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Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer (DESTINY-CRC02)

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ClinicalTrials.gov Identifier: NCT04744831
Recruitment Status : Active, not recruiting
First Posted : February 9, 2021
Results First Posted : January 2, 2024
Last Update Posted : March 13, 2024
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo

Study Description
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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).

Condition or disease Intervention/treatment Phase
Advanced Colorectal Cancer Drug: DS-8201a 5.4 mg/kg Q3W Drug: DS-8201a 6.4 mg/kg Q3W Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 5, 2021
Actual Primary Completion Date : November 1, 2022
Estimated Study Completion Date : July 1, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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).
 Drug: 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)
Other Name: T-DXd
Experimental: 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).
 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)
Other Name: T-DXd


Outcome Measures
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Primary Outcome Measures :
  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 [ Time Frame: 6 months post-dose administration to data cut off, up to 20 months ]
    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.


Secondary Outcome Measures :
  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 [ Time Frame: 6 months post-dose administration to data cut off, up to 40 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 [ Time Frame: 6 months post-dose administration to data cut off, up to 40 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 [ Time Frame: 6 months post-dose administration to data cut off, up to 40 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 [ Time Frame: 6 months post-dose administration to data cut off, up to 40 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 [ Time Frame: 6 months post-dose administration to data cut off, up to 40 months ]
  6. Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer [ Time Frame: 6 months post-dose administration to data cut off, up to 40 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 [ Time Frame: Baseline up to 40 months ]
  8. 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) [ Time Frame: Baseline up to 40 months ]
  9. 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) [ Time Frame: Baseline up to 40 months ]
  10. 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) [ Time Frame: Baseline up to 40 months ]
  11. Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT) [ Time Frame: Baseline up to 40 months ]
  12. Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS) [ Time Frame: Baseline up to 40 months ]
  13. Patient-Reported Outcomes (PROs) in Patient Global Impression of Change (PGIC) Scores [ Time Frame: Baseline up to 40 months ]
  14. Inpatient Healthcare Resource Utilization [ Time Frame: Baseline up to 40 months ]
  15. Serum Concentration of T-DXd [ Time Frame: Baseline up to 40 months ]
  16. Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody [ Time Frame: Baseline up to 40 months ]
  17. Serum Concentration of Active Metabolite MAAA-1181a [ Time Frame: Baseline up to 40 months ]
  18. Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd [ Time Frame: Baseline up to 40 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

KEY 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.

KEY 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04744831


Locations
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Sponsors and Collaborators
Daiichi Sankyo
AstraZeneca
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo:
Study Protocol and Statistical Analysis Plan  [PDF] October 29, 2020

More Information
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Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT04744831    
Other Study ID Numbers: DS8201-A-U207
2020-004782-39 ( EudraCT Number )
First Posted: February 9, 2021    Key Record Dates
Results First Posted: January 2, 2024
Last Update Posted: March 13, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.
URL: http://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo:
Metastatic Colorectal Cancer
HER2 Overexpressing Colorectal Cancer
BRAF Wild-Type Status
DS-8201a
 Trastuzumab deruxtecan
Advanced Colorectal Cancer
T-DXd
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
 Camptothecin
Trastuzumab deruxtecan
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action