Clinical trial NCT04744831: Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2021-02-09
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: 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
timeFrame: 6 months post-dose administration to data cut off, up to 20 months
Secondary outcomes:
measure: 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
timeFrame: 6 months post-dose administration to data cut off, up to 40 months
measure: Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
timeFrame: 6 months post-dose administration to data cut off, up to 40 months
measure: Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer
timeFrame: 6 months post-dose administration to data cut off, up to 40 months
measure: Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer
timeFrame: 6 months post-dose administration to data cut off, up to 40 months
measure: Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
timeFrame: 6 months post-dose administration to data cut off, up to 40 months
measure: Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
timeFrame: 6 months post-dose administration to data cut off, up to 40 months
measure: 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
timeFrame: Baseline up to 40 months
measure: 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)
timeFrame: Baseline up to 40 months
measure: 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)
timeFrame: Baseline up to 40 months
measure: 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)
timeFrame: Baseline up to 40 months
measure: Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT)
timeFrame: Baseline up to 40 months
measure: Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS)
timeFrame: Baseline up to 40 months
measure: Patient-Reported Outcomes (PROs) in Patient Global Impression of Change (PGIC) Scores
timeFrame: Baseline up to 40 months
measure: Inpatient Healthcare Resource Utilization
timeFrame: Baseline up to 40 months
measure: Serum Concentration of T-DXd
timeFrame: Baseline up to 40 months
measure: Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody
timeFrame: Baseline up to 40 months
measure: Serum Concentration of Active Metabolite MAAA-1181a
timeFrame: Baseline up to 40 months
measure: Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd
timeFrame: Baseline up to 40 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute Audubon
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (MSKCC)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon (Tennessee Oncology - Nashville)
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Bedford Park
country: Australia
facility: Flinders Medical Centre (FMC)
city: Blacktown
country: Australia
facility: Blacktown Hospital
city: Brisbane
country: Australia
facility: Royal Brisbane & Women's Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Bruxelles
country: Belgium
facility: UCL St-Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Besançon
country: France
facility: Hopital Jean Minjoz
city: Lyon Cedex 03
country: France
facility: Hopital Edouard Herriot
city: MONTPELLIER Cedex 5
country: France
facility: ICM-Val d'Aurelle
city: Nantes
country: France
facility: University Hospital of nantes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital St Antoine
city: Saint-Cloud
country: France
facility: Centre de Lutte Contre le Cancer CLCC - Institut Curie
city: Toulouse
country: France
facility: Chu Toulouse
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Istituto Oncologico Veneto Irccs
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rome
country: Italy
facility: Aienda Ospedaliera San Camillo Forlanini
city: Vicenza
country: Italy
facility: Azienda ULSS 8 Berica
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Ehime
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center (NCC)
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Barcelona
country: Spain
facility: Hospital Clinico y Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall dHebron
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital KMUH
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital-LinKou
city: Glasgow
country: United Kingdom
facility: Beatson Glasgow
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: London
country: United Kingdom
facility: UCLH Trust
city: Manchester
country: United Kingdom
facility: The Christie
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: