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

NCT04744831 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: DS8201-A-U2072020-004782-39
• Study Type: interventional
• Target: 122
• Locations: 10 countries
• Sites: 63

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).

Conditions

Advanced Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; HER2 Overexpressing Colorectal Cancer; BRAF Wild-Type Status; DS-8201a; Trastuzumab deruxtecan; Advanced Colorectal Cancer; T-DXd

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (11)

• 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

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

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

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

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

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

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

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

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

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

Other Outcomes (7)

• Change From Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30)

  From baseline to data cut off, up to approximately 19 months.

• Change From Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Colorectal Cancer 29 (QLQ-CR29)

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

• Patient-Reported Outcomes (PROs) in the EuroQol Questionnaire (EQ) of 5 Dimensions (5D) on a Standardized 5- Level (5L) Descriptive Health Status Scale (EQ-5D-5L)

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

Study Arms (2)

T-DXd 5.4 mg/kg Q3W

EXPERIMENTAL

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

Drug: DS-8201a 5.4 mg/kg Q3W

T-DXd 6.4 mg/kg Q3W

EXPERIMENTAL

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

Drug: DS-8201a 6.4 mg/kg Q3W

Interventions

DS-8201a 5.4 mg/kg Q3W DRUG

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

Also known as: T-DXd

T-DXd 5.4 mg/kg Q3W

DS-8201a 6.4 mg/kg Q3W DRUG

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

Also known as: T-DXd

T-DXd 6.4 mg/kg Q3W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Daiichi Sankyo: lead
• AstraZeneca: collaborator

Study Sites (63)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Norton Cancer Institute Audubon

Louisville, Kentucky, 40217, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Sarah Cannon (Tennessee Oncology - Nashville)

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Flinders Medical Centre (FMC)

Bedford Park, Australia

Location

Blacktown Hospital

Blacktown, Australia

Location

Royal Brisbane & Women's Hospital

Brisbane, Australia

Location

Monash Medical Centre

Clayton, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Australia

Location

UCL St-Luc

Brussels, Belgium

Location

UZ Antwerpen

Edegem, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Hopital Jean Minjoz

Besançon, France

Location

Hopital Edouard Herriot

Lyon, France

Location

ICM-Val d'Aurelle

Montpellier, France

Location

University Hospital of nantes

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Hopital St Antoine

Paris, France

Location

Centre de Lutte Contre le Cancer CLCC - Institut Curie

Saint-Cloud, France

Location

Chu Toulouse

Toulouse, France

Location

Asst Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Istituto Oncologico Veneto Irccs

Padua, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

Aienda Ospedaliera San Camillo Forlanini

Rome, Italy

Location

Azienda ULSS 8 Berica

Vicenza, Italy

Location

Aichi Cancer Center Hospital

Aichi, Japan

Location

National Cancer Center Hospital East

Chiba, Japan

Location

National Hospital Organization Shikoku Cancer Center

Ehime, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan

Location

Hokkaido University Hospital

Hokkaido, Japan

Location

Kanagawa Cancer Center

Kanagawa, Japan

Location

Kindai University Hospital

Osaka, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, Japan

Location

National Cancer Center (NCC)

Goyang-si, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, South Korea

Location

Hospital Clinico y Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall dHebron

Barcelona, Spain

Location

Clinica Universitaria de Navarra - Madrid

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital KMUH

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

Taoyuan District, Taiwan

Location

Chang Gung Memorial Hospital-LinKou

Taoyuan District, Taiwan

Location

Beatson Glasgow

Glasgow, United Kingdom

Location

The Royal Marsden Hospital

London, United Kingdom

Location

UCLH Trust

London, United Kingdom

Location

The Christie

Manchester, United Kingdom

Location

The Royal Marsden Hospital

Sutton, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 41487064 DERIVED

• 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.

  PMID: 39116902 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sanyko, Inc

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: February 9, 2021
• Study Start: March 5, 2021
• Primary Completion: November 1, 2022
• Study Completion: December 4, 2024
• Last Updated: January 14, 2026
• Results First Posted: January 2, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (9); BE (3); IT (6); ES (5); TW (6); KR (6); JP (10); FR (8); GB (5); AU (5)