We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03384940
Recruitment Status : Completed
First Posted : December 28, 2017
Results First Posted : August 24, 2021
Last Update Posted : October 18, 2021
Sponsor:
Collaborators:
Daiichi Sankyo, Inc.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Colorectal Neoplasm Drug: DS-8201a 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : February 23, 2018
Actual Primary Completion Date : August 9, 2019
Actual Study Completion Date : November 10, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: Trastuzumab deruxtecan
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 Name: Trastuzumab deruxtecan
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 Name: Trastuzumab deruxtecan


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 [ Time Frame: 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.

  2. 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 [ Time Frame: 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 :
  1. 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 [ Time Frame: 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.

  2. 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 [ Time Frame: 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.

  3. 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 [ 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 ]
    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.

  4. Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer [ Time Frame: 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).

  5. 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 [ Time Frame: 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.

  6. 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 [ Time Frame: 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.

  7. 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 Frame: 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.

  8. 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 Frame: 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.

  9. Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [ 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 ]
    Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.

  10. Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [ 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 ]
    Maximum serum concentration (Cmax) of MAAA-1181a was assessed.

  11. Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [ 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 ]
    Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.

  12. Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [ 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 ]
    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.

  13. 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 [ 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 ]
    Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.

  14. Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer [ Time Frame: 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03384940


Locations
Show Show 25 study locations
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo, Inc.
AstraZeneca
Investigators
Layout table for investigator information
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Study Protocol and Statistical Analysis Plan  [PDF] July 3, 2020

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT03384940    
Other Study ID Numbers: DS8201-A-J203
2017-003466-28 ( EudraCT Number )
173808 ( Registry Identifier: JAPIC CTI )
DESTINY-C01 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
First Posted: December 28, 2017    Key Record Dates
Results First Posted: August 24, 2021
Last Update Posted: October 18, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Oncology
HER2
Colorectal cancer
Antibody drug conjugate
ADC
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
 Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents