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DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer (DESTINY-Lung01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03505710
Recruitment Status : Active, not recruiting
First Posted : April 23, 2018
Results First Posted : May 17, 2022
Last Update Posted : January 20, 2023
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Intervention Drug: Trastuzumab deruxtecan
Enrollment 181
Recruitment Details A total of 181 participants were enrolled and treated at clinic centers in Japan, United States, France, Netherlands, and Spain. Primary results reported is from baseline up to data cut-off date of 03 May 2021. The results presented are based on primary analysis up to 36 months. Data collection is still on-going and additional results will be provided after study completion.
Pre-assignment Details Duration of follow-up (months) was defined as ((last visit date - enrollment date + 1)/365.25) × 12. Last visit date was the date of last clinical visit for ongoing participants, date of death for participants who died, or the last known contact date in survival follow-up for other participants who discontinued study drug.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC to who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Period Title: Overall Study
Started 49 41 91
Completed [1] 2 14 15
Not Completed 47 27 76
Reason Not Completed
Progressive Disease             22             9             34
Clinical Progression             6             6             3
Adverse Event             12             5             27
Withdrawal by Subject             1             3             3
Physician Decision             1             0             2
Death             4             3             6
Other Reasons             1             1             1
[1]
Completed = Participants ongoing treatment as of 03 May 2021, Not Completed = Participants who discontinued treatment
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated Total
Hide Arm/Group Description

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC to who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

 Total of all reporting groups
Overall Number of Baseline Participants 49 41 91 181
Hide Baseline Analysis Population Description
Baseline characteristics were assessed using the Safety Analysis Set.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 41 participants 91 participants 181 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
27
  55.1%
27
  65.9%
55
  60.4%
109
  60.2%
>=65 years
22
  44.9%
14
  34.1%
36
  39.6%
72
  39.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants 41 participants 91 participants 181 participants
62.2  (9.58) 60.3  (10.22) 60.3  (11.94) 60.8  (10.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 41 participants 91 participants 181 participants
Female
19
  38.8%
19
  46.3%
60
  65.9%
98
  54.1%
Male
30
  61.2%
22
  53.7%
31
  34.1%
83
  45.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 41 participants 91 participants 181 participants
American Indian or Alaska Native
0
   0.0%
1
   2.4%
0
   0.0%
1
   0.6%
Asian
13
  26.5%
4
   9.8%
31
  34.1%
48
  26.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   8.2%
2
   4.9%
1
   1.1%
7
   3.9%
White
31
  63.3%
31
  75.6%
40
  44.0%
102
  56.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   2.0%
3
   7.3%
19
  20.9%
23
  12.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 49 participants 41 participants 91 participants 181 participants
Netherlands 10 8 13 31
United States 19 13 35 67
Japan 12 3 23 38
France 0 3 15 18
Spain 8 14 5 27
1.Primary Outcome
Title Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
Hide Description The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee 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. Confirmed ORR based on ICR is reported.
Time Frame Up to 36 months (data cut-off)
Hide Outcome Measure Data
Hide Analysis Population Description
Objective response rate was assessed in the Full Analysis Set at data cut-off date of 03 May 2021.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description:

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Overall Number of Participants Analyzed 49 41 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
26.5
(15.0 to 41.1)
29.3
(16.1 to 45.5)
54.9
(44.2 to 65.4)
2.Secondary Outcome
Title Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
Hide Description The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment 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. Confirmed ORR based on investigator assessment is reported.
Time Frame Up to 36 months (data cut-off)
Hide Outcome Measure Data
Hide Analysis Population Description
Objective response rate was assessed in the Full Analysis Set at data cut-off date of 03 May 2021.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description:

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Overall Number of Participants Analyzed 49 41 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
28.6
(16.6 to 43.3)
31.7
(18.1 to 48.1)
61.5
(50.8 to 71.6)
3.Secondary Outcome
Title Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
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 in participants with confirmed CR/PR based on independent central review and investigator assessment is reported.
Time Frame Up to 36 months (data cut-off)
Hide Outcome Measure Data
Hide Analysis Population Description
Duration of Response (DoR) was assessed in the Full Analysis Set of participants with confirmed CR/PR at data cut-off date of 03 May 2021.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description:

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Overall Number of Participants Analyzed 13 12 50
Median (95% Confidence Interval)
Unit of Measure: months
Independent Central Review Number Analyzed 13 participants 12 participants 50 participants
5.8 [1] 
(4.3 to NA)
4.7 [1] 
(4.0 to NA)
9.3
(5.7 to 14.7)
Investigator Assessment Number Analyzed 11 participants 3 participants 30 participants
5.8
(4.7 to 11.3)
7.0 [1] 
(4.2 to NA)
11.7
(7.2 to 16.9)
[1]
Upper limit of 95% Confidence Interval (CI) was not estimable due to insufficient number of events.
4.Secondary Outcome
Title Progression-Free Survival (PFS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
Hide Description Progression-free survival (PFS) was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. PFS based on independent central review and investigator assessment is reported.
Time Frame Up to 36 months (data cut-off)
Hide Outcome Measure Data
Hide Analysis Population Description
Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 03 May 2021.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description:

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Overall Number of Participants Analyzed 49 41 91
Median (95% Confidence Interval)
Unit of Measure: months
Independent Central Review
5.7
(2.8 to 7.2)
6.7 [1] 
(4.5 to NA)
8.2
(6.0 to 11.9)
Investigator Assessment
5.7
(3.8 to 7.2)
7.2
(4.1 to 8.4)
9.3
(7.1 to 14.0)
[1]
Upper limit of 95% Confidence Interval (CI) was not estimable due to insufficient number of events.
5.Secondary Outcome
Title Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
Hide Description Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.
Time Frame Up to 36 months (data cut-off)
Hide Outcome Measure Data
Hide Analysis Population Description
Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 03 May 2021.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description:

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Overall Number of Participants Analyzed 49 41 91
Median (95% Confidence Interval)
Unit of Measure: months
12.4
(7.8 to 17.2)
NA [1] 
(6.7 to NA)
17.8
(13.8 to 22.1)
[1]
Median OS and upper limit of 95% Confidence Interval (CI) was not estimable due to insufficient number of events.
6.Secondary Outcome
Title Percentage of Participants With Disease Control Rate (DCR) Following Treatment With DS8201a in Participants With HER2-Over-Expressing or -Mutated Non-Small-Cell Lung Cancer (NSCLC)
Hide Description Disease Control Rate (DCR) was defined as the percentage of participants who achieved a best overall response of CR, PR, or stable disease (SD) during study treatment. Confirmation of CR/PR was required. DCR based on independent central review and investigator assessment is reported.
Time Frame Up to 36 months (data cut-off)
Hide Outcome Measure Data
Hide Analysis Population Description
Disease control rate was assessed in the Full Analysis Set at data cut-off date of 03 May 2021.
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description:

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
Overall Number of Participants Analyzed 49 41 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Independent Central Review
68.9
(53.4 to 81.8)
77.5
(61.6 to 89.2)
93.0
(85.4 to 97.4)
Investigator Assessment
75.5
(61.1 to 86.7)
78.0
(62.4 to 89.4)
94.5
(87.6 to 98.2)
Time Frame Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up 36 months.
Adverse Event Reporting Description A Treatment-emergent adverse event (TEAE) is defined as an 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.
 
Arm/Group Title Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Hide Arm/Group Description

Participants with HER2-overexpressing(immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-overexpressing (immunohistochemistry [IHC] 3+ or IHC 2+), unresectable and/or metastatic NSCLC adenocarcinoma who received 5.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.

Participants with HER2-mutated, unresectable and/or metastatic NSCLC who received 6.4 mg/kg trastuzumab deruxtecan (DS-8201a).

Trastuzumab deruxtecan: Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
All-Cause Mortality
Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   35/49 (71.43%)   11/41 (26.83%)   47/91 (51.65%) 
Hide Serious Adverse Events
Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   27/49 (55.10%)   14/41 (34.15%)   39/91 (42.86%) 
Blood and lymphatic system disorders       
Thrombocytopenia † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Cardiac disorders       
Myocardial Infarction † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Pericardial Effusion † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Gastrointestinal disorders       
Vomiting † 1  1/49 (2.04%)  1/41 (2.44%)  3/91 (3.30%) 
Diarrhoea † 1  1/49 (2.04%)  1/41 (2.44%)  1/91 (1.10%) 
Nausea † 1  2/49 (4.08%)  0/41 (0.00%)  1/91 (1.10%) 
Duodenal Stenosis † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Duodenal Ulcer Haemorrhage † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Gastrointestinal Motility Disorder † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Haemorrhoids † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Ileus † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Intestinal Obstruction † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Intestinal Perforation † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Intra-Abdominal Haematoma † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Oesophageal Obstruction † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Rectal Haemorrhage † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Small Intestinal Haemorrhage † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Small Intestinal Obstruction † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Upper Gastrointestinal Haemorrhage † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
General disorders       
Disease Progression † 1  6/49 (12.24%)  3/41 (7.32%)  7/91 (7.69%) 
Asthenia † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Fatigue † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Non-Cardiac Chest Pain † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Oedema Peripheral † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Pain † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Pyrexia † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Hepatobiliary disorders       
Cholangitis † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Infections and infestations       
Pneumonia † 1  4/49 (8.16%)  1/41 (2.44%)  2/91 (2.20%) 
Respiratory Tract Infection † 1  1/49 (2.04%)  1/41 (2.44%)  0/91 (0.00%) 
Abdominal Sepsis † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Bacteraemia † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Cellulitis † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Covid-19 Pneumonia † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Empyema † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Enterocolitis Infectious † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Oesophageal Infection † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Pneumocystis Jirovecii Pneumonia † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Pneumonia Staphylococcal † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Sepsis † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Septic Shock † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Staphylococcal Bacteraemia † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Urinary Tract Infection † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Injury, poisoning and procedural complications       
Fall † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Radiation Necrosis † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Transfusion Reaction † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Investigations       
Electrocardiogram T Wave Abnormal † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Troponin I Increased † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Troponin Increased † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Musculoskeletal and connective tissue disorders       
Bone Pain † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Osteoarthritis † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasm Malignant † 1  0/49 (0.00%)  1/41 (2.44%)  0/91 (0.00%) 
Nervous system disorders       
Seizure † 1  1/49 (2.04%)  0/41 (0.00%)  3/91 (3.30%) 
Central Nervous System Necrosis † 1  0/49 (0.00%)  0/41 (0.00%)  2/91 (2.20%) 
Ataxia † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Hepatic Encephalopathy † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Hydrocephalus † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Partial Seizures † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Presyncope † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Syncope † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Psychiatric disorders       
Mental Status Changes † 1  1/49 (2.04%)  0/41 (0.00%)  1/91 (1.10%) 
Confusional State † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Delirium † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Renal and urinary disorders       
Acute Kidney Injury † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pneumonitis † 1  4/49 (8.16%)  1/41 (2.44%)  7/91 (7.69%) 
Dyspnoea † 1  4/49 (8.16%)  1/41 (2.44%)  1/91 (1.10%) 
Hypoxia † 1  0/49 (0.00%)  2/41 (4.88%)  1/91 (1.10%) 
Interstitial Lung Disease † 1  0/49 (0.00%)  0/41 (0.00%)  3/91 (3.30%) 
Pleural Effusion † 1  0/49 (0.00%)  1/41 (2.44%)  2/91 (2.20%) 
Acute Pulmonary Oedema † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Bronchospasm † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Haemoptysis † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Pulmonary Oedema † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Respiratory Failure † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
Wheezing † 1  0/49 (0.00%)  0/41 (0.00%)  1/91 (1.10%) 
Vascular disorders       
Hypotension † 1  1/49 (2.04%)  1/41 (2.44%)  0/91 (0.00%) 
Deep Vein Thrombosis † 1  1/49 (2.04%)  0/41 (0.00%)  0/91 (0.00%) 
1
Term from vocabulary, MedDRA (23.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: HER2 Overexpressing Cohort 1a: HER2 Overexpressing Cohort 2: HER2 Mutated
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   46/49 (93.88%)   41/41 (100.00%)   91/91 (100.00%) 
Blood and lymphatic system disorders       
Anaemia † 1  14/49 (28.57%)  10/41 (24.39%)  32/91 (35.16%) 
Neutropenia † 1  3/49 (6.12%)  2/41 (4.88%)  6/91 (6.59%) 
Eye disorders       
Dry Eye † 1  0/49 (0.00%)  2/41 (4.88%)  7/91 (7.69%) 
Gastrointestinal disorders       
Nausea † 1  28/49 (57.14%)  30/41 (73.17%)  68/91 (74.73%) 
Diarrhoea † 1  13/49 (26.53%)  13/41 (31.71%)  37/91 (40.66%) 
Vomiting † 1  13/49 (26.53%)  12/41 (29.27%)  41/91 (45.05%) 
Constipation † 1  15/49 (30.61%)  10/41 (24.39%)  34/91 (37.36%) 
Abdominal Pain † 1  2/49 (4.08%)  5/41 (12.20%)  8/91 (8.79%) 
Stomatitis † 1  6/49 (12.24%)  1/41 (2.44%)  6/91 (6.59%) 
Gastrooesophageal Reflux Disease † 1  2/49 (4.08%)  1/41 (2.44%)  8/91 (8.79%) 
Dyspepsia † 1  0/49 (0.00%)  2/41 (4.88%)  6/91 (6.59%) 
Dysphagia † 1  3/49 (6.12%)  0/41 (0.00%)  5/91 (5.49%) 
Abdominal Pain Ulcer † 1  3/49 (6.12%)  0/41 (0.00%)  4/91 (4.40%) 
Haemorrhoids † 1  0/49 (0.00%)  0/41 (0.00%)  7/91 (7.69%) 
Haemorrhoidal Haemorrhage † 1  0/49 (0.00%)  0/41 (0.00%)  5/91 (5.49%) 
Fatigue † 1  16/49 (32.65%)  20/41 (48.78%)  30/91 (32.97%) 
General disorders       
Asthenia † 1  6/49 (12.24%)  6/41 (14.63%)  16/91 (17.58%) 
Malaise † 1  9/49 (18.37%)  3/41 (7.32%)  12/91 (13.19%) 
Pyrexia † 1  1/49 (2.04%)  1/41 (2.44%)  16/91 (17.58%) 
Oedema Peripheral † 1  2/49 (4.08%)  4/41 (9.76%)  11/91 (12.09%) 
Non-Cardiac Chest Pain † 1  3/49 (6.12%)  4/41 (9.76%)  3/91 (3.30%) 
Infections and infestations       
Pneumonia † 1  5/49 (10.20%)  1/41 (2.44%)  15/91 (16.48%) 
Urinary Tract Infection † 1  3/49 (6.12%)  2/41 (4.88%)  9/91 (9.89%) 
Investigations       
Neutrophil Count Decreased † 1  11/49 (22.45%)  2/41 (4.88%)  27/91 (29.67%) 
White Blood Cell Count Decreased † 1  6/49 (12.24%)  1/41 (2.44%)  17/91 (18.68%) 
Lymphocyte Count Decreased † 1  5/49 (10.20%)  1/41 (2.44%)  13/91 (14.29%) 
Weight Decreased † 1  12/49 (24.49%)  6/41 (14.63%)  21/91 (23.08%) 
Alanine Aminotransferase Increased † 1  5/49 (10.20%)  3/41 (7.32%)  14/91 (15.38%) 
Aspartate Aminotransferase Increased † 1  6/49 (12.24%)  2/41 (4.88%)  17/91 (18.68%) 
Platelet Count Decreased † 1  7/49 (14.29%)  2/41 (4.88%)  11/91 (12.09%) 
Blood Creatinine Increased † 1  5/49 (10.20%)  3/41 (7.32%)  4/91 (4.40%) 
Blood Alkaline Phosphatase Increased † 1  3/49 (6.12%)  1/41 (2.44%)  5/91 (5.49%) 
Electrocardiogram Qt Prolonged † 1  0/49 (0.00%)  0/41 (0.00%)  6/91 (6.59%) 
Metabolism and nutrition disorders       
Decreased Appetite † 1  22/49 (44.90%)  19/41 (46.34%)  32/91 (35.16%) 
Hypokalaemia † 1  8/49 (16.33%)  3/41 (7.32%)  11/91 (12.09%) 
Hypomagnesaemia † 1  4/49 (8.16%)  1/41 (2.44%)  4/91 (4.40%) 
Dehydration † 1  2/49 (4.08%)  3/41 (7.32%)  2/91 (2.20%) 
Hypoalbuminaemia † 1  1/49 (2.04%)  1/41 (2.44%)  7/91 (7.69%) 
Hyponatraemia † 1  2/49 (4.08%)  3/41 (7.32%)  4/91 (4.40%) 
Musculoskeletal and connective tissue disorders       
Back Pain † 1  2/49 (4.08%)  5/41 (12.20%)  15/91 (16.48%) 
Arthralgia † 1  3/49 (6.12%)  0/41 (0.00%)  12/91 (13.19%) 
Myalgia † 1  3/49 (6.12%)  0/41 (0.00%)  6/91 (6.59%) 
Muscluar Weakness † 1  0/49 (0.00%)  2/41 (4.88%)  5/91 (5.49%) 
Muscle Spasms † 1  3/49 (6.12%)  2/41 (4.88%)  2/91 (2.20%) 
Pain in Extremity † 1  0/49 (0.00%)  3/41 (7.32%)  2/91 (2.20%) 
Nervous system disorders       
Dizziness † 1  10/49 (20.41%)  3/41 (7.32%)  8/91 (8.79%) 
Headache † 1  3/49 (6.12%)  2/41 (4.88%)  15/91 (16.48%) 
Dysgeusia † 1  4/49 (8.16%)  3/41 (7.32%)  12/91 (13.19%) 
Peripheral Sensory Neuropathy † 1  1/49 (2.04%)  0/41 (0.00%)  5/91 (5.49%) 
Psychiatric disorders       
Insomnia † 1  2/49 (4.08%)  0/41 (0.00%)  12/91 (13.19%) 
Anxiety † 1  1/49 (2.04%)  3/41 (7.32%)  8/91 (8.79%) 
Depression † 1  0/49 (0.00%)  0/41 (0.00%)  5/91 (5.49%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea † 1  9/49 (18.37%)  8/41 (19.51%)  17/91 (18.68%) 
Cough † 1  6/49 (12.24%)  11/41 (26.83%)  14/91 (15.38%) 
Pneumonitis † 1  4/49 (8.16%)  1/41 (2.44%)  12/91 (13.19%) 
Epistaxis † 1  4/49 (8.16%)  3/41 (7.32%)  8/91 (8.79%) 
Hiccups † 1  4/49 (8.16%)  2/41 (4.88%)  4/91 (4.40%) 
Productive Cough † 1  0/49 (0.00%)  2/41 (4.88%)  5/91 (5.49%) 
Rhinorrhoea † 1  3/49 (6.12%)  1/41 (2.44%)  1/91 (1.10%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1  10/49 (20.41%)  5/41 (12.20%)  42/91 (46.15%) 
Dry Skin † 1  1/49 (2.04%)  0/41 (0.00%)  11/91 (12.09%) 
Pruritus † 1  1/49 (2.04%)  1/41 (2.44%)  6/91 (6.59%) 
Rash Maculo-Papular † 1  0/49 (0.00%)  0/41 (0.00%)  6/91 (6.59%) 
Eczema † 1  0/49 (0.00%)  0/41 (0.00%)  5/91 (5.49%) 
Vascular disorders       
Hypertension † 1  0/49 (0.00%)  0/41 (0.00%)  5/91 (5.49%) 
Hypotension † 1  4/49 (8.16%)  0/41 (0.00%)  0/91 (0.00%) 
1
Term from vocabulary, MedDRA (23.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03505710    
Other Study ID Numbers: DS8201-A-U204
2017-004781-94 ( EudraCT Number )
JapicCTI-183916 ( Registry Identifier: JAPIC )
First Submitted: April 13, 2018
First Posted: April 23, 2018
Results First Submitted: April 25, 2022
Results First Posted: May 17, 2022
Last Update Posted: January 20, 2023