/62 (16.13%)	3/20 (15.00%)	6/24 (25.00%)
Oedema peripheral † 1	15/125 (12.00%)	0/55 (0.00%)	0/7 (0.00%)	0/62 (0.00%)	4/20 (20.00%)	2/24 (8.33%)
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%)	1/55 (1.82%)	0/7 (0.00%)	1/62 (1.61%)	1/20 (5.00%)	1/24 (4.17%)
Infections and infestations
Nasopharyngitis † 1	11/125 (8.80%)	4/55 (7.27%)	1/7 (14.29%)	5/62 (8.06%)	1/20 (5.00%)	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	6/125 (4.80%)	0/55 (0.00%)	0/7 (0.00%)	0/62 (0.00%)	2/20 (10.00%)	1/24 (4.17%)
Influenza † 1	4/125 (3.20%)	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	1/125 (0.80%)	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%)
Procedural pain † 1	1/125 (0.80%)	0/55 (0.00%)	1/7 (14.29%)	1/62 (1.61%)	1/20 (5.00%)	0/24 (0.00%)
Investigations
Neutrophil count decreased † 1	79/125 (63.20%)	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	49/125 (39.20%)	18/55 (32.73%)	3/7 (42.86%)	21/62 (33.87%)	4/20 (20.00%)	7/24 (29.17%)
Platelet count decreased † 1	48/125 (38.40%)	4/55 (7.27%)	0/7 (0.00%)	4/62 (6.45%)	3/20 (15.00%)	7/24 (29.17%)
Lymphocyte count decreased † 1	30/125 (24.00%)	2/55 (3.64%)	0/7 (0.00%)	2/62 (3.23%)	1/20 (5.00%)	3/24 (12.50%)
Weight decreased † 1	19/125 (15.20%)	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	11/125 (8.80%)	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%)	2/20 (10.00%)	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%)
Lymphocyte count 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%)
Metabolism and nutrition disorders
Decreased appetite † 1	76/125 (60.80%)	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	11/125 (8.80%)	4/55 (7.27%)	0/7 (0.00%)	4/62 (6.45%)	0/20 (0.00%)	4/24 (16.67%)
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	10/125 (8.00%)	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	2/125 (1.60%)	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	6/125 (4.80%)	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%)
Brain oedema † 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	1/125 (0.80%)	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	11/125 (8.80%)	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%)
Interstitial lung disease † 1	8/125 (6.40%)	0/55 (0.00%)	0/7 (0.00%)	0/62 (0.00%)	1/20 (5.00%)	1/24 (4.17%)
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	10/125 (8.00%)	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	9/125 (7.20%)	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	2/125 (1.60%)	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

Limitations and 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

Publications of Results:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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

• Responsible Party: Daiichi Sankyo ( 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: March 18, 2022