Colorectal NeoplasmPhase 2NCT03384940

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

A Phase 2 study testing DS-8201a in people with Colorectal Neoplasm, run by Daiichi Sankyo Co., Ltd. at 25 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Neoplasm
What is being tested?: DS-8201a
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 86 participants
Where: 25 sitesin 5 countries
Study dates: 23 Feb 2018to 10 Nov 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

25 sites in 5 countries.

Country

City, postcode or hospital

25 sites in 5 countries

United States9 sites

Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope Medical Center
Duarte, California, 91010
West Cancer Center
Germantown, Tennessee, 38138
Greenville Health System Cancer Institute
Greenville, South Carolina, 29605-4255
MD Anderson Cancer Center, University of Texas
Houston, Texas, 77030-4000
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224-1865
University of Southern California
Los Angeles, California, 90089
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
UCLA Health
Santa Monica, California, 90404

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Japan7 sites

National Hospital Organization Kyushu Cancer Center
Fukuoka, 811-1395
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-Ku, Tokyo, 135-8550
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, 464-8681
Kindai University Hospital
Ōsaka-sayama, Osaka, 589-8511
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648

Other trials in Japan

Italy4 sites

ASST Grande Ospedale Metropolitano Niguarda
Milan, Lombardo, 20162
Fondazione IRCCS - Istituto Nazionale dei Tumori
Milan, 20133
Università degli studi della Campania L.Vanvitelli
Naples, Campania, 80131
Oncology Institute Veneto IOV-IRCCS
Padova, Ferrara, 35128

Other trials in Italy

Spain3 sites

Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitari Clinic de Barcelona
Barcelona, 08036
Clinica Universidad de Navarra
Pamplona, Navarre, 31008

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United Kingdom2 sites

Royal Marsden Institute (Chelsea)
Chelsea, London, England, SM2 5PT
Royal Marsden Institute (Sutton)
Sutton, Surrey, England, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Colorectal Cancer

The main objective of this study is to test the safety and effectiveness of DS-8201a for participants with HER2-expressing advanced colorectal cancer.

Read the 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.

Conditions: Colorectal Neoplasm
Being tested: DS-8201a
Keywords: Oncology, HER2, Colorectal cancer, Antibody drug conjugate, ADC
Medical subject headings: Colorectal Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DS-8201aDrug
Also called Trastuzumab deruxtecan
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

Study groups in NCT03384940
Study group	Role	What they receive
DS-8201a Cohort A	Experimental	Cohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks Receives: Drug: DS-8201a
DS-8201a Cohort B	Experimental	Cohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks Receives: Drug: DS-8201a
DS-8201a Cohort C	Experimental	Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks Receives: Drug: DS-8201a

What is being measured

The primary outcome is the main question the study is designed to answer.

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
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.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
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
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.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose

Secondary outcomes (14)

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
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.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
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
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.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
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
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.
Measured: 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
Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
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).
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
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
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.
Measured: 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 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
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.
Measured: Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
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
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
Measured: Time from the date of first dose to date of death from any cause, up to approximately 18 months
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
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.
Measured: Time from the date of first dose to date of death from any cause, up to approximately 18 months
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
Measured: 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
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Maximum serum concentration (Cmax) of MAAA-1181a was assessed.
Measured: 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
Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.
Measured: 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
Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
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.
Measured: 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
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
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.
Measured: 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
Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
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.
Measured: From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Feb 201810 Nov 2020

First posted28 Dec 2017
Study start23 Feb 2018
Primary completion9 Aug 2019
Study completion10 Nov 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Colorectal NeoplasmStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 86 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03384940
Sponsor's protocol ID: DS8201-A-J203
Other IDs: 2017-003466-28, 173808, DESTINY-C01, 2017
Status last verified: Sep 2021
First submitted: 20 Dec 2017
Last updated: 18 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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/

Publications

Siena S, Raghav K, Masuishi T, Yamaguchi K, Nishina T, Elez E, Rodriguez J, Chau I, Di Bartolomeo M, Kawakami H, Suto F, Koga M, Inaki K, Kuwahara Y, Takehara I, Barrios D, Kobayashi K, Grothey A, Yoshino T. HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01. Nat Commun. 2024 Nov 25;15(1):10213. doi: 10.1038/s41467-024-53223-3.
PubMed 39587050
Yoshino T, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Wainberg Z, Elez E, Rodriguez J, Fakih M, Ciardiello F, Saxena K, Kobayashi K, Bako E, Okuda Y, Meinhardt G, Grothey A, Siena S; DESTINY-CRC01 investigators. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023 Jun 7;14(1):3332. doi: 10.1038/s41467-023-38032-4.
PubMed 37286557
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.
PubMed 33961795

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Colorectal Cancer
ClinicalTrials.gov ID: NCT03384940
Acronym / sponsor ID: DS8201-A-J203
Conditions: Colorectal Neoplasm
Keywords: Oncology, HER2, Colorectal cancer, Antibody drug conjugate, ADC
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 86 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Collaborators: Daiichi Sankyo, AstraZeneca
Study start: 23 Feb 2018 (actual)
Primary completion: 9 Aug 2019 (actual)
Study completion: 10 Nov 2020 (actual)
First posted: 28 Dec 2017 (actual)
Results: Posted 24 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
DS-8201a Cohort A	Experimental	Drug: DS-8201aCohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks
DS-8201a Cohort B	Experimental	Drug: DS-8201aCohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks
DS-8201a Cohort C	Experimental	Drug: DS-8201aCohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DS-8201aAlso: Trastuzumab deruxtecanDS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration	Drug	DS-8201a Cohort A, DS-8201a Cohort B, DS-8201a Cohort C

Primary outcome

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.

14 secondary outcomes

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
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
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
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
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 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
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 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
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
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
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
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
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
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

Results and safety

Results posted to the registry on 24 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DS-8201a Cohort A	53	0
DS-8201a Cohort B	15	0
DS-8201a Cohort C	18	0

Primary outcome: 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. Count of participants. Unit: Participants

Measure	DS-8201a Cohort A n = 53	DS-8201a Cohort B n = 15	DS-8201a Cohort C n = 18
Confirmed CR	0	0	0
Confirmed PR	24	0	0
Confirmed SD	20	9	4
Confirmed PD	5	5	10
Confirmed Non-evaluable	4	1	4
Unconfirmed CR	0	0	0
Unconfirmed PR	26	0	0
Unconfirmed SD	18	9	4

Population analysed: Response was assessed in the Full Analysis Set.

Primary outcome: 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. Count of participants. Unit: Participants

Measure	DS-8201a Cohort A n = 53	DS-8201a Cohort B n = 15	DS-8201a Cohort C n = 18
Confirmed CR+PR	24	0	0
Confirmed CR+PR (within 3 months)	10	0	0
Confirmed CR+PR (within 6 months)	23	0	0
Confirmed CR+PR (within 9 months)	24	0	0
Confirmed CR+PR (12 months)	24	0	0
Unconfirmed CR+PR	26	0	0
Unconfirmed CR+PR (within 3 months)	20	0	0
Unconfirmed CR+PR (within 6 months)	25	0	0

Population analysed: Response was assessed in the Full Analysis Set.

14 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DS-8201a Cohort A	20 of 53 (37.7%)	53 of 53 (100%)	36 of 53
DS-8201a Cohort B	6 of 15 (40%)	15 of 15 (100%)	10 of 15
DS-8201a Cohort C	9 of 18 (50%)	18 of 18 (100%)	12 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39587050Siena S, Raghav K, Masuishi T, Yamaguchi K, Nishina T, Elez E, Rodriguez J, Chau I, Di Bartolomeo M, Kawakami H, Suto F, Koga M, Inaki K, Kuwahara Y, Takehara I, Barrios D, Kobayashi K, Grothey A, Yoshino T. HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01. Nat Commun. 2024 Nov 25;15(1):10213. doi: 10.1038/s41467-024-53223-3.
Derived from this study: PubMed 37286557Yoshino T, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Wainberg Z, Elez E, Rodriguez J, Fakih M, Ciardiello F, Saxena K, Kobayashi K, Bako E, Okuda Y, Meinhardt G, Grothey A, Siena S; DESTINY-CRC01 investigators. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023 Jun 7;14(1):3332. doi: 10.1038/s41467-023-38032-4.
Derived from this study: PubMed 33961795Siena 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.
Individual participant dataSharing planned: Yes. 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/

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Leader study director

Daiichi Sankyo

25 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DS-8201a in people with Colorectal Neoplasm, run by Daiichi Sankyo Co., Ltd. at 25 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Japan, Italy, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03384940, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021.