A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03248492
• Collaborator: AstraZeneca (Industry), Daiichi Sankyo Co., Ltd. (Industry)
• Enrollment: 253
• Locations: 99
• Arms: 4
• Anticipated Duration (Months): 73.2
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: DS-8201a	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 253 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
• Masking: None (Open Label)
• Masking Description: In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)
• Actual Study Start Date: Aug 25, 2017
• Actual Primary Completion Date: Mar 21, 2019
• Anticipated Study Completion Date: Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DS-8201a Low Dose T-DM1 resistant/refractory (R/R) patients in the low dose treatment group	Drug: DS-8201a; DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.; Other Names: Experimental product
Experimental: DS-8201a Medium Dose T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group	Drug: DS-8201a; DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.; Other Names: Experimental product
Experimental: DS-8201a High Dose T-DM1 resistant/refractory (R/R) patients in the high dose treatment group	Drug: DS-8201a; DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.; Other Names: Experimental product
Other: Exploratory Arm In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm	Drug: DS-8201a; DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.; Other Names: Experimental product

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)]

   The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.

Secondary Outcome Measures

1. Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)]

   The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.

2. Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)]

   Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.

3. Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)]

   Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.

4. Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)]

   The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.

5. Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)]

   The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.

6. Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) [Baseline up to Week 6, 12, 18, 24, 30, 36 post dose]

   Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.

7. Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) [Day 0 to Day 47 post last dose]

   TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women the age of majority in their country

• Has pathologically documented breast cancer that:

1. is unresectable or metastatic

2. has HER2 positive expression confirmed per protocol

• Has an adequate tumor sample

• Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

• Has protocol-defined adequate cardiac, renal and hepatic function

• Agrees to follow protocol-defined method(s) of contraception

Exclusion Criteria:

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

• Has a corrected QT interval (QTc) prolongation to > 450 millisecond (ms) in males and

470 ms in females

• Has a medical history of clinically significant lung disease

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

• Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:

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

2. safety of study staff

3. analysis of results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Urological Institute dba Alaska Clinical Research Center	Anchorage	Alaska	United States	99508
2	Arizona Oncology Associates	Tucson	Arizona	United States	85704
3	The Regents of the University of California	Los Angeles	California	United States	90095
4	Sharp Clinical Oncology Research	San Diego	California	United States	92123
5	University of California San Francisco	San Francisco	California	United States	94115
6	Sansum Clinic	Santa Barbara	California	United States	93105
7	Innovative Clinical Research Institute, LLC	Whittier	California	United States	90603
8	Sylvester Comprehensive Cancer Center - Deerfield Beach	Boca Raton	Florida	United States	33426
9	Specialist Global Research	Hialeah	Florida	United States	33012
10	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida	United States	33176
11	Piedmont Cancer Institute	Atlanta	Georgia	United States	30318
12	Straub Medical Center	Honolulu	Hawaii	United States	96813
13	University of Hawaii	Honolulu	Hawaii	United States	96813
14	Norton Healthcare	Louisville	Kentucky	United States	40202
15	University of Louisville Research Foundation	Louisville	Kentucky	United States	40202
16	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70120
17	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
18	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
19	Henry Ford Hospital	Detroit	Michigan	United States	48202
20	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
21	North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists	East Setauket	New York	United States	11733
22	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
23	Aultman Hospital Cancer Center	Canton	Ohio	United States	44710
24	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
25	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
26	UPMC Cancer Center	Pittsburgh	Pennsylvania	United States	15232
27	St Francis Hospital	Greenville	South Carolina	United States	29601
28	Accurate Clinical Research	Baytown	Texas	United States	77521
29	Texas Oncology, P.A.	Dallas	Texas	United States	75246
30	Texas Oncology - Memorial City	Houston	Texas	United States	77024
31	MD Anderson Cancer Center	Houston	Texas	United States	77030
32	The Methodist Hospital Research Institute	Houston	Texas	United States	77030
33	Texas Oncology, P.A. - Longview	Tyler	Texas	United States	75702
34	The University of Texas Health Science Center at Tyler	Tyler	Texas	United States	75708
35	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
36	Providence Regional Medical Center - Everett	Everett	Washington	United States	98201
37	Imeldaziekenhuis	Bonheiden		Belgium	2820
38	Grand Hôpital de Charleroi	Charleroi		Belgium	6000
39	UZ Leuven	Leuven		Belgium	3000
40	CHU Sart Tilman	Liège		Belgium	4000
41	AZ Sint-Maarten	Mechelen		Belgium	2800
42	University of Calgary	Calgary	Alberta	Canada	T2N 4N2
43	Institut Sainte Catherine	Avignon		France	84918
44	CHU Besançon - Hôpital Jean Minjoz	Besançon		France	25030
45	Centre Georges François Leclerc	Dijon		France	21079
46	CHU Bordeaux - Hôpital Saint André	Gironde		France	33075
47	CH de la Rochelle - Hopital St Louis	La Rochelle		France	17019
48	Clinique Victor Hugo - Centre Jean Bernard	Le Mans		France	72015
49	Hôpital Nord - CHU Marseille	Marseille		France	13915
50	Institut Régional du Cancer de Montpellier	Montpellier		France	34298
51	Centre Catherine de Sienne	Nantes		France	44202
52	Hôpital Saint-Louis - Paris	Paris		France	75475
53	Centre Hospitalier Lyon Sud	Pierre-Bénite		France	69495
54	CRLCC Eugene Marquis	Rennes		France	35042
55	Hôpital d'Instruction des Armees Begin	Saint-Mandé		France	94160
56	Centre Paul Strauss	Strasbourg		France	67000
57	Institut Gustave Roussy	Villejuif		France	94805
58	Ospedale San Raffaele	Milano		Italy	20132
59	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
60	IEO Istituto Europeo di Oncologia	Milano		Italy	20141
61	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza		Italy	20900
62	Ospedale degli Infermi	Rimini		Italy	47923
63	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Torrette		Italy	60020
64	NHO Shikoku Cancer Center	Matsuyama	Ehime-Ken	Japan	791-0280
65	Toranomon Hospital	Minato-Ku	Tokyo-To	Japan	105-8470
66	Aichi Cancer Center Hospital	Aichi		Japan	464-8681
67	National Cancer Center Hospital East	Chiba		Japan	277-8577
68	NHO Kyushu Cancer Center	Fukuoka		Japan	811-1395
69	Hakuaikai Sagara Hospital	Kagoshima		Japan	892-0833
70	Kanagawa Cancer Center	Kanagawa		Japan	241-0815
71	Kindai University Hospital	Osaka		Japan	589-8511
72	National Cancer Center Hospital	Tokyo		Japan	104-0045
73	St. Luke's International Hospital	Tokyo		Japan	104-8560
74	Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
75	Kyungpook National University Chilgok Hospital	Daegu		Korea, Republic of	41404
76	National Cancer Center	Goyang-si		Korea, Republic of	10408
77	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13620
78	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
79	Seoul National University Hospital	Seoul		Korea, Republic of	03080
80	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	03722
81	Asan Medical Center	Seoul		Korea, Republic of	05505
82	Samsung Medical Center	Seoul		Korea, Republic of	06351
83	Hospital Infanta Cristina	Badajoz		Spain	6080
84	Hospital Universitari Quiron Dexeus	Barcelona		Spain	08028
85	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
86	ICO l´Hospitalet - Hospital Duran i Reynals	Barcelona		Spain	08908
87	Hospital Quiron Barcelona	Barcelona		Spain	8023
88	MD Anderson Cancer Centre	Madrid		Spain	28033
89	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
90	Hospital Universitario La Paz	Madrid		Spain	28046
91	Hospital Clinico Universitario Virgen de la Victoria	Málaga		Spain	29010
92	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
93	Instituto Valenciano de Oncologia IVO	Valencia		Spain	46009
94	Derriford Hospital	Plymouth	Devon	United Kingdom	PL6 8BQ
95	Queen Mary University of London	London	Greater London	United Kingdom	EC1M 6BQ
96	University College London Hospitals	London	Greater London	United Kingdom	NW1 2PG
97	Western General Hospital	Edinburgh	Lothian Region	United Kingdom	EH4 2XU
98	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
99	Royal Surrey County Hospital	Guildford	Surrey	United Kingdom	GU2 7XX

Sponsors and Collaborators

• Daiichi Sankyo, Inc.
• AstraZeneca
• Daiichi Sankyo Co., Ltd.

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 26, 2019

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT03248492
• Other Study ID Numbers: DS8201-A-U201; 2016-004986-18; JapicCTI-173693(en); DESTINY-Breast01
• First Posted: Aug 14, 2017
• Last Update Posted: Oct 19, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daiichi Sankyo, Inc.: HER-2 positive breast cancer; Metastatic or Unresectable; Resistant or refractory to T-DM1; DESTINY - Breast 01; Trastuzumab deruxtecan; T-DXd
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants who met all of the inclusion and none of the exclusion criteria were enrolled and randomized to treatment (Part 1) or received DS-8201a at the recommended dose (Part 2).
Pre-assignment Detail	In Part 1, participants were randomized 1:1:1 to either 5.4 mg/kg, 6.4 mg/kg, or 7.4 mg/kg dose of DS-8201a. Two doses randomized 1:1 (6.4 mg/kg and 7.4 mg/kg) were further evaluated. In Part 2, all T-DM1 resistant refractory participants (cohort 2a) or T-DM1 intolerant (cohort 2b) received DS-8201a at the recommended dose.

Arm/Group Title	Part 1: DS-8201a Low Dose	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 2a: DS-8201a Low Dose	Part 2b (Exploratory): DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phase.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 2b in the continuation phase.
Period Title: Overall Study
STARTED	50	48	21	130	4
COMPLETED	0	0	0	0	0
NOT COMPLETED	50	48	21	130	4

Baseline Characteristics

Arm/Group Title	Part 1: DS-8201a Low Dose	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 2a: DS-8201a Low Dose	Part 2b (Exploratory): DS-8201a Low Dose	Total
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 2b in the continuation phase.	Total of all reporting groups
Overall Participants	50	48	21	130	4	253
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	35 70%	33 68.8%	16 76.2%	101 77.7%	4 100%	189 74.7%
>=65 years	15 30%	15 31.3%	5 23.8%	29 22.3%	0 0%	64 25.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.9 (11.3)	55.8 (13.0)	54.4 (10.5)	55.4 (11.9)	49.8 (9.2)	55.8 (11.8)
Sex: Female, Male (Count of Participants)
Female	50 100%	48 100%	21 100%	130 100%	4 100%	253 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2.1%	0 0%	0 0%	1 25%	2 0.8%
Asian	22 44%	22 45.8%	12 57.1%	47 36.2%	1 25%	104 41.1%
Native Hawaiian or Other Pacific Islander	1 2%	0 0%	0 0%	0 0%	0 0%	1 0.4%
Black or African American	2 4%	0 0%	1 4.8%	1 0.8%	1 25%	5 2%
White	24 48%	23 47.9%	8 38.1%	76 58.5%	1 25%	132 52.2%
More than one race	1 2%	1 2.1%	0 0%	2 1.5%	0 0%	4 1.6%
Unknown or Not Reported	0 0%	1 2.1%	0 0%	4 3.1%	0 0%	5 2%
Region of Enrollment (participants) [Number]
South Korea	7 14%	7 14.6%	0 0%	25 19.2%	1 25%	40 15.8%
Belgium	0 0%	2 4.2%	0 0%	7 5.4%	0 0%	9 3.6%
United States	15 30%	14 29.2%	10 47.6%	36 27.7%	2 50%	77 30.4%
Japan	16 32%	15 31.3%	11 52.4%	14 10.8%	0 0%	56 22.1%
Italy	0 0%	1 2.1%	0 0%	8 6.2%	1 25%	10 4%
United Kingdom	0 0%	0 0%	0 0%	12 9.2%	0 0%	12 4.7%
France	2 4%	1 2.1%	0 0%	17 13.1%	0 0%	20 7.9%
Spain	10 20%	8 16.7%	0 0%	11 8.5%	0 0%	29 11.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.
Time Frame	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)

Outcome Measure Data

Analysis Population Description

Objective response rate (ORR) was assessed in the Enrolled Analysis Set.at data cut-off date of 21 March 2019

Arm/Group Title	Part 1 and Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose
Arm/Group Description	All T-DM1 resistant/refractory (R/R) participants who were treated in Part 1 or Part 2a at the recommended (5.4 mg/kg) dose.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.
Measure Participants	180	184
Count of Participants [Participants]	109 218%	111 231.3%

2. Secondary Outcome

Title	Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.
Time Frame	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)

Outcome Measure Data

Analysis Population Description

Objective response rate (ORR) was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Arm/Group Title	Part 1 and Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose
Arm/Group Description	All T-DM1 resistant/refractory (R/R) participants who were treated in Part 1 or Part 2a at the recommended (5.4 mg/kg) dose.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.
Measure Participants	180	184	48	21
Count of Participants [Participants]	116 232%	118 245.8%	37 176.2%	18 13.8%

3. Secondary Outcome

Title	Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.
Time Frame	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)

Outcome Measure Data

Analysis Population Description

Best overall tumor response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Arm/Group Title	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 1 + Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.
Measure Participants	48	21	180	184
Complete response	3 6%	0 0%	4 19%	6 4.6%
Partial response	34 68%	18 37.5%	112 533.3%	112 86.2%
Stable disease	10 20%	3 6.3%	59 281%	61 46.9%
Progressive disease	0 0%	0 0%	4 19%	4 3.1%
Non-evaluable	1 2%	0 0%	1 4.8%	1 0.8%

4. Secondary Outcome

Title	Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.
Time Frame	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)

Outcome Measure Data

Analysis Population Description

Disease control rate (DCR) and clinical benefit rate (CBR) were assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Arm/Group Title	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 1 + Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.
Measure Participants	48	21	180	184
Disease control rate	47 94%	21 43.8%	175 833.3%	179 137.7%
Clinical benefit rate	41 82%	20 41.7%	127 604.8%	130 100%

5. Secondary Outcome

Title	Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.
Time Frame	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)

Outcome Measure Data

Analysis Population Description

Participants with CR or PR were analyzed. Estimated duration of response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Arm/Group Title	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 1 + Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.
Measure Participants	33	17	109	111
Median (95% Confidence Interval) [months]	NA	6.0	NA	NA

6. Secondary Outcome

Title	Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.
Time Frame	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)

Outcome Measure Data

Analysis Population Description

Progression-free survival was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Arm/Group Title	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 1 + Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.
Measure Participants	48	21	180	184
Median (95% Confidence Interval) [months]	NA	9.5	NA	NA

7. Secondary Outcome

Title	Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Description	Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.
Time Frame	Baseline up to Week 6, 12, 18, 24, 30, 36 post dose

Outcome Measure Data

Analysis Population Description

Best percent change from baseline in sum of diameters was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.

Arm/Group Title	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 1 + Part 2a: DS-8201a Low Dose	Part 1 + Part 2a + Part 2b: DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 1 or Part 2a.	All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 1 or Part 2a or Part 2b.
Measure Participants	48	21	180	184
Baseline to Week 6	-26.2 (18.3)	-32.9 (25.4)	-26.9 (21.6)	-26.9 (22.5)
Baseline to Week 12	-39.6 (22.7)	-43.6 (28.1)	-39.9 (24.5)	-40.1 (24.9)
Baseline to Week 18	-50.1 (22.1)	-58.5 (29.4)	-44.4 (27.8)	-44.9 (28.0)
Baseline to Week 24	-56.3 (22.1)	-61.9 (32.0)	-49.2 (30.6)	-49.3 (30.5)
Baseline to Week 30	-59.1 (26.1)	-63.9 (32.2)	-51.2 (29.2)	-51.5 (29.2)
Baseline to Week 36	-61.0 (26.7)	-54.6 (32.2)	-55.5 (29.9)	-55.5 (29.9)
Best percent change from baseline	-59.5 (28.2)	-65.3 (27.7)	-50.5 (28.3)	-50.6 (28.8)

8. Secondary Outcome

Title	Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)
Description	TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.
Time Frame	Day 0 to Day 47 post last dose

Outcome Measure Data

Analysis Population Description

Adverse event data were assessed in the Safety Analysis Set t data cut-off date of 21 March 2019.

Arm/Group Title	Part 1: DS-8201a Low Dose	Part 1: DS-8201a Medium Dose	Part 1: DS-8201a High Dose	Part 2a: DS-8201a Low Dose	Part 2b (Exploratory): DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.	All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in the continuation phase.	All participants who were T-DM1 intolerant and treated at the recommend dose (5.4 mg/kg) in the continuation phase.
Measure Participants	50	48	21	130	4
Any TEAE	50 100%	48 100%	21 100%	129 99.2%	4 100%
Drug-related TEAEs	50 100%	47 97.9%	21 100%	128 98.5%	4 100%
Drug-related TEAEs of CTCAE ≥Grade 3	26 52%	32 66.7%	16 76.2%	48 36.9%	3 75%
Any serious TEAE	11 22%	6 12.5%	8 38.1%	25 19.2%	0 0%
Drug-related serious TEAEs	6 12%	4 8.3%	5 23.8%	10 7.7%	0 0%
TEAEs associated with drug discontinuation	6 12%	6 12.5%	8 38.1%	8 6.2%	1 25%
Related TEAEs associated with drug discontinuation	6 12%	6 12.5%	8 38.1%	7 5.4%	1 25%
TEAEs associated with dose reduction	13 26%	19 39.6%	11 52.4%	21 16.2%	3 75%
Drug-related TEAEs associated with dose reduction	11 22%	18 37.5%	11 52.4%	20 15.4%	3 75%
TEAEs associated with dose interruption	19 38%	16 33.3%	12 57.1%	36 27.7%	2 50%
Related TEAEs associated with drug interruption	17 34%	13 27.1%	11 52.4%	29 22.3%	2 50%
TEAEs associated with death	1 2%	1 2.1%	2 9.5%	8 6.2%	0 0%
Drug-related TEAEs associated with death	0 0%	0 0%	1 4.8%	2 1.5%	0 0%

Adverse Events

Time Frame	Adverse event (AE) data were collected from Day 0 through Day 47 post last dose of study drug.
Adverse Event Reporting Description	A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
Arm/Group Title	Part 1: DS-8201a Low Dose		Part 1: DS-8201a Medium Dose		Part 1: DS-8201a High Dose		Part 2a: DS-8201a Low Dose		Part 2b (Exploratory): DS-8201a Low Dose
Arm/Group Description	T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.		T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.		T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases.		All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase.		All participants who were T-DM1 intolerant and treated at the recommend dose (5.4 mg/kg) in Part 2b in the continuation phase.
All Cause Mortality
	Part 1: DS-8201a Low Dose		Part 1: DS-8201a Medium Dose		Part 1: DS-8201a High Dose		Part 2a: DS-8201a Low Dose		Part 2b (Exploratory): DS-8201a Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/50 (12%)		7/48 (14.6%)		8/21 (38.1%)		13/130 (10%)		0/4 (0%)
Serious Adverse Events
	Part 1: DS-8201a Low Dose		Part 1: DS-8201a Medium Dose		Part 1: DS-8201a High Dose		Part 2a: DS-8201a Low Dose		Part 2b (Exploratory): DS-8201a Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/50 (22%)		6/48 (12.5%)		8/21 (38.1%)		25/130 (19.2%)		0/4 (0%)
Blood and lymphatic system disorders
Anemia	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Thrombocytopenia	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Hematuria	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Shock hemorrhagic	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Febrile neutropenia	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Cardiac disorders
Cardiac failure congestive	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Gastrointestinal disorders
Vomiting	2/50 (4%)		1/48 (2.1%)		0/21 (0%)		2/130 (1.5%)		0/4 (0%)
Intestinal obstruction	0/50 (0%)		0/48 (0%)		0/21 (0%)		3/130 (2.3%)		0/4 (0%)
Nausea	0/50 (0%)		2/48 (4.2%)		0/21 (0%)		3/130 (2.3%)		0/4 (0%)
Abdominal pain	0/50 (0%)		0/48 (0%)		0/21 (0%)		2/130 (1.5%)		0/4 (0%)
Abdominal abscess	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Ascites	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Dysphagia	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Upper gastrointestinal hemorrhage	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
General disorders
Disease progression	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		1/130 (0.8%)		0/4 (0%)
Pain	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
General physical health deterioration	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Asthenia	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Hepatobiliary disorders
Pyelonephritis	1/50 (2%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Acute hepatic failure	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Acute kidney injury	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Cholecystitis	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Immune system disorders
Hypersensitivity	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Infections and infestations
Cellulitis	3/50 (6%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Pneumonia	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		3/130 (2.3%)		0/4 (0%)
Urinary tract infection	0/50 (0%)		0/48 (0%)		0/21 (0%)		2/130 (1.5%)		0/4 (0%)
Diverticulitis	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Influenza	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Lung infection	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Parotitis	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Soft tissue infection	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Lower respiratory tract infection	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Lymphangitis	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Osteomyelitis	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Pneumonitis	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		1/130 (0.8%)		0/4 (0%)
Sepsis	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Injury, poisoning and procedural complications
Ilium fracture	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Femoral neck fracture	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Investigations
Neutrophil count decreased	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Alanine aminotransferase increased	0/50 (0%)		0/48 (0%)		2/21 (9.5%)		0/130 (0%)		0/4 (0%)
Aspartate aminotransferase increased	0/50 (0%)		0/48 (0%)		2/21 (9.5%)		0/130 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Hypokalemia	0/50 (0%)		0/48 (0%)		0/21 (0%)		2/130 (1.5%)		0/4 (0%)
Hyperkalemia	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Hyponatremia	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Muscular weakness	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Flank pain	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Nervous system disorders
Epilepsy	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Presyncope	1/50 (2%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Reproductive system and breast disorders
Genital hemorrhage	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/50 (4%)		0/48 (0%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Acute respiratory failure	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Dyspnea	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		1/130 (0.8%)		0/4 (0%)
Interstitial lung disease	0/50 (0%)		1/48 (2.1%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Pulmonary embolism	0/50 (0%)		1/48 (2.1%)		1/21 (4.8%)		0/130 (0%)		0/4 (0%)
Hypoxia	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Respiratory failure	0/50 (0%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Vascular disorders
Hypotension	0/50 (0%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: DS-8201a Low Dose		Part 1: DS-8201a Medium Dose		Part 1: DS-8201a High Dose		Part 2a: DS-8201a Low Dose		Part 2b (Exploratory): DS-8201a Low Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/50 (100%)		48/48 (100%)		21/21 (100%)		129/130 (99.2%)		4/4 (100%)
Blood and lymphatic system disorders
Anemia	16/50 (32%)		20/48 (41.7%)		10/21 (47.6%)		31/130 (23.8%)		0/4 (0%)
Neutropenia	7/50 (14%)		6/48 (12.5%)		5/21 (23.8%)		13/130 (10%)		1/4 (25%)
Lymphopenia	2/50 (4%)		0/48 (0%)		0/21 (0%)		8/130 (6.2%)		0/4 (0%)
Thrombocytopenia	2/50 (4%)		4/48 (8.3%)		2/21 (9.5%)		5/130 (3.8%)		1/4 (25%)
Leukopenia	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		3/130 (2.3%)		1/4 (25%)
Cardiac disorders
Mitral valve incompetence	0/50 (0%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		1/4 (25%)
Ear and labyrinth disorders
Tinnitus	0/50 (0%)		0/48 (0%)		0/21 (0%)		3/130 (2.3%)		1/4 (25%)
Eye disorders
Dry eye	4/50 (8%)		5/48 (10.4%)		3/21 (14.3%)		16/130 (12.3%)		0/4 (0%)
Keratitis	2/50 (4%)		3/48 (6.3%)		1/21 (4.8%)		1/130 (0.8%)		0/4 (0%)
Lacrimation increased	0/50 (0%)		3/48 (6.3%)		0/21 (0%)		3/130 (2.3%)		0/4 (0%)
Visual impairment	1/50 (2%)		2/48 (4.2%)		0/21 (0%)		1/130 (0.8%)		1/4 (25%)
Gastrointestinal disorders
Nausea	38/50 (76%)		40/48 (83.3%)		13/21 (61.9%)		101/130 (77.7%)		2/4 (50%)
Vomiting	23/50 (46%)		19/48 (39.6%)		7/21 (33.3%)		58/130 (44.6%)		2/4 (50%)
Constipation	16/50 (32%)		17/48 (35.4%)		10/21 (47.6%)		46/130 (35.4%)		1/4 (25%)
Diarrhea	15/50 (30%)		13/48 (27.1%)		4/21 (19%)		33/130 (25.4%)		1/4 (25%)
Stomatitis	10/50 (20%)		13/48 (27.1%)		4/21 (19%)		11/130 (8.5%)		2/4 (50%)
Dyspepsia	3/50 (6%)		5/48 (10.4%)		0/21 (0%)		19/130 (14.6%)		0/4 (0%)
Abdominal pain	5/50 (10%)		2/48 (4.2%)		3/21 (14.3%)		16/130 (12.3%)		0/4 (0%)
Gastroesophageal reflux disease	8/50 (16%)		2/48 (4.2%)		2/21 (9.5%)		7/130 (5.4%)		0/4 (0%)
Abdominal pain upper	3/50 (6%)		0/48 (0%)		0/21 (0%)		8/130 (6.2%)		0/4 (0%)
Hemorrhoids	3/50 (6%)		2/48 (4.2%)		1/21 (4.8%)		5/130 (3.8%)		1/4 (25%)
Abdominal distension	3/50 (6%)		1/48 (2.1%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Dysphagia	0/50 (0%)		0/48 (0%)		2/21 (9.5%)		4/130 (3.1%)		0/4 (0%)
Ascites	0/50 (0%)		3/48 (6.3%)		1/21 (4.8%)		3/130 (2.3%)		0/4 (0%)
Toothache	3/50 (6%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Abdominal discomfort	1/50 (2%)		0/48 (0%)		2/21 (9.5%)		0/130 (0%)		0/4 (0%)
General disorders
Fatigue	21/50 (42%)		24/48 (50%)		11/21 (52.4%)		65/130 (50%)		2/4 (50%)
Asthenia	9/50 (18%)		7/48 (14.6%)		0/21 (0%)		15/130 (11.5%)		1/4 (25%)
Pyrexia	2/50 (4%)		10/48 (20.8%)		4/21 (19%)		11/130 (8.5%)		0/4 (0%)
Mucosal inflammation	1/50 (2%)		2/48 (4.2%)		0/21 (0%)		10/130 (7.7%)		0/4 (0%)
Odema peripheral	2/50 (4%)		6/48 (12.5%)		0/21 (0%)		8/130 (6.2%)		0/4 (0%)
Malaise	3/50 (6%)		3/48 (6.3%)		5/21 (23.8%)		2/130 (1.5%)		0/4 (0%)
Infections and infestations
Urinary tract infection	4/50 (8%)		3/48 (6.3%)		2/21 (9.5%)		12/130 (9.2%)		1/4 (25%)
Upper respiratory tract infection	6/50 (12%)		1/48 (2.1%)		1/21 (4.8%)		10/130 (7.7%)		0/4 (0%)
Nasopharyngitis	5/50 (10%)		3/48 (6.3%)		3/21 (14.3%)		8/130 (6.2%)		0/4 (0%)
Cystitis	2/50 (4%)		2/48 (4.2%)		1/21 (4.8%)		2/130 (1.5%)		1/4 (25%)
Cellulitis	3/50 (6%)		1/48 (2.1%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Herpes zoster	3/50 (6%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Influenza	0/50 (0%)		2/48 (4.2%)		2/21 (9.5%)		3/130 (2.3%)		0/4 (0%)
Conjunctivitis	0/50 (0%)		3/48 (6.3%)		1/21 (4.8%)		2/130 (1.5%)		0/4 (0%)
Pharyngitis	1/50 (2%)		3/48 (6.3%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Infusion-related reaction	3/50 (6%)		0/48 (0%)		0/21 (0%)		1/130 (0.8%)		0/4 (0%)
Investigations
Neutrophil count decreased	16/50 (32%)		17/48 (35.4%)		12/21 (57.1%)		21/130 (16.2%)		0/4 (0%)
White blood cell count decreased	12/50 (24%)		15/48 (31.3%)		13/21 (61.9%)		20/130 (15.4%)		0/4 (0%)
Platelet count decreased	8/50 (16%)		11/48 (22.9%)		7/21 (33.3%)		16/130 (12.3%)		0/4 (0%)
Aspartate aminotransferase increased	9/50 (18%)		5/48 (10.4%)		7/21 (33.3%)		14/130 (10.8%)		0/4 (0%)
Alanine aminotransferase increased	7/50 (14%)		4/48 (8.3%)		7/21 (33.3%)		10/130 (7.7%)		0/4 (0%)
Lymphocyte count decreased	3/50 (6%)		5/48 (10.4%)		2/21 (9.5%)		11/130 (8.5%)		0/4 (0%)
Weight decreased	5/50 (10%)		6/48 (12.5%)		4/21 (19%)		6/130 (4.6%)		1/4 (25%)
Blood bilirubin increased	4/50 (8%)		3/48 (6.3%)		5/21 (23.8%)		7/130 (5.4%)		0/4 (0%)
Blood alkaline phosphatase increased	1/50 (2%)		4/48 (8.3%)		6/21 (28.6%)		7/130 (5.4%)		0/4 (0%)
Electrocardiogram QT prolonged	5/50 (10%)		0/48 (0%)		1/21 (4.8%)		3/130 (2.3%)		0/4 (0%)
Blood lactate dehydrogenase increased	4/50 (8%)		0/48 (0%)		3/21 (14.3%)		1/130 (0.8%)		0/4 (0%)
Gamma-glutamyltransferase increased	1/50 (2%)		6/48 (12.5%)		1/21 (4.8%)		4/130 (3.1%)		0/4 (0%)
Troponin I increased	3/50 (6%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		0/4 (0%)
Ejection fraction decreased	1/50 (2%)		1/48 (2.1%)		0/21 (0%)		0/130 (0%)		1/4 (25%)
Metabolism and nutrition disorders
Decreased appetite	15/50 (30%)		21/48 (43.8%)		6/21 (28.6%)		37/130 (28.5%)		1/4 (25%)
Hypokalemia	3/50 (6%)		3/48 (6.3%)		4/21 (19%)		16/130 (12.3%)		0/4 (0%)
Hypoalbuminemia	1/50 (2%)		3/48 (6.3%)		4/21 (19%)		5/130 (3.8%)		0/4 (0%)
Hypomagnesemia	2/50 (4%)		0/48 (0%)		3/21 (14.3%)		4/130 (3.1%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/50 (2%)		2/48 (4.2%)		3/21 (14.3%)		14/130 (10.8%)		0/4 (0%)
Arthralgia	3/50 (6%)		3/48 (6.3%)		1/21 (4.8%)		8/130 (6.2%)		0/4 (0%)
Myalgia	4/50 (8%)		3/48 (6.3%)		0/21 (0%)		7/130 (5.4%)		0/4 (0%)
Muscle spasms	1/50 (2%)		1/48 (2.1%)		1/21 (4.8%)		8/130 (6.2%)		0/4 (0%)
Pain in extremity	2/50 (4%)		4/48 (8.3%)		2/21 (9.5%)		3/130 (2.3%)		0/4 (0%)
Neck pain	0/50 (0%)		1/48 (2.1%)		2/21 (9.5%)		1/130 (0.8%)		0/4 (0%)
Nervous system disorders
Headache	7/50 (14%)		10/48 (20.8%)		2/21 (9.5%)		26/130 (20%)		1/4 (25%)
Dysgeusia	4/50 (8%)		5/48 (10.4%)		1/21 (4.8%)		8/130 (6.2%)		1/4 (25%)
Peripheral sensory neuropathy	3/50 (6%)		4/48 (8.3%)		2/21 (9.5%)		9/130 (6.9%)		0/4 (0%)
Neuropathy peripheral	2/50 (4%)		1/48 (2.1%)		2/21 (9.5%)		7/130 (5.4%)		1/4 (25%)
Cognitive disorder	0/50 (0%)		0/48 (0%)		0/21 (0%)		0/130 (0%)		1/4 (25%)
Psychiatric disorders
Insomnia	5/50 (10%)		5/48 (10.4%)		5/21 (23.8%)		6/130 (4.6%)		0/4 (0%)
Anxiety	3/50 (6%)		2/48 (4.2%)		2/21 (9.5%)		7/130 (5.4%)		0/4 (0%)
Dizziness	6/50 (12%)		4/48 (8.3%)		1/21 (4.8%)		9/130 (6.9%)		1/4 (25%)
Renal and urinary disorders
Hematuria	0/50 (0%)		1/48 (2.1%)		1/21 (4.8%)		1/130 (0.8%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Cough	9/50 (18%)		7/48 (14.6%)		4/21 (19%)		23/130 (17.7%)		0/4 (0%)
Dyspnea	5/50 (10%)		0/48 (0%)		2/21 (9.5%)		19/130 (14.6%)		0/4 (0%)
Epistaxis	6/50 (12%)		3/48 (6.3%)		1/21 (4.8%)		16/130 (12.3%)		0/4 (0%)
Pneumonitis	4/50 (8%)		1/48 (2.1%)		2/21 (9.5%)		5/130 (3.8%)		0/4 (0%)
Interstitial lung disease	4/50 (8%)		3/48 (6.3%)		5/21 (23.8%)		1/130 (0.8%)		0/4 (0%)
Hypoxia	0/50 (0%)		0/48 (0%)		1/21 (4.8%)		2/130 (1.5%)		1/4 (25%)
Skin and subcutaneous tissue disorders
Alopecia	25/50 (50%)		28/48 (58.3%)		8/21 (38.1%)		61/130 (46.9%)		2/4 (50%)
Rash	1/50 (2%)		6/48 (12.5%)		1/21 (4.8%)		10/130 (7.7%)		0/4 (0%)
Dry skin	2/50 (4%)		1/48 (2.1%)		1/21 (4.8%)		7/130 (5.4%)		0/4 (0%)
Nail disorder	1/50 (2%)		0/48 (0%)		0/21 (0%)		7/130 (5.4%)		0/4 (0%)
Skin hyperpigmentation	3/50 (6%)		0/48 (0%)		2/21 (9.5%)		4/130 (3.1%)		0/4 (0%)
Pruritus	0/50 (0%)		3/48 (6.3%)		0/21 (0%)		4/130 (3.1%)		0/4 (0%)
Vascular disorders
Hypertension	0/50 (0%)		0/48 (0%)		0/21 (0%)		4/130 (3.1%)		1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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