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

NCT ID: NCT04744831

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-05
• Study Completion Date: 2024-12-04

Brief 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).

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.

Conditions

Advanced Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

T-DXd 5.4 mg/kg Q3W

Participants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Group Type: EXPERIMENTAL

DS-8201a 5.4 mg/kg Q3W

Intervention Type: DRUG

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

T-DXd 6.4 mg/kg Q3W

Participants will be randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).

Group Type: EXPERIMENTAL

DS-8201a 6.4 mg/kg Q3W

Intervention Type: DRUG

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

Interventions

DS-8201a 5.4 mg/kg Q3W

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

Intervention Type: DRUG

DS-8201a 6.4 mg/kg Q3W

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

Intervention Type: DRUG

Other Intervention Names

T-DXd; T-DXd

Eligibility Criteria

Inclusion Criteria

Participants must meet all of the following criteria to be eligible for randomization/registration into the study:

1. 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.

2. 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.

3. The following therapies should be included in prior lines of therapy:

1. Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated

2. Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated

3. Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated

4. 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

4. 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) +.

5. Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.

6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

7. Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.

Exclusion Criteria

Participants who meet any of the following criteria will be disqualified from entering the study:

1. 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.

2. 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).

3. 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.

4. 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.).

5. 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.

6. Prior pneumonectomy.

7. 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.

8. Participants with leptomeningeal carcinomatosis.

9. Has known human immunodeficiency virus (HIV) infection.

10. 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).

11. Previous treatment with a DXd-containing antibody-drug conjugate (ADC).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

The University of Chicago

Chicago, Illinois, United States

Norton Cancer Institute Audubon

Louisville, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Sarah Cannon (Tennessee Oncology - Nashville)

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Flinders Medical Centre (FMC)

Bedford Park, , Australia

Blacktown Hospital

Blacktown, , Australia

Royal Brisbane & Women's Hospital

Brisbane, , Australia

Monash Medical Centre

Clayton, , Australia

Peter MacCallum Cancer Centre

Melbourne, , Australia

UCL St-Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Hopital Jean Minjoz

Besançon, , France

Hopital Edouard Herriot

Lyon, , France

ICM-Val d'Aurelle

Montpellier, , France

University Hospital of nantes

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

Hopital St Antoine

Paris, , France

Centre de Lutte Contre le Cancer CLCC - Institut Curie

Saint-Cloud, , France

Chu Toulouse

Toulouse, , France

Asst Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Istituto Oncologico Veneto Irccs

Padua, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Aienda Ospedaliera San Camillo Forlanini

Rome, , Italy

Azienda ULSS 8 Berica

Vicenza, , Italy

Aichi Cancer Center Hospital

Aichi, , Japan

National Cancer Center Hospital East

Chiba, , Japan

National Hospital Organization Shikoku Cancer Center

Ehime, , Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

Hokkaido University Hospital

Hokkaido, , Japan

Kanagawa Cancer Center

Kanagawa, , Japan

Kindai University Hospital

Osaka, , Japan

National Hospital Organization Osaka National Hospital

Osaka, , Japan

National Cancer Center Hospital

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

National Cancer Center (NCC)

Goyang-si, , South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Hospital Clinico y Provincial de Barcelona

Barcelona, , Spain

Hospital Universitari Vall dHebron

Barcelona, , Spain

Clinica Universitaria de Navarra - Madrid

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Clinica Universitaria de Navarra

Pamplona, , Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital KMUH

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

Taoyuan District, , Taiwan

Chang Gung Memorial Hospital-LinKou

Taoyuan District, , Taiwan

Beatson Glasgow

Glasgow, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

UCLH Trust

London, , United Kingdom

The Christie

Manchester, , United Kingdom

The Royal Marsden Hospital

Sutton, , United Kingdom

Countries

United States; Australia; Belgium; France; Italy; Japan; South Korea; Spain; Taiwan; United Kingdom

References

Raghav K. Trastuzumab deruxtecan in HER2-positive advanced colorectal cancer: a plain language summary of the DESTINY-CRC02 study. Future Oncol. 2026 Jan 5:1-13. doi: 10.1080/14796694.2025.2606418. Online ahead of print.

Reference Type: DERIVED

PMID: 41487064 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39116902 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-004782-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DS8201-A-U207

Identifier Type: -

Identifier Source: org_study_id