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

  • End date
    Aug 28, 2023
  • participants needed
  • sponsor
    Daiichi Sankyo, Inc.
Updated on 29 December 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 on29 December 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
The following therapies should be included in prior lines of therapy
Pathologically-documented, unresectable, recurrent, or metastatic colorectal
Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue
B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status
Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated
identified in primary or metastatic site
Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
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
Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before

Exclusion Criteria

Prior pneumonectomy
Participants with leptomeningeal carcinomatosis
Participants who meet any of the following criteria will be disqualified from entering the
Has known human immunodeficiency virus (HIV) infection
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
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
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)
Clear my responses

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