DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01)
Sponsor
Daiichi Sankyo Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT03384940
Collaborator
Daiichi Sankyo, Inc. (Industry), AstraZeneca (Industry)
86
25
3
32.6
3.4
0.1
Study Details
Study Description
Brief Summary
The main objective of this study is to test the safety and effectiveness of DS-8201a for participants with HER2-expressing advanced colorectal cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
At study start, only Cohort A is active.
If, and when, Cohort B and C become active depends on the assessment of benefit and risk observed in the program.
The sponsor will inform the investigators if, and when, Cohort B and C are active.
Study Design
Study Type:
Interventional
Actual Enrollment
:
86 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Colorectal Cancer
Actual Study Start Date
:
Feb 23, 2018
Actual Primary Completion Date
:
Aug 9, 2019
Actual Study Completion Date
:
Nov 10, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DS-8201a Cohort A Cohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks |
Drug: DS-8201a
DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration
Other Names:
|
| Experimental: DS-8201a Cohort B Cohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks |
Drug: DS-8201a
DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration
Other Names:
|
| Experimental: DS-8201a Cohort C Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks |
Drug: DS-8201a
DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Best Objective Response Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose]
Best objective response was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (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 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.
- Number of Participants With Objective Response Rate Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose]
Objective response rate (defined as CR+PR) was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (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.
Secondary Outcome Measures
- Number of Participants With Best Objective Response Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose]
Best objective response was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (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 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.
- Number of Participants With Objective Response Rate Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose]
Objective response rate (defined as CR+PR) was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (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.
- Duration of Response (Confirmed and Unconfirmed) Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Date of first documentation of objective response (CR or PR) up to date of first documentation of PD, up to approximately 18 months post-dose]
Duration of response (DoR) is defined as the time from the date of the first documentation of an objective response (CR[disappearance of all target lesions] or PR [at least a 30% decrease in the sum of diameters of target lesions]) to the date of the first documentation of PD (at least a 20% increase in the sum of diameters of target lesions). Duration of response was measured for responding participants (CR or PR) only. Month was calculated as (duration of response days × 12)/365.25 for duration of response and calculated as (time to response days × 12)/365.25 for time to response.
- Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose]
Disease control rate (DCR) was defined as the proportion of participants who achieved a best overall response of CR + PR + SD based on independent central review and investigator assessment. 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).
- Progression-Free Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months]
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
- Progression-Free Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months]
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.Point estimates at 3, 6, 9, and 12 months are based on Kaplan-Meier estimate. CI is computed using the Brookmeyer-Crowley method. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.
- Overall Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Time from the date of first dose to date of death from any cause, up to approximately 18 months]
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
- Overall Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [Time from the date of first dose to date of death from any cause, up to approximately 18 months]
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.
- Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI]
Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
- Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI]
Maximum serum concentration (Cmax) of MAAA-1181a was assessed.
- Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI]
Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.
- Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI]
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of DS-8201a and total anti-HER2 antibody were assessed.
- Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) of MAAA-1181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI]
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.
- Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months]
A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Has pathologically documented unresectable, recurrent, or metastatic colorectal adenocarcinoma (until sponsor's notification to the study sites, subject must be a RAS/BRAF wild-type cancer)
-
Has received at least 2 prior regimens of standard treatment
-
Has measurable disease assessed by the investigator based on RECIST version 1.1.
-
Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
Exclusion Criteria:
-
Has a medical history of myocardial infarction within 6 months, symptomatic congestive heart failure
-
Has a medical history of clinically significant lung disease
-
Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Medical Center | Duarte | California | United States | 91010 |
| 2 | University of Southern California | Los Angeles | California | United States | 90089 |
| 3 | UCLA Health | Santa Monica | California | United States | 90404 |
| 4 | Mayo Clinic Jacksonville | Jacksonville | Florida | United States | 32224-1865 |
| 5 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 6 | Greenville Health System Cancer Institute | Greenville | South Carolina | United States | 29605-4255 |
| 7 | West Cancer Center | Germantown | Tennessee | United States | 38138 |
| 8 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 9 | MD Anderson Cancer Center, University of Texas | Houston | Texas | United States | 77030-4000 |
| 10 | Università degli studi della Campania L.Vanvitelli | Napoli | Campania | Italy | 80131 |
| 11 | Oncology Institute Veneto IOV-IRCCS | Padova | Ferrara | Italy | 35128 |
| 12 | ASST Grande Ospedale Metropolitano Niguarda | Milano | Lombardo | Italy | 20162 |
| 13 | Fondazione IRCCS - Istituto Nazionale dei Tumori | Milan | Italy | 20133 | |
| 14 | Aichi Cancer Center Hospital | Nagoya | Aichi | Japan | 464-8681 |
| 15 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
| 16 | National Hospital Organization Shikoku Cancer Center | Matsuyama | Ehime | Japan | 791-0280 |
| 17 | Hokkaido University Hospital | Sapporo | Hokkaido | Japan | 060-8648 |
| 18 | Kindai University Hospital | Ōsaka-sayama | Osaka | Japan | 589-8511 |
| 19 | The Cancer Institute Hospital of Japanese Foundation for Cancer Research | Koto-Ku | Tokyo | Japan | 135-8550 |
| 20 | National Hospital Organization Kyushu Cancer Center | Fukuoka | Japan | 811-1395 | |
| 21 | Clinica Universidad de Navarra | Pamplona | Navarre | Spain | 31008 |
| 22 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 08035 | |
| 23 | Hospital Universitari Clinic de Barcelona | Barcelona | Spain | 08036 | |
| 24 | Royal Marsden Institute (Chelsea) | Chelsea | London, England | United Kingdom | SM2 5PT |
| 25 | Royal Marsden Institute (Sutton) | Sutton | Surrey, England | United Kingdom | SW3 6JJ |
Sponsors and Collaborators
- Daiichi Sankyo Co., Ltd.
- Daiichi Sankyo, Inc.
- AstraZeneca
Investigators
- Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT03384940
Other Study ID Numbers:
- DS8201-A-J203
- 2017-003466-28
- 173808
- DESTINY-C01
First Posted:
Dec 28, 2017
Last Update Posted:
Oct 18, 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 Co., Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 86 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at clinic centers in Japan, United States, Spain, and Italy. |
|---|---|
| Pre-assignment Detail | After tissue screening, a total of 86 participants were eligible based on confirmation of HER2 status. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Period Title: Overall Study | |||
| STARTED | 53 | 15 | 18 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 53 | 15 | 18 |
Baseline Characteristics
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. | Total of all reporting groups |
| Overall Participants | 53 | 15 | 18 | 86 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
35
66%
|
8
53.3%
|
13
72.2%
|
56
65.1%
|
| >=65 years |
18
34%
|
7
46.7%
|
5
27.8%
|
30
34.9%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
57.5
(11.72)
|
61.5
(11.95)
|
58.5
(9.97)
|
58.4
(11.38)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
28
52.8%
|
5
33.3%
|
7
38.9%
|
40
46.5%
|
| Male |
25
47.2%
|
10
66.7%
|
11
61.1%
|
46
53.5%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
16
30.2%
|
3
20%
|
8
44.4%
|
27
31.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
34
64.2%
|
11
73.3%
|
8
44.4%
|
53
61.6%
|
| More than one race |
1
1.9%
|
0
0%
|
1
5.6%
|
2
2.3%
|
| Unknown or Not Reported |
2
3.8%
|
1
6.7%
|
1
5.6%
|
4
4.7%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
10
18.9%
|
3
20%
|
1
5.6%
|
14
16.3%
|
| Japan |
15
28.3%
|
3
20%
|
8
44.4%
|
26
30.2%
|
| Italy |
26
49.1%
|
7
46.7%
|
8
44.4%
|
41
47.7%
|
| Spain |
2
3.8%
|
1
6.7%
|
1
5.6%
|
4
4.7%
|
| United Kingdom |
0
0%
|
1
6.7%
|
0
0%
|
1
1.2%
|
Outcome Measures
| Title | Number of Participants With Best Objective Response Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Best objective response was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (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 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 up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Confirmed CR |
0
0%
|
0
0%
|
0
0%
|
| Confirmed PR |
24
45.3%
|
0
0%
|
0
0%
|
| Confirmed SD |
20
37.7%
|
9
60%
|
4
22.2%
|
| Confirmed PD |
5
9.4%
|
5
33.3%
|
10
55.6%
|
| Confirmed Non-evaluable |
4
7.5%
|
1
6.7%
|
4
22.2%
|
| Unconfirmed CR |
0
0%
|
0
0%
|
0
0%
|
| Unconfirmed PR |
26
49.1%
|
0
0%
|
0
0%
|
| Unconfirmed SD |
18
34%
|
9
60%
|
4
22.2%
|
| Unconfirmed PD |
5
9.4%
|
5
33.3%
|
10
55.6%
|
| Unconfirmed Non-evaluable |
4
7.5%
|
1
6.7%
|
4
22.2%
|
| Title | Number of Participants With Objective Response Rate Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Objective response rate (defined as CR+PR) was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (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. |
| Time Frame | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Confirmed CR+PR |
24
45.3%
|
0
0%
|
0
0%
|
| Confirmed CR+PR (within 3 months) |
10
18.9%
|
0
0%
|
0
0%
|
| Confirmed CR+PR (within 6 months) |
23
43.4%
|
0
0%
|
0
0%
|
| Confirmed CR+PR (within 9 months) |
24
45.3%
|
0
0%
|
0
0%
|
| Confirmed CR+PR (12 months) |
24
45.3%
|
0
0%
|
0
0%
|
| Unconfirmed CR+PR |
26
49.1%
|
0
0%
|
0
0%
|
| Unconfirmed CR+PR (within 3 months) |
20
37.7%
|
0
0%
|
0
0%
|
| Unconfirmed CR+PR (within 6 months) |
25
47.2%
|
0
0%
|
0
0%
|
| Unconfirmed CR+PR (within 9 months) |
25
47.2%
|
0
0%
|
0
0%
|
| Unconfirmed CR+PR (within 12 months) |
25
47.2%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Best Objective Response Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Best objective response was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (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 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 up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Confirmed CR |
0
0%
|
0
0%
|
0
0%
|
| Confirmed PR |
25
47.2%
|
0
0%
|
0
0%
|
| Confirmed SD |
18
34%
|
7
46.7%
|
6
33.3%
|
| Confirmed PD |
6
11.3%
|
7
46.7%
|
8
44.4%
|
| Confirmed Non-evaluable |
4
7.5%
|
1
6.7%
|
4
22.2%
|
| Unconfirmed CR |
0
0%
|
0
0%
|
0
0%
|
| Unconfirmed PR |
28
52.8%
|
0
0%
|
0
0%
|
| Unconfirmed SD |
15
28.3%
|
7
46.7%
|
6
33.3%
|
| Unconfirmed PD |
6
11.3%
|
7
46.7%
|
8
44.4%
|
| Unconfirmed Non-evaluable |
4
7.5%
|
1
6.7%
|
4
22.2%
|
| Title | Number of Participants With Objective Response Rate Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Objective response rate (defined as CR+PR) was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (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. |
| Time Frame | Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Confirmed CR+PR |
25
47.2%
|
0
0%
|
0
0%
|
| Unconfirmed CR+PR |
28
52.8%
|
0
0%
|
0
0%
|
| Title | Duration of Response (Confirmed and Unconfirmed) Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Duration of response (DoR) is defined as the time from the date of the first documentation of an objective response (CR[disappearance of all target lesions] or PR [at least a 30% decrease in the sum of diameters of target lesions]) to the date of the first documentation of PD (at least a 20% increase in the sum of diameters of target lesions). Duration of response was measured for responding participants (CR or PR) only. Month was calculated as (duration of response days × 12)/365.25 for duration of response and calculated as (time to response days × 12)/365.25 for time to response. |
| Time Frame | Date of first documentation of objective response (CR or PR) up to date of first documentation of PD, up to approximately 18 months post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of response was assessed only in Cohort A in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A |
|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 |
| Confirmed DoR |
7.0
|
| Unconfirmed DoR |
7.0
|
| Title | Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Disease control rate (DCR) was defined as the proportion of participants who achieved a best overall response of CR + PR + SD based on independent central review and investigator assessment. 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 up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of response was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Confirmed CR+PR+SD (Independent Central Review) |
44
83%
|
9
60%
|
4
22.2%
|
| Unconfirmed CR+PR+SD (Independent Central Review) |
44
83%
|
9
60%
|
4
22.2%
|
| Confirmed CR+PR+SD (Investigator) |
43
81.1%
|
7
46.7%
|
6
33.3%
|
| Unconfirmed CR+PR+SD (Investigator) |
43
81.1%
|
7
46.7%
|
6
33.3%
|
| Title | Progression-Free Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review 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 | Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Progression-free survival was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Median (95% Confidence Interval) [months] |
6.9
|
2.1
|
1.4
|
| Title | Progression-Free Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.Point estimates at 3, 6, 9, and 12 months are based on Kaplan-Meier estimate. CI is computed using the Brookmeyer-Crowley method. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported. |
| Time Frame | Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Progression-free survival was assessed in the Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Progression-free survival at 3 months |
74.4
|
38.3
|
7.5
|
| Progression-free survival at 6 months |
55
|
0
|
0
|
| Progression-free survival at 9 months |
34.1
|
0
|
0
|
| Progression-free survival at 12 months |
19.0
|
0
|
0
|
| Title | Overall Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. |
| Time Frame | Time from the date of first dose to date of death from any cause, up to approximately 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall survival was assessed in Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Median (95% Confidence Interval) [months] |
15.5
|
7.3
|
7.7
|
| Title | Overall Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer |
|---|---|
| Description | Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported. |
| Time Frame | Time from the date of first dose to date of death from any cause, up to approximately 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall survival was assessed in Full Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Overall survival at 3 months |
86.8
|
86.7
|
77.0
|
| Overall survival at 6 months |
73.6
|
53.3
|
57.8
|
| Overall survival at 9 months |
62.0
|
38.1
|
43.3
|
| Overall survival at 12 months |
60.0
|
38.1
|
28.9
|
| Title | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer |
|---|---|
| Description | Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed. |
| Time Frame | Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed Pharmacokinetic Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| DS-8201a |
135
(32.7)
|
123
(29.5)
|
122
(41.5)
|
| Total anti-HER2 antibody |
130
(35.1)
|
106
(24.6)
|
109
(35.4)
|
| Title | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer |
|---|---|
| Description | Maximum serum concentration (Cmax) of MAAA-1181a was assessed. |
| Time Frame | Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed Pharmacokinetic Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Mean (Standard Deviation) [ng/mL] |
15.8
(7.67)
|
12.9
(6.40)
|
15.1
(5.30)
|
| Title | Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer |
|---|---|
| Description | Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed. |
| Time Frame | Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed Pharmacokinetic Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| DS-8201a |
1.95
|
1.72
|
3.00
|
| Total anti-HER2 antibody |
1.72
|
1.68
|
1.93
|
| MAAA-1181a |
5.17
|
5.00
|
5.25
|
| Title | Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer |
|---|---|
| Description | Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of DS-8201a and total anti-HER2 antibody were assessed. |
| Time Frame | Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed Pharmacokinetic Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| DS-8201a: AUC21d |
610
(198)
|
571
(208)
|
577
(219)
|
| DS-8201a: AUClast |
600
(204)
|
559
(211)
|
577
(237)
|
| Total anti-HER2 antibody: AUC21d |
661
(218)
|
569
(224)
|
574
(219)
|
| Total anti-HER2 antibody: AUClast |
638
(235)
|
558
(225)
|
555
(224)
|
| Title | Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) of MAAA-1181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer |
|---|---|
| Description | Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed. |
| Time Frame | Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic parameters were assessed Pharmacokinetic Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| MAAA-1181a: AUC21d |
60.2
(42.7)
|
45.0
(28.1)
|
55.1
(19.6)
|
| MAAA-1181a: AUClast |
59.5
(42.1)
|
47.1
(29.4)
|
62.5
(19.6)
|
| Title | Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer |
|---|---|
| Description | A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03. |
| Time Frame | From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Adverse events were assessed in the Safety Analysis Set. |
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. |
| Measure Participants | 53 | 15 | 18 |
| Any TEAE |
53
100%
|
15
100%
|
18
100%
|
| Nausea |
37
69.8%
|
9
60%
|
7
38.9%
|
| Anaemia |
21
39.6%
|
4
26.7%
|
6
33.3%
|
| Decreased appetite |
18
34%
|
5
33.3%
|
7
38.9%
|
| Fatigue |
21
39.6%
|
7
46.7%
|
3
16.7%
|
| Neutrophil count decreased |
20
37.7%
|
2
13.3%
|
4
22.2%
|
| Platelet count decreased |
17
32.1%
|
4
26.7%
|
7
38.9%
|
| Vomiting |
23
43.4%
|
3
20%
|
1
5.6%
|
| Diarrhoea |
19
35.8%
|
0
0%
|
4
22.2%
|
| Alopecia |
12
22.6%
|
4
26.7%
|
1
5.6%
|
| Constipation |
10
18.9%
|
3
20%
|
1
5.6%
|
| Hypokalaemia |
9
17%
|
1
6.7%
|
4
22.2%
|
| Aspartate aminotransferase increased |
6
11.3%
|
1
6.7%
|
4
22.2%
|
| Malaise |
5
9.4%
|
0
0%
|
4
22.2%
|
| Interstitial lung disease |
4
7.5%
|
3
20%
|
1
5.6%
|
| Dyspnoea |
3
5.7%
|
3
20%
|
0
0%
|
Adverse Events
| Time Frame | Adverse events were collected from the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or having worsened in severity or seriousness after initiation of the study drug until 40 (+7) days after the last dose of the study drug. | |||||
| Arm/Group Title | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | |||
| Arm/Group Description | Participants in Cohort A were HER2-positive (IHC 3+ or IHC 2+/ISH +) who received DS-8201a once every 3 weeks. | Participants in Cohort B were HER2 IHC 2+/ISH - who received DS-8201a once every 3 weeks. | Participants in Cohort C were HER2/IHC 1+ who received DS-8201a once every 3 weeks. | |||
All Cause Mortality |
||||||
| DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 36/53 (67.9%) | 10/15 (66.7%) | 12/18 (66.7%) | |||
Serious Adverse Events |
||||||
| DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/53 (37.7%) | 6/15 (40%) | 9/18 (50%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/53 (3.8%) | 0/15 (0%) | 0/18 (0%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 2/53 (3.8%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Nausea | 2/53 (3.8%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Gastritis | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Gastrointestinal ulcer | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Ileus | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Ileus paralytic | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Vomiting | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Intestinal obstruction | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Small intestinal obstruction | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| General disorders | ||||||
| Disease progression | 1/53 (1.9%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Pyrexia | 1/53 (1.9%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Fatigue | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| General physical health deterioration | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct stenosis | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Bile duct obstruction | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Cholecystitis | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Infections and infestations | ||||||
| Sepsis | 3/53 (5.7%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Urinary tract infection | 2/53 (3.8%) | 0/15 (0%) | 0/18 (0%) | |||
| Infected fistula | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Lung infection | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Pneumonia klebsiella | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Abdominal sepsis | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Pneumonia | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Gastrointestinal stoma complication | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Femoral neck fracture | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Investigations | ||||||
| Neutrophil count decreased | 2/53 (3.8%) | 0/15 (0%) | 0/18 (0%) | |||
| Platelet count decreased | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypokalaemia | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cancer pain | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Nervous system disorders | ||||||
| Meningism | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Seizure | 1/53 (1.9%) | 0/15 (0%) | 0/18 (0%) | |||
| Renal and urinary disorders | ||||||
| Hydronephrosis | 2/53 (3.8%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Acute kidney injury | 0/53 (0%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Interstitial lung disease | 1/53 (1.9%) | 2/15 (13.3%) | 1/18 (5.6%) | |||
| Pneumonitis | 2/53 (3.8%) | 0/15 (0%) | 0/18 (0%) | |||
| Dyspnoea | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/53 (100%) | 15/15 (100%) | 18/18 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 21/53 (39.6%) | 4/15 (26.7%) | 6/18 (33.3%) | |||
| Neutropenia | 5/53 (9.4%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Thrombocytopenia | 0/53 (0%) | 0/15 (0%) | 2/18 (11.1%) | |||
| Leukocytosis | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Eye disorders | ||||||
| Eye pain | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Keratitis | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Dry eye | 5/53 (9.4%) | 0/15 (0%) | 0/18 (0%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 37/53 (69.8%) | 9/15 (60%) | 7/18 (38.9%) | |||
| Vomiting | 23/53 (43.4%) | 3/15 (20%) | 1/18 (5.6%) | |||
| Diarrhoea | 19/53 (35.8%) | 0/15 (0%) | 4/18 (22.2%) | |||
| Constipation | 10/53 (18.9%) | 3/15 (20%) | 1/18 (5.6%) | |||
| Stomatitis | 6/53 (11.3%) | 2/15 (13.3%) | 1/18 (5.6%) | |||
| Abdominal pain | 8/53 (15.1%) | 2/15 (13.3%) | 0/18 (0%) | |||
| Abdominal pain upper | 3/53 (5.7%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Gastritis | 3/53 (5.7%) | 0/15 (0%) | 0/18 (0%) | |||
| Ascites | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Gastrointestinal stoma complication | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Haemorrhoids | 0/53 (0%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Ileus paralytic | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Intestinal prolapse | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Small intestinal obstruction | 1/53 (1.9%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Abdominal sepsis | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Intestinal obstruction | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| General disorders | ||||||
| Fatigue | 21/53 (39.6%) | 7/15 (46.7%) | 3/18 (16.7%) | |||
| Asthenia | 6/53 (11.3%) | 2/15 (13.3%) | 3/18 (16.7%) | |||
| Oedema peripheral | 8/53 (15.1%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Pyrexia | 8/53 (15.1%) | 1/15 (6.7%) | 3/18 (16.7%) | |||
| Malaise | 5/53 (9.4%) | 0/15 (0%) | 4/18 (22.2%) | |||
| Disease progression | 1/53 (1.9%) | 0/15 (0%) | 1/18 (5.6%) | |||
| General physical health deterioration | 0/53 (0%) | 0/15 (0%) | 2/18 (11.1%) | |||
| Generalised oedema | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Oedema | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Fluid retention | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Cholecystitis | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Infections and infestations | ||||||
| Sepsis | 3/53 (5.7%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Urinary tract infection | 5/53 (9.4%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Cystitis | 4/53 (7.5%) | 0/15 (0%) | 0/18 (0%) | |||
| Lung infection | 1/53 (1.9%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Fungal infection | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Oral herpes | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Influenza | 1/53 (1.9%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Oral candidiasis | 1/53 (1.9%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Pneumonia | 1/53 (1.9%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Pneumonia bacterial | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Investigations | ||||||
| Neutrophil count decreased | 20/53 (37.7%) | 2/15 (13.3%) | 4/18 (22.2%) | |||
| Platelet count decreased | 17/53 (32.1%) | 4/15 (26.7%) | 7/18 (38.9%) | |||
| White blood cell count decreased | 11/53 (20.8%) | 1/15 (6.7%) | 2/18 (11.1%) | |||
| Aspartate aminotransferase increased | 6/53 (11.3%) | 1/15 (6.7%) | 4/18 (22.2%) | |||
| Alanine aminotransferase increased | 5/53 (9.4%) | 1/15 (6.7%) | 3/18 (16.7%) | |||
| Blood creatinine increased | 5/53 (9.4%) | 0/15 (0%) | 2/18 (11.1%) | |||
| Weight decreased | 5/53 (9.4%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Blood alkaline phosphatase increased | 3/53 (5.7%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Blood bilirubin increased | 3/53 (5.7%) | 1/15 (6.7%) | 2/18 (11.1%) | |||
| Blood lactate dehydrogenase increased | 2/53 (3.8%) | 0/15 (0%) | 2/18 (11.1%) | |||
| Haemoglobin decreased | 3/53 (5.7%) | 0/15 (0%) | 0/18 (0%) | |||
| Lymphocyte count decreased | 2/53 (3.8%) | 2/15 (13.3%) | 0/18 (0%) | |||
| Blood calcium decreased | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Blood potassium decreased | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Blood magnesium decreased | 2/53 (3.8%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 18/53 (34%) | 5/15 (33.3%) | 7/18 (38.9%) | |||
| Hypokalaemia | 9/53 (17%) | 1/15 (6.7%) | 4/18 (22.2%) | |||
| Hypomagnesaemia | 4/53 (7.5%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Hypoalbuminaemia | 2/53 (3.8%) | 0/15 (0%) | 2/18 (11.1%) | |||
| Hypocalcaemia | 2/53 (3.8%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Cachexia | 0/53 (0%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Dehydration | 1/53 (1.9%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Hypercalcaemia | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Hyperuricaemia | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Hyponatraemia | 0/53 (0%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 5/53 (9.4%) | 0/15 (0%) | 0/18 (0%) | |||
| Arthralgia | 3/53 (5.7%) | 0/15 (0%) | 0/18 (0%) | |||
| Myalgia | 3/53 (5.7%) | 0/15 (0%) | 0/18 (0%) | |||
| Musculoskeletal pain | 2/53 (3.8%) | 2/15 (13.3%) | 0/18 (0%) | |||
| Proctalgia | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cancer pain | 1/53 (1.9%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Nervous system disorders | ||||||
| Dysgeusia | 4/53 (7.5%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Paraesthesia | 2/53 (3.8%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Headache | 2/53 (3.8%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Vasogenic cerebral oedema | 0/53 (0%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 3/53 (5.7%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Mood altered | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Renal and urinary disorders | ||||||
| Hydronephrosis | 2/53 (3.8%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Acute kidney injury | 2/53 (3.8%) | 1/15 (6.7%) | 1/18 (5.6%) | |||
| Pollakiuria | 1/53 (1.9%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Dysuria | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 8/53 (15.1%) | 2/15 (13.3%) | 0/18 (0%) | |||
| Dyspnoea | 3/53 (5.7%) | 3/15 (20%) | 0/18 (0%) | |||
| Interstitial lung disease | 4/53 (7.5%) | 3/15 (20%) | 1/18 (5.6%) | |||
| Productive cough | 3/53 (5.7%) | 0/15 (0%) | 0/18 (0%) | |||
| Upper respiratory tract infection | 2/53 (3.8%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 12/53 (22.6%) | 4/15 (26.7%) | 1/18 (5.6%) | |||
| Flushing | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Jaundice | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 3/53 (5.7%) | 0/15 (0%) | 1/18 (5.6%) | |||
| Hypotension | 0/53 (0%) | 0/15 (0%) | 2/18 (11.1%) | |||
| Retinal vein occlusion | 0/53 (0%) | 1/15 (6.7%) | 0/18 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Contact for Clinical Trial Information |
|---|---|
| Organization | Daiichi Sanyko, Inc. |
| Phone | 908-992-6400 |
| CTRinfo@dsi.com |
Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT03384940
Other Study ID Numbers:
- DS8201-A-J203
- 2017-003466-28
- 173808
- DESTINY-C01
First Posted:
Dec 28, 2017
Last Update Posted:
Oct 18, 2021
Last Verified:
Sep 1, 2021