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

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ClinicalTrials.gov Identifier: NCT03384940
Recruitment Status : Completed
First Posted : December 28, 2017
Results First Posted : August 24, 2021
Last Update Posted : August 24, 2021
Sponsor:
Collaborators:
Daiichi Sankyo, Inc.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Tracking Information
First Submitted Date  ICMJE December 20, 2017
First Posted Date  ICMJE December 28, 2017
Results First Submitted Date  ICMJE May 12, 2021
Results First Posted Date  ICMJE August 24, 2021
Last Update Posted Date August 24, 2021
Actual Study Start Date  ICMJE February 23, 2018
Actual Primary Completion Date August 9, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2021)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
Objective response rate (ORR) per imaging assessment [ Time Frame: from Cycle 1 Day 1 through disease progression (within 18 months) ]
Percentage of participants with objective response per independent central imaging facility review based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2021)
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2017)
  • Progression-free survival [ Time Frame: within 18 months ]
    Percentage of participants still alive without the disease getting worse
  • Overall survival (OS) [ Time Frame: at 18 months ]
    Percentage of participants still alive
  • Duration of response [ Time Frame: within 18 months ]
    Length of time response continued
  • Disease control rate (DCR) [ Time Frame: within 18 months ]
    Percentage of participants with controlled disease
  • ORR assessed by the investigator based on RECIST version 1.1 [ Time Frame: within 18 months ]
    Percentage of participants with objective response as assessed by the investigator, based on RECIST version 1.1
  • Maximum serum/plasma concentration (Cmax) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
  • Time to Cmax (Tmax) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
  • Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast) [ Time Frame: within 21 days ]
    Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
  • AUC from the time of dosing until day 21 (AUC0-21d) [ Time Frame: at Day 21 ]
    Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01)
Official Title  ICMJE A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Colorectal Cancer
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Neoplasm
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: DS-8201a
  • 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
    Intervention: Drug: DS-8201a
  • Experimental: DS-8201a Cohort C
    Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks
    Intervention: Drug: DS-8201a
Publications * Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779-789. doi: 10.1016/S1470-2045(21)00086-3. Epub 2021 May 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2021)
86
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2017)
90
Actual Study Completion Date  ICMJE November 10, 2020
Actual Primary Completion Date August 9, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Japan,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03384940
Other Study ID Numbers  ICMJE DS8201-A-J203
2017-003466-28 ( EudraCT Number )
173808 ( Registry Identifier: JAPIC CTI )
DESTINY-C01 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Responsible Party Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
Study Sponsor  ICMJE Daiichi Sankyo Co., Ltd.
Collaborators  ICMJE
  • Daiichi Sankyo, Inc.
  • AstraZeneca
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP