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

  • End date
    Aug 17, 2023
  • participants needed
  • sponsor
    Daiichi Sankyo, Inc.
Updated on 20 October 2021


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).


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.

Condition Advanced Colorectal Cancer
Treatment DS-8201a 5.4 mg/kg Q3W, DS-8201a 6.4 mg/kg Q3W
Clinical Study IdentifierNCT04744831
SponsorDaiichi Sankyo, Inc.
Last Modified on20 October 2021


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

Participants who meet any of the following criteria will be disqualified from
entering the
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, Sjgren 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)
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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