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Advanced Colorectal CancerPhase 2DESTINY-CRC02NCT04744831

Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer

A Phase 2 study testing DS-8201a 5.4 mg/kg Q3W and DS-8201a 6.4 mg/kg Q3W in people with Advanced Colorectal Cancer, run by Daiichi Sankyo at 63 sites in 10 countries.

Completed

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

Official record
Search all trials

Trial summary

This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Colorectal Cancer
What is being tested?
DS-8201a 5.4 mg/kg Q3W and DS-8201a 6.4 mg/kg Q3W
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
122 participants
Where
63 sitesin 10 countries
Study dates
5 Mar 2021to 4 Dec 2024
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

  • Participants must meet all of the following criteria to be eligible for randomization/registration into the study:
  • Adults aged ≥20 years in Japan, Taiwan, and Korea, or those aged ≥18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed.
  • Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site.
  • The following therapies should be included in prior lines of therapy:
  • Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
  • Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated
Show all 12Show fewer
  • Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated
  • Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated
  • Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +.
  • Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.

Who cannot join

  • Participants who meet any of the following criteria will be disqualified from entering the study:
  • Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI.
  • Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs).
  • Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
  • Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.).
  • Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening.
Show all 13Show fewer
  • Prior pneumonectomy.
  • Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiotherapy and randomization/registration.
  • Participants with leptomeningeal carcinomatosis.
  • Has known human immunodeficiency virus (HIV) infection.
  • Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+).
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
  • Previous treatment with a DXd-containing antibody-drug conjugate (ADC).

Trial locations and contacts

63 sites in 10 countries.

63 sites in 10 countries

Japan10 sites

  • Aichi Cancer Center Hospital

    Aichi

  • National Cancer Center Hospital East

    Chiba

  • National Hospital Organization Shikoku Cancer Center

    Ehime

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka

  • Hokkaido University Hospital

    Hokkaido

  • Kanagawa Cancer Center

    Kanagawa

  • Kindai University Hospital

    Osaka

  • National Hospital Organization Osaka National Hospital

    Osaka

  • National Cancer Center Hospital

    Tokyo

  • The Cancer Institute Hospital of JFCR

    Tokyo

Other trials in Japan

United States9 sites

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • The University of Chicago

    Chicago, Illinois, 60637

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Norton Cancer Institute Audubon

    Louisville, Kentucky, 40217

  • Sarah Cannon (Tennessee Oncology - Nashville)

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center (MSKCC)

    New York, New York, 10065

Other trials in United States

France8 sites

  • Hopital Jean Minjoz

    Besançon

  • Hopital Edouard Herriot

    Lyon

  • ICM-Val d'Aurelle

    Montpellier

  • University Hospital of nantes

    Nantes

  • Centre Antoine Lacassagne

    Nice

  • Hopital St Antoine

    Paris

  • Centre de Lutte Contre le Cancer CLCC - Institut Curie

    Saint-Cloud

  • Chu Toulouse

    Toulouse

Other trials in France

Italy6 sites

  • Asst Grande Ospedale Metropolitano Niguarda

    Milan

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

  • Istituto Oncologico Veneto Irccs

    Padova

  • Azienda Ospedaliero Universitaria Pisana

    Pisa

  • Aienda Ospedaliera San Camillo Forlanini

    Rome

  • Azienda ULSS 8 Berica

    Vicenza

Other trials in Italy

South Korea6 sites

  • National Cancer Center (NCC)

    Goyang-si

  • Seoul National University Bundang Hospital

    Gyeonggi-do

  • Asan Medical Center

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital Yonsei University Health System

    Seoul

Other trials in South Korea

Taiwan6 sites

  • Kaohsiung Medical University Chung-Ho Memorial Hospital KMUH

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • National Cheng Kung University Hospital

    Tainan

  • National Taiwan University Hospital

    Taipei

  • Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

    Taoyuan

  • Chang Gung Memorial Hospital-LinKou

    Taoyuan

Other trials in Taiwan

Australia5 sites

  • Flinders Medical Centre (FMC)

    Bedford Park

  • Blacktown Hospital

    Blacktown

  • Royal Brisbane & Women's Hospital

    Brisbane

  • Monash Medical Centre

    Clayton

  • Peter MacCallum Cancer Centre

    Melbourne

Other trials in Australia

Spain5 sites

  • Hospital Clinico y Provincial de Barcelona

    Barcelona

  • Hospital Universitari Vall dHebron

    Barcelona

  • Clinica Universitaria de Navarra - Madrid

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Clinica Universitaria de Navarra

    Pamplona

Other trials in Spain

United Kingdom5 sites

  • Beatson Glasgow

    Glasgow

  • The Royal Marsden Hospital

    London

  • UCLH Trust

    London

  • The Christie

    Manchester

  • The Royal Marsden Hospital

    Sutton

Other trials in United Kingdom

Belgium3 sites

  • UCL St-Luc

    Brussels

  • UZ Antwerpen

    Edegem

  • Universitair Ziekenhuis Gent

    Ghent

Other trials in Belgium

About this study

Official title: A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)

This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC).

Read the detailed description

This 2-stage study will evaluate participants with locally advanced, unresectable, or metastatic HER2-overexpressing colorectal cancer (CRC) (immunohistochemistry [IHC] 3+ or IHC 2+/ in situ hybridization [ISH]+) of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type and either rat sarcoma viral oncogenes homologue (RAS) wild-type or mutant tumor type, previously treated with standard therapy. In the first stage, participants will be randomized 1:1 with 2 doses of T-DXd. After Stage 1 enrollment is complete, all further eligible participants will be registered to T-DXd administered IV in Stage 2. Participants will receive the assigned dose of T-DXd until progression of disease or the participant meets one of the discontinuation criteria.

Being tested
DS-8201a 5.4 mg/kg Q3W, DS-8201a 6.4 mg/kg Q3W
Keywords
Metastatic Colorectal Cancer, HER2 Overexpressing Colorectal Cancer, BRAF Wild-Type Status, DS-8201a, Trastuzumab deruxtecan, Advanced Colorectal Cancer, T-DXd
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • DS-8201a 5.4 mg/kg Q3WDrug

    Also called T-DXd

    DS-8201a for injection will be administered intravenously (IV) at a dose of 5.4 mg/kg every 3 weeks (Q3W)

  • DS-8201a 6.4 mg/kg Q3WDrug

    Also called T-DXd

    DS-8201a for injection will be administered intravenously (IV) at a dose of 6.4 mg/kg every 3 weeks (Q3W)

Study groups in NCT04744831
Study groupRoleWhat they receive
T-DXd 5.4 mg/kg Q3WExperimentalParticipants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).
Receives: Drug: DS-8201a 5.4 mg/kg Q3W
T-DXd 6.4 mg/kg Q3WExperimentalParticipants will be randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
Receives: Drug: DS-8201a 6.4 mg/kg Q3W

What is being measured

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

  1. Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer

    Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

    Measured: 6 months post-dose administration to data cut off, up to 20 months

Secondary outcomes (11)

  1. Confirmed Objective Response Rate by Investigator Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer

    Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by Investigator assessment based on RECIST version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. ORR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From first dose administration to data cut off, up to approximately 19 months

  2. Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer

    DoR, defined as time from the initial response (CR or PR) by BICR and Investigator assessment until documented tumor progression or death from any cause. DoR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From the first documented evidence of a response (complete or partial) until disease progression or death, up to approximately 19 months.

  3. Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer

    Disease Control Rate (DCR), defined as the proportion of subjects who achieved CR, PR, or SD for a minimum of 6 weeks during study treatment; DCR based on BICR and DCR based on Investigator assessments assessed according to RECIST version 1.1. DCR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From first dose administration to data cut off, up to approximately 19 months.

  4. Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer

    Clinical Benefit Rate (CBR), defined as proportion of subjects who achieved CR, PR, or SD for at least 6 months; CBR based on BICR and CBR based on Investigator assessments will both be determined based on RECIST version 1.1. CBR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From first dose administration to data cut off, up to approximately 19 months.

  5. Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer

    Progression Free Survival (PFS) defined as the time from date of randomization/registration until first objective radiographic tumor progression or death from any cause, based on BICR and Investigator assessment according to RECIST version 1.1. PFS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From randomization to data cut off, up to approximately 19 months.

  6. Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer

    Overall Survival (OS) defined as the time from date of randomization/ registration until death from any cause, according to RECIST version 1.1. OS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From randomization to data cut off, up to approximately 19 months.

  7. Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer

    A Treatment-emergent Adverse Events (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug. Serious AEs with an onset or worsening 48 days or more after the last dose of study drug, if considered related to study treatment. are also TEAEs. TEAEs were assessed in the Safety Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From first dose administration to data cut off, up to approximately 19 months.

  8. Serum Concentration of T-DXd

    Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)

  9. Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody

    Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)

  10. Serum Concentration of Active Metabolite MAAA-1181a

    Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)

  11. Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd

    Immunogenicity will be assessed through characterization of incidence and titer of Anti-drug Antibodies (ADAs), the number and percentage of subjects positive for NAb of T-DXd by dose level will also be determined. ADAs and NAbs were assessed in the Immunogenicity Analysis Set at data cut-off date of 01 Nov 2022.

    Measured: From baseline to data cut off, up to approximately 19 months

Timeline

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

  1. First posted9 Feb 2021
  2. Study start5 Mar 2021
  3. Primary completion1 Nov 2022
  4. Study completion4 Dec 2024

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
122 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04744831
Sponsor's protocol ID
DS8201-A-U207
Other IDs
2020-004782-39
Acronym
DESTINY-CRC02
Status last verified
Dec 2025
First submitted
19 Jan 2021
Last updated
14 Jan 2026
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

  • Raghav K. Trastuzumab deruxtecan in HER2-positive advanced colorectal cancer: a plain language summary of the DESTINY-CRC02 study. Future Oncol. 2026 Jan;22(2):123-135. doi: 10.1080/14796694.2025.2606418. Epub 2026 Jan 5.

    PubMed 41487064

  • Raghav K, Siena S, Takashima A, Kato T, Van den Eynde M, Pietrantonio F, Komatsu Y, Kawakami H, Peeters M, Andre T, Lonardi S, Yamaguchi K, Tie J, Castro CG, Hsu HC, Strickler JH, Kim TY, Cha Y, Barrios D, Yan Q, Kamio T, Kobayashi K, Boran A, Koga M, Allard JD, Yoshino T. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol. 2024 Sep;25(9):1147-1162. doi: 10.1016/S1470-2045(24)00380-2. Epub 2024 Aug 5.

    PubMed 39116902

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DS-8201a 5.4 mg/kg Q3W and DS-8201a 6.4 mg/kg Q3W in people with Advanced Colorectal Cancer, run by Daiichi Sankyo at 63 sites in 10 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 12 inclusion and 13 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 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in Japan, United States, France, Italy, South Korea and 5 more countries. 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 2 Jan 2024). 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?

Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer (time frame: 6 months post-dose administration to data cut off, up to 20 months). 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 NCT04744831, which also lists 2 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 14 Jan 2026.

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