Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer
- Conditions
- Advanced Colorectal Cancer
- Interventions
- Registration Number
- NCT04744831
- Lead Sponsor
- Daiichi Sankyo
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 122
Participants must meet all of the following criteria to be eligible for randomization/registration into the study:
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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.
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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
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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) +.
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Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
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Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
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Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.
KEY
Participants who meet any of the following criteria will be disqualified from entering the study:
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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.
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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).
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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.
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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.).
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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.
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Prior pneumonectomy.
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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.
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Participants with leptomeningeal carcinomatosis.
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Has known human immunodeficiency virus (HIV) infection.
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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).
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Previous treatment with a DXd-containing antibody-drug conjugate (ADC).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description T-DXd 6.4 mg/kg Q3W DS-8201a 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). T-DXd 5.4 mg/kg Q3W DS-8201a 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).
- Primary Outcome Measures
Name Time Method 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 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
Name Time Method Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody Baseline up to 40 months Patient-Reported Outcomes (PROs) in Patient Global Impression of Change (PGIC) Scores Baseline up to 40 months Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer 6 months post-dose administration to data cut off, up to 40 months Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer 6 months post-dose administration to data cut off, up to 40 months Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer 6 months post-dose administration to data cut off, up to 40 months 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) Baseline up to 40 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) Baseline up to 40 months Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT) Baseline up to 40 months Serum Concentration of Active Metabolite MAAA-1181a Baseline up to 40 months 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 6 months post-dose administration to data cut off, up to 40 months Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer 6 months post-dose administration to data cut off, up to 40 months Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer 6 months post-dose administration to data cut off, up to 40 months 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 Baseline up to 40 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) Baseline up to 40 months Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS) Baseline up to 40 months Inpatient Healthcare Resource Utilization Baseline up to 40 months Serum Concentration of T-DXd Baseline up to 40 months Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd Baseline up to 40 months
Trial Locations
- Locations (62)
The University of Chicago
🇺🇸Chicago, Illinois, 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
Hopital Jean Minjoz
🇫🇷Besançon, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Centre de Lutte Contre le Cancer CLCC - Institut Curie
🇫🇷Saint-Cloud, France
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Aienda Ospedaliera San Camillo Forlanini
🇮🇹Rome, Italy
Clinica Universitaria de Navarra - Madrid
🇪🇸Madrid, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital KMUH
🇨🇳Kaohsiung, Taiwan
Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
🇨🇳Taoyuan, Taiwan
Beatson Glasgow
🇬🇧Glasgow, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
UCLH Trust
🇬🇧London, United Kingdom
Norton Cancer Institute Audubon
🇺🇸Louisville, Kentucky, 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
🇧🇪Bruxelles, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Hopital Edouard Herriot
🇫🇷Lyon Cedex 03, France
ICM-Val d'Aurelle
🇫🇷MONTPELLIER Cedex 5, France
University Hospital of nantes
🇫🇷Nantes, France
Hopital St Antoine
🇫🇷Paris, France
Chu Toulouse
🇫🇷Toulouse, France
Asst Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Istituto Oncologico Veneto Irccs
🇮🇹Padova, 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
The Christie
🇬🇧Manchester, United Kingdom
National Cancer Center Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
National Cancer Center (NCC)
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Clinico y Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall dHebron
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital-LinKou
🇨🇳Taoyuan, Taiwan