Advanced Colorectal Cancer
Conditions
Keywords
Metastatic Colorectal Cancer, HER2 Overexpressing Colorectal Cancer, BRAF Wild-Type Status, DS-8201a, Trastuzumab deruxtecan, Advanced Colorectal Cancer, T-DXd
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.
Interventions
DRUGDS-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)
DRUGDS-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)
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | From first dose administration to data cut off, up to approximately 19 months. | Disease Control Rate (DCR), defined as the proportion of subjects who achieved CR, PR, or SD for a minimum of 6 weeks during study treatment; DCR based on BICR and DCR based on Investigator assessments assessed according to RECIST version 1.1. DCR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
| Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | From randomization to data cut off, up to approximately 19 months. | Progression Free Survival (PFS) defined as the time from date of randomization/registration until first objective radiographic tumor progression or death from any cause, based on BICR and Investigator assessment according to RECIST version 1.1. PFS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
| Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | From randomization to data cut off, up to approximately 19 months. | Overall Survival (OS) defined as the time from date of randomization/ registration until death from any cause, according to RECIST version 1.1. OS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
| 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 | From first dose administration to data cut off, up to approximately 19 months. | A Treatment-emergent Adverse Events (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug. Serious AEs with an onset or worsening 48 days or more after the last dose of study drug, if considered related to study treatment. are also TEAEs. TEAEs were assessed in the Safety Analysis Set at data cut-off date of 01 Nov 2022. |
| Serum Concentration of T-DXd | C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI) | Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022. |
| Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI) | Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022. |
| Serum Concentration of Active Metabolite MAAA-1181a | C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI) | Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022. |
| Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd | From baseline to data cut off, up to approximately 19 months | Immunogenicity will be assessed through characterization of incidence and titer of Anti-drug Antibodies (ADAs), the number and percentage of subjects positive for NAb of T-DXd by dose level will also be determined. ADAs and NAbs were assessed in the Immunogenicity Analysis Set at data cut-off date of 01 Nov 2022. |
| 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 | From first dose administration to data cut off, up to approximately 19 months | Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by Investigator assessment based on 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. ORR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
| Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | From the first documented evidence of a response (complete or partial) until disease progression or death, up to approximately 19 months. | DoR, defined as time from the initial response (CR or PR) by BICR and Investigator assessment until documented tumor progression or death from any cause. DoR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
| Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | From first dose administration to data cut off, up to approximately 19 months. | Clinical Benefit Rate (CBR), defined as proportion of subjects who achieved CR, PR, or SD for at least 6 months; CBR based on BICR and CBR based on Investigator assessments will both be determined based on RECIST version 1.1. CBR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) | From baseline to data cut off, up to approximately 19 months | Exploratory outcome, results not included in this submission. The EQ-5D-5L is self-administered and consists of 2 parts, the EQ-5D-5L descriptive system and the EQ-visual analogue scale. On each dimension, a score of 1 indicates no patient problems in that dimension, 2 indicates slight problems in that dimension, 3 indicates moderate problems in that dimension, 4 indicates severe problems in that dimension and 5 indicates extreme problems in that dimension. |
| Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT) | From baseline to data cut off, up to approximately 19 months | Exploratory outcome, results not included in this submission. The PGI-TT item is included to assess how a patient perceives the overall tolerability of the study treatment over the past 7 days. This is a single-item questionnaire, and patients will rate the bother associated with any treatment-related symptoms using response options ranging from Not at all to Very much. |
| Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS) | From baseline to data cut off, up to approximately 19 months | Exploratory outcome, results not included in this submission. The PGIS item is included to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. This is a single-item questionnaire, and patients will choose the response that best describes the severity of their overall cancer symptoms with options ranging from No Symptoms to Very Severe. |
| Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIC) | From baseline to data cut off, up to approximately 19 months | Exploratory outcome, results not included in this submission. The PGIC item is included to assess how a patient perceives their overall change in health status since the start of study treatment. This is a single-item questionnaire, and patients will choose from response options ranging from Much Better to Much Worse. |
| Inpatient Healthcare Resource Utilization | From baseline to data cut off, up to approximately 19 months | Exploratory outcome, results not included in this submission. The impact of treatment and disease on healthcare resource use (including inpatient admissions, intensive care unit admissions, and length of stay in hospital) will be captured/collected in this study on an event-driven basis. |
| 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) | From baseline to data cut off, up to approximately 19 months. | Exploratory outcome, results not included in this submission. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items and no item occurs in more than 1 scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Patient questionnaires were assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022. |
| 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) | From baseline to data cut off, up to approximately 19 months | Exploratory outcome, results not included in this submission. EORTC QLQ-CR29 is designed to be administered in addition to EORTC QLQ-C30. The EORTC QLQ-CR29 is a specific questionnaire for Colorectal Cancer. Scale from 0 to 100, A higher scale represents better function and a higher quality of life. |
Countries
Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 122 participants who met all inclusion criteria and no exclusion criteria were randomized/registered to T-DXd treatment in the United States, Asia-Pacific, and Europe.
Pre-assignment details
Following adequate study explanation by the investigator or their designee, subjects voluntarily offered signed, informed consent prior to participation in any study procedures.
Participants by arm
| Arm | Count |
|---|---|
| T-DXd 5.4 mg/kg Q3W Participants were randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W). | 82 |
| T-DXd 6.4 mg/kg Q3W Participants were randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W). | 40 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 |
| Overall Study | Clinical Progression | 5 | 5 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Other | 5 | 1 |
| Overall Study | Progressive Disease | 63 | 29 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | T-DXd 5.4 mg/kg Q3W | T-DXd 6.4 mg/kg Q3W | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 17 Participants | 45 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 23 Participants | 77 Participants |
| Age, Continuous | 58.5 years STANDARD_DEVIATION 13.05 | 61.1 years STANDARD_DEVIATION 12.13 | 59.3 years STANDARD_DEVIATION 12.77 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 42 Participants | 24 Participants | 66 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 35 Participants | 15 Participants | 50 Participants |
| Sex: Female, Male Female | 37 Participants | 21 Participants | 58 Participants |
| Sex: Female, Male Male | 45 Participants | 19 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 26 / 83 | 13 / 39 |
| other Total, other adverse events | 81 / 83 | 38 / 39 |
| serious Total, serious adverse events | 21 / 83 | 12 / 39 |
Outcome results
Primary
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
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.
Time frame: 6 months post-dose administration to data cut off, up to 20 months
Population: ORR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T-DXd 5.4 mg/kg Q3W | 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 | 37.8 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | 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 | 27.5 percentage of participants |
Secondary
Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer
Clinical Benefit Rate (CBR), defined as proportion of subjects who achieved CR, PR, or SD for at least 6 months; CBR based on BICR and CBR based on Investigator assessments will both be determined based on RECIST version 1.1. CBR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From first dose administration to data cut off, up to approximately 19 months.
Population: CBR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | BICR | 45.1 percentage of participants |
| T-DXd 5.4 mg/kg Q3W | Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | Investigator | 51.2 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | BICR | 32.5 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | Investigator | 42.5 percentage of participants |
Secondary
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
Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by Investigator assessment based on 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. ORR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From first dose administration to data cut off, up to approximately 19 months
Population: ORR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T-DXd 5.4 mg/kg Q3W | 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 | 31.7 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | 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 | 30.0 percentage of participants |
Secondary
Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer
Disease Control Rate (DCR), defined as the proportion of subjects who achieved CR, PR, or SD for a minimum of 6 weeks during study treatment; DCR based on BICR and DCR based on Investigator assessments assessed according to RECIST version 1.1. DCR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From first dose administration to data cut off, up to approximately 19 months.
Population: DCR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | BICR | 86.6 percentage of participants |
| T-DXd 5.4 mg/kg Q3W | Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | Investigator | 89.0 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | BICR | 85.0 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer | Investigator | 85.0 percentage of participants |
Secondary
Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
DoR, defined as time from the initial response (CR or PR) by BICR and Investigator assessment until documented tumor progression or death from any cause. DoR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From the first documented evidence of a response (complete or partial) until disease progression or death, up to approximately 19 months.
Population: DoR was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | BICR | 5.5 months |
| T-DXd 5.4 mg/kg Q3W | Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | Investigator | 5.6 months |
| T-DXd 6.4 mg/kg Q3W | Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | BICR | 5.5 months |
| T-DXd 6.4 mg/kg Q3W | Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | Investigator | 6.9 months |
Secondary
Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Overall Survival (OS) defined as the time from date of randomization/ registration until death from any cause, according to RECIST version 1.1. OS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From randomization to data cut off, up to approximately 19 months.
Population: OS was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | 13.4 months |
| T-DXd 6.4 mg/kg Q3W | Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | NA months |
Secondary
Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd
Immunogenicity will be assessed through characterization of incidence and titer of Anti-drug Antibodies (ADAs), the number and percentage of subjects positive for NAb of T-DXd by dose level will also be determined. ADAs and NAbs were assessed in the Immunogenicity Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: The Immunogenicity Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of the study drug and who had at least~1 baseline or postbaseline immunogenicity assessment. Subjects were analyzed according to the treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd | ADA | 1.3 percentage of participants |
| T-DXd 5.4 mg/kg Q3W | Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd | NAb | 0 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd | ADA | 0 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd | NAb | 0 percentage of participants |
Secondary
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
A Treatment-emergent Adverse Events (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug. Serious AEs with an onset or worsening 48 days or more after the last dose of study drug, if considered related to study treatment. are also TEAEs. TEAEs were assessed in the Safety Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From first dose administration to data cut off, up to approximately 19 months.
Population: The Safety Analysis Set (SAS) included all randomized/registered subjects who received at least 1 dose of study treatment. Subjects were summarized according to treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| T-DXd 5.4 mg/kg Q3W | 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 | 98.8 percentage of participants |
| T-DXd 6.4 mg/kg Q3W | 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 | 100 percentage of participants |
Secondary
Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer
Progression Free Survival (PFS) defined as the time from date of randomization/registration until first objective radiographic tumor progression or death from any cause, based on BICR and Investigator assessment according to RECIST version 1.1. PFS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From randomization to data cut off, up to approximately 19 months.
Population: PFS was assessed in the Full Analysis Set, which included 1 participant who was randomized/registered to T-DXd 6.4 mg/kg Q3W but actually received T-DXd 5.4 mg/kg Q3W.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | BICR | 5.8 month |
| T-DXd 5.4 mg/kg Q3W | Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | Investigator | 5.8 month |
| T-DXd 6.4 mg/kg Q3W | Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | BICR | 5.5 month |
| T-DXd 6.4 mg/kg Q3W | Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer | Investigator | 5.7 month |
Secondary
Serum Concentration of Active Metabolite MAAA-1181a
Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)
Population: The PK Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of T-DXd and had measurable serum concentrations of T-DXd. Subjects were analyzed according to the treatment received
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C2D1 - End of Infusion | 1474.48 pg/mL | Geometric Coefficient of Variation 71.2 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D8 - 7 Days After Infusion | 1372.33 pg/mL | Geometric Coefficient of Variation 75.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C3D1 - Before Infusion | 279.56 pg/mL | Geometric Coefficient of Variation 64 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D1 - Before Infusion | NA pg/mL | — |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C3D1 - End of Infusion | 1559.93 pg/mL | Geometric Coefficient of Variation 52.6 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D15 - 14 Days After Infusion | 475.30 pg/mL | Geometric Coefficient of Variation 62.4 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C4D1 - Before Infusion | 284.38 pg/mL | Geometric Coefficient of Variation 81.4 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D1 - 5Hrs After Infusion | 12063.71 pg/mL | Geometric Coefficient of Variation 52.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C4D1 - End of Infusion | 1448.53 pg/mL | Geometric Coefficient of Variation 48.5 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C2D1 - Before Infusion | 209.06 pg/mL | Geometric Coefficient of Variation 74.6 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C6D1 - Before Infusion | 332.07 pg/mL | Geometric Coefficient of Variation 81.3 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C6D1 - End of Infusion | 1182.53 pg/mL | Geometric Coefficient of Variation 36.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D1 - End of Infusion | 4101.40 pg/mL | Geometric Coefficient of Variation 56.6 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C6D1 - End of Infusion | 1512.25 pg/mL | Geometric Coefficient of Variation 32.3 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D1 - Before Infusion | NA pg/mL | — |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D1 - End of Infusion | 4313.38 pg/mL | Geometric Coefficient of Variation 45.3 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D1 - 5Hrs After Infusion | 15773.44 pg/mL | Geometric Coefficient of Variation 39 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D8 - 7 Days After Infusion | 1761.02 pg/mL | Geometric Coefficient of Variation 67.1 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C1D15 - 14 Days After Infusion | 602.43 pg/mL | Geometric Coefficient of Variation 54.1 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C2D1 - Before Infusion | 291.07 pg/mL | Geometric Coefficient of Variation 55.4 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C2D1 - End of Infusion | 1649.91 pg/mL | Geometric Coefficient of Variation 65.8 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C3D1 - Before Infusion | 427.33 pg/mL | Geometric Coefficient of Variation 89.5 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C3D1 - End of Infusion | 1647.92 pg/mL | Geometric Coefficient of Variation 53.1 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C4D1 - Before Infusion | 494.17 pg/mL | Geometric Coefficient of Variation 61.2 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C4D1 - End of Infusion | 1404.67 pg/mL | Geometric Coefficient of Variation 54.1 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Active Metabolite MAAA-1181a | C6D1 - Before Infusion | 578.72 pg/mL | Geometric Coefficient of Variation 55.8 |
Secondary
Serum Concentration of T-DXd
Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)
Population: The PK Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of T-DXd and had measurable serum concentrations of T-DXd. Subjects were analyzed according to the treatment received
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D1 - End of Infusion | 118452.77 ug/L | Geometric Coefficient of Variation 27.5 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C3D1 - Before Infusion | 4823.41 ug/L | Geometric Coefficient of Variation 83.6 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D15 - 14 Days After Infusion | 8092.08 ug/L | Geometric Coefficient of Variation 61.7 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C3D1 - End of Infusion | 122218.96 ug/L | Geometric Coefficient of Variation 25.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D1 - Before Infusion | NA ug/L | — |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C4D1 - Before Infusion | 5846.34 ug/L | Geometric Coefficient of Variation 89.5 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C2D1 - Before Infusion | 2827.01 ug/L | Geometric Coefficient of Variation 118.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C4D1 - End of Infusion | 124240.37 ug/L | Geometric Coefficient of Variation 23.4 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D8 - 7 Days After Infusion | 22261.67 ug/L | Geometric Coefficient of Variation 38.9 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C6D1 - Before Infusion | 7507.28 ug/L | Geometric Coefficient of Variation 74.5 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C2D1 - End of Infusion | 109777.43 ug/L | Geometric Coefficient of Variation 67.2 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C6D1 - End of Infusion | 117769.64 ug/L | Geometric Coefficient of Variation 25.3 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D1 - 5Hrs After Infusion | 123433.28 ug/L | Geometric Coefficient of Variation 23 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C6D1 - End of Infusion | 35753.88 ug/L | Geometric Coefficient of Variation 1079.6 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D1 - 5Hrs After Infusion | 142399.71 ug/L | Geometric Coefficient of Variation 19.8 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D1 - Before Infusion | NA ug/L | — |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D1 - End of Infusion | 134613.79 ug/L | Geometric Coefficient of Variation 18.1 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D8 - 7 Days After Infusion | 28142.80 ug/L | Geometric Coefficient of Variation 51.5 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C1D15 - 14 Days After Infusion | 11396.97 ug/L | Geometric Coefficient of Variation 60.3 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C2D1 - Before Infusion | 4420.63 ug/L | Geometric Coefficient of Variation 73 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C2D1 - End of Infusion | 135637.46 ug/L | Geometric Coefficient of Variation 22.2 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C3D1 - Before Infusion | 7543.17 ug/L | Geometric Coefficient of Variation 74.3 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C3D1 - End of Infusion | 139264.52 ug/L | Geometric Coefficient of Variation 24.7 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C4D1 - Before Infusion | 11013.81 ug/L | Geometric Coefficient of Variation 51.8 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C4D1 - End of Infusion | 134129.68 ug/L | Geometric Coefficient of Variation 30.3 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of T-DXd | C6D1 - Before Infusion | 10793.89 ug/L | Geometric Coefficient of Variation 59 |
Secondary
Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody
Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI)
Population: The PK Analysis Set included all subjects randomized/registered in Stage 1 and/or Stage 2 who received at least 1 dose of T-DXd and had measurable serum concentrations of T-DXd. Subjects were analyzed according to the treatment received
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 - 5Hrs After Infusion | 107339.74 ug/L | Geometric Coefficient of Variation 23.4 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C3D1 - Before Infusion | 6286.00 ug/L | Geometric Coefficient of Variation 93.2 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D15 - 14 Days After Infusion | 10920.88 ug/L | Geometric Coefficient of Variation 71.7 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C3D1 - End of Infusion | 114763.30 ug/L | Geometric Coefficient of Variation 22.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 - Before Infusion | 5211.18 ug/L | Geometric Coefficient of Variation 388.5 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C4D1 - Before Infusion | 7388.01 ug/L | Geometric Coefficient of Variation 101.8 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C2D1 - Before Infusion | 3723.58 ug/L | Geometric Coefficient of Variation 123.1 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C4D1 - End of Infusion | 113711.08 ug/L | Geometric Coefficient of Variation 21.5 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D8 - 7 Days After Infusion | 27646.77 ug/L | Geometric Coefficient of Variation 40.3 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C6D1 - Before Infusion | 9033.08 ug/L | Geometric Coefficient of Variation 94.9 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C2D1 - End of Infusion | 106755.21 ug/L | Geometric Coefficient of Variation 66 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C6D1 - End of Infusion | 104328.76 ug/L | Geometric Coefficient of Variation 35.4 |
| T-DXd 5.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 - End of Infusion | 110871.93 ug/L | Geometric Coefficient of Variation 28.8 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C6D1 - End of Infusion | 37091.52 ug/L | Geometric Coefficient of Variation 816.2 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 - Before Infusion | 11934.79 ug/L | Geometric Coefficient of Variation 2058.9 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 - End of Infusion | 121423.37 ug/L | Geometric Coefficient of Variation 20.3 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D1 - 5Hrs After Infusion | 124274.05 ug/L | Geometric Coefficient of Variation 23 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D8 - 7 Days After Infusion | 32741.77 ug/L | Geometric Coefficient of Variation 49.9 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C1D15 - 14 Days After Infusion | 14293.10 ug/L | Geometric Coefficient of Variation 63 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C2D1 - Before Infusion | 4841.90 ug/L | Geometric Coefficient of Variation 107.5 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C2D1 - End of Infusion | 127427.43 ug/L | Geometric Coefficient of Variation 23.2 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C3D1 - Before Infusion | 9100.39 ug/L | Geometric Coefficient of Variation 90 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C3D1 - End of Infusion | 134111.33 ug/L | Geometric Coefficient of Variation 19.5 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C4D1 - Before Infusion | 14007.95 ug/L | Geometric Coefficient of Variation 67.2 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C4D1 - End of Infusion | 133956.61 ug/L | Geometric Coefficient of Variation 30.5 |
| T-DXd 6.4 mg/kg Q3W | Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody | C6D1 - Before Infusion | 13535.33 ug/L | Geometric Coefficient of Variation 73.5 |
Other Pre-specified
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)
Exploratory outcome, results not included in this submission. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items and no item occurs in more than 1 scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Patient questionnaires were assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.
Time frame: From baseline to data cut off, up to approximately 19 months.
Population: Exploratory outcome, results not included in this submission
Other Pre-specified
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)
Exploratory outcome, results not included in this submission. EORTC QLQ-CR29 is designed to be administered in addition to EORTC QLQ-C30. The EORTC QLQ-CR29 is a specific questionnaire for Colorectal Cancer. Scale from 0 to 100, A higher scale represents better function and a higher quality of life.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: Exploratory outcome, results not included in this submission
Other Pre-specified
Inpatient Healthcare Resource Utilization
Exploratory outcome, results not included in this submission. The impact of treatment and disease on healthcare resource use (including inpatient admissions, intensive care unit admissions, and length of stay in hospital) will be captured/collected in this study on an event-driven basis.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: Exploratory outcome, results not included in this submission
Other Pre-specified
Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIC)
Exploratory outcome, results not included in this submission. The PGIC item is included to assess how a patient perceives their overall change in health status since the start of study treatment. This is a single-item questionnaire, and patients will choose from response options ranging from Much Better to Much Worse.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: Exploratory outcome, results not included in this submission
Other Pre-specified
Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS)
Exploratory outcome, results not included in this submission. The PGIS item is included to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. This is a single-item questionnaire, and patients will choose the response that best describes the severity of their overall cancer symptoms with options ranging from No Symptoms to Very Severe.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: Exploratory outcome, results not included in this submission
Other Pre-specified
Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT)
Exploratory outcome, results not included in this submission. The PGI-TT item is included to assess how a patient perceives the overall tolerability of the study treatment over the past 7 days. This is a single-item questionnaire, and patients will rate the bother associated with any treatment-related symptoms using response options ranging from Not at all to Very much.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: Exploratory outcome, results not included in this submission
Other Pre-specified
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)
Exploratory outcome, results not included in this submission. The EQ-5D-5L is self-administered and consists of 2 parts, the EQ-5D-5L descriptive system and the EQ-visual analogue scale. On each dimension, a score of 1 indicates no patient problems in that dimension, 2 indicates slight problems in that dimension, 3 indicates moderate problems in that dimension, 4 indicates severe problems in that dimension and 5 indicates extreme problems in that dimension.
Time frame: From baseline to data cut off, up to approximately 19 months
Population: Exploratory outcome, results not included in this submission