A Phase 2 interventional study of DS-8201a in Colorectal Neoplasm, sponsored by Daiichi Sankyo Co., Ltd.. Completed at 25 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-18.
Sponsored by Daiichi Sankyo Co., Ltd. · Phase 2, Interventional, and Treatment
The main objective of this study is to test the safety and effectiveness of DS-8201a for participants with HER2-expressing advanced colorectal cancer.
At study start, only Cohort A is active.
If, and when, Cohort B and C become active depends on the assessment of benefit and risk observed in the program.
The sponsor will inform the investigators if, and when, Cohort B and C are active.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's enrollment of 86 is above the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Daiichi Sankyo Co., Ltd. is the lead sponsor of 73 studies on the registry; none are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 8 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks
Drug: DS-8201a
Cohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks
Drug: DS-8201a
Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks
Drug: DS-8201a
DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration
Also known as: Trastuzumab deruxtecan
Number of Participants With Best Objective Response Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Best objective response was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
Number of Participants With Objective Response Rate Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Objective response rate (defined as CR+PR) was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a 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: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
Number of Participants With Best Objective Response Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Best objective response was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
Number of Participants With Objective Response Rate Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Objective response rate (defined as CR+PR) was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a 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: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
Duration of Response (Confirmed and Unconfirmed) Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Duration of response (DoR) is defined as the time from the date of the first documentation of an objective response (CR\[disappearance of all target lesions\] or PR \[at least a 30% decrease in the sum of diameters of target lesions\]) to the date of the first documentation of PD (at least a 20% increase in the sum of diameters of target lesions). Duration of response was measured for responding participants (CR or PR) only. Month was calculated as (duration of response days × 12)/365.25 for duration of response and calculated as (time to response days × 12)/365.25 for time to response.
Time frame: Date of first documentation of objective response (CR or PR) up to date of first documentation of PD, up to approximately 18 months post-dose
Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Disease control rate (DCR) was defined as the proportion of participants who achieved a best overall response of CR + PR + SD based on independent central review and investigator assessment. As per RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions).
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
Progression-Free Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
Progression-Free Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.Point estimates at 3, 6, 9, and 12 months are based on Kaplan-Meier estimate. CI is computed using the Brookmeyer-Crowley method. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.
Time frame: Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
Overall Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
Time frame: Time from the date of first dose to date of death from any cause, up to approximately 18 months
Overall Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.
Time frame: Time from the date of first dose to date of death from any cause, up to approximately 18 months
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
Time frame: Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Maximum serum concentration (Cmax) of MAAA-1181a was assessed.
Time frame: Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.
Time frame: Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of DS-8201a and total anti-HER2 antibody were assessed.
Time frame: Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) of MAAA-1181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.
Time frame: Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.
Time frame: From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months
A total of 86 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at clinic centers in Japan, United States, Spain, and Italy.
| Milestone | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Started | 53 | 15 | 18 |
| Completed | 0 | 0 | 0 |
| Not completed | 53 | 15 | 18 |
| Withdrew: Progressive disease | 36 | 11 | 13 |
| Withdrew: Clinical progression | 4 | 0 | 3 |
| Withdrew: Adverse event | 7 | 1 | 1 |
| Withdrew: Withdrawal by subject | 3 | 1 | 0 |
| Withdrew: Physician decision | 1 | 1 | 0 |
| Withdrew: Death | 2 | 1 | 0 |
| Withdrew: Other | 0 | 0 | 1 |
Best objective response was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
| Participants | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Confirmed CR | 0 | 0 | 0 |
| Confirmed PR | 24 | 0 | 0 |
| Confirmed SD | 20 | 9 | 4 |
| Confirmed PD | 5 | 5 | 10 |
| Confirmed Non-evaluable | 4 | 1 | 4 |
| Unconfirmed CR | 0 | 0 | 0 |
| Unconfirmed PR | 26 | 0 | 0 |
| Unconfirmed SD | 18 | 9 | 4 |
| Unconfirmed PD | 5 | 5 | 10 |
| Unconfirmed Non-evaluable | 4 | 1 | 4 |
Objective response rate (defined as CR+PR) was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
| Participants | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Confirmed CR+PR | 24 | 0 | 0 |
| Confirmed CR+PR (within 3 months) | 10 | 0 | 0 |
| Confirmed CR+PR (within 6 months) | 23 | 0 | 0 |
| Confirmed CR+PR (within 9 months) | 24 | 0 | 0 |
| Confirmed CR+PR (12 months) | 24 | 0 | 0 |
| Unconfirmed CR+PR | 26 | 0 | 0 |
| Unconfirmed CR+PR (within 3 months) | 20 | 0 | 0 |
| Unconfirmed CR+PR (within 6 months) | 25 | 0 | 0 |
| Unconfirmed CR+PR (within 9 months) | 25 | 0 | 0 |
| Unconfirmed CR+PR (within 12 months) | 25 | 0 | 0 |
Best objective response was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
| Participants | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Confirmed CR | 0 | 0 | 0 |
| Confirmed PR | 25 | 0 | 0 |
| Confirmed SD | 18 | 7 | 6 |
| Confirmed PD | 6 | 7 | 8 |
| Confirmed Non-evaluable | 4 | 1 | 4 |
| Unconfirmed CR | 0 | 0 | 0 |
| Unconfirmed PR | 28 | 0 | 0 |
| Unconfirmed SD | 15 | 7 | 6 |
| Unconfirmed PD | 6 | 7 | 8 |
| Unconfirmed Non-evaluable | 4 | 1 | 4 |
Objective response rate (defined as CR+PR) was reported based on investigator. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
| Participants | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Confirmed CR+PR | 25 | 0 | 0 |
| Unconfirmed CR+PR | 28 | 0 | 0 |
Duration of response (DoR) is defined as the time from the date of the first documentation of an objective response (CR\[disappearance of all target lesions\] or PR \[at least a 30% decrease in the sum of diameters of target lesions\]) to the date of the first documentation of PD (at least a 20% increase in the sum of diameters of target lesions). Duration of response was measured for responding participants (CR or PR) only. Month was calculated as (duration of response days × 12)/365.25 for duration of response and calculated as (time to response days × 12)/365.25 for time to response.
| months | DS-8201a Cohort A |
|---|---|
| Confirmed DoR | 7.0 (5.8 to 9.5) |
| Unconfirmed DoR | 7.0 (5.8 to 9.5) |
Disease control rate (DCR) was defined as the proportion of participants who achieved a best overall response of CR + PR + SD based on independent central review and investigator assessment. As per RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions).
| Participants | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Confirmed CR+PR+SD (Independent Central Review) | 44 | 9 | 4 |
| Unconfirmed CR+PR+SD (Independent Central Review) | 44 | 9 | 4 |
| Confirmed CR+PR+SD (Investigator) | 43 | 7 | 6 |
| Unconfirmed CR+PR+SD (Investigator) | 43 | 7 | 6 |
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
| months | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Progression-Free Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer | 6.9 (4.1 to 8.7) | 2.1 (1.4 to 4.1) | 1.4 (1.3 to 2.1) |
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.Point estimates at 3, 6, 9, and 12 months are based on Kaplan-Meier estimate. CI is computed using the Brookmeyer-Crowley method. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.
| point estimate percentage | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Progression-free survival at 3 months | 74.4 (60.0 to 84.3) | 38.3 (13.0 to 63.6) | 7.5 (0.5 to 28.3) |
| Progression-free survival at 6 months | 55 (40.0 to 67.8) | 0 (NA to NA) | 0 (NA to NA) |
| Progression-free survival at 9 months | 34.1 (19.7 to 49.1) | 0 (NA to NA) | 0 (NA to NA) |
| Progression-free survival at 12 months | 19.0 (7.5 to 34.3) | 0 (NA to NA) | 0 (NA to NA) |
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
| months | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Overall Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer | 15.5 (8.8 to 20.8) | 7.3 (3.0 to NA) | 7.7 (2.2 to 13.9) |
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.
| point estimate percentage | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Overall survival at 3 months | 86.8 (74.3 to 93.5) | 86.7 (56.4 to 96.5) | 77.0 (49.7 to 90.7) |
| Overall survival at 6 months | 73.6 (59.5 to 83.4) | 53.3 (26.3 to 74.4) | 57.8 (31.0 to 77.3) |
| Overall survival at 9 months | 62.0 (47.5 to 73.5) | 38.1 (14.6 to 61.6) | 43.3 (18.9 to 65.7) |
| Overall survival at 12 months | 60.0 (45.5 to 71.8) | 38.1 (14.6 to 61.6) | 28.9 (9.3 to 52.3) |
Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
| ug/mL | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| DS-8201a | 135 ± 32.7 | 123 ± 29.5 | 122 ± 41.5 |
| Total anti-HER2 antibody | 130 ± 35.1 | 106 ± 24.6 | 109 ± 35.4 |
Maximum serum concentration (Cmax) of MAAA-1181a was assessed.
| ng/mL | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer | 15.8 ± 7.67 | 12.9 ± 6.40 | 15.1 ± 5.30 |
Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.
| hours | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| DS-8201a | 1.95 (1.42 to 8.75) | 1.72 (1.25 to 5.08) | 3.00 (0.88 to 6.92) |
| Total anti-HER2 antibody | 1.72 (1.42 to 6.95) | 1.68 (1.25 to 7.08) | 1.93 (0.88 to 6.92) |
| MAAA-1181a | 5.17 (1.75 to 8.75) | 5.00 (3.83 to 6.97) | 5.25 (3.83 to 7.00) |
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of DS-8201a and total anti-HER2 antibody were assessed.
| ug*d/mL | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| DS-8201a: AUC21d | 610 ± 198 | 571 ± 208 | 577 ± 219 |
| DS-8201a: AUClast | 600 ± 204 | 559 ± 211 | 577 ± 237 |
| Total anti-HER2 antibody: AUC21d | 661 ± 218 | 569 ± 224 | 574 ± 219 |
| Total anti-HER2 antibody: AUClast | 638 ± 235 | 558 ± 225 | 555 ± 224 |
Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.
| ng*d/mL | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| MAAA-1181a: AUC21d | 60.2 ± 42.7 | 45.0 ± 28.1 | 55.1 ± 19.6 |
| MAAA-1181a: AUClast | 59.5 ± 42.1 | 47.1 ± 29.4 | 62.5 ± 19.6 |
A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.
| Participants | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Any TEAE | 53 | 15 | 18 |
| Nausea | 37 | 9 | 7 |
| Anaemia | 21 | 4 | 6 |
| Decreased appetite | 18 | 5 | 7 |
| Fatigue | 21 | 7 | 3 |
| Neutrophil count decreased | 20 | 2 | 4 |
| Platelet count decreased | 17 | 4 | 7 |
| Vomiting | 23 | 3 | 1 |
| Diarrhoea | 19 | 0 | 4 |
| Alopecia | 12 | 4 | 1 |
| Constipation | 10 | 3 | 1 |
| Hypokalaemia | 9 | 1 | 4 |
| Aspartate aminotransferase increased | 6 | 1 | 4 |
| Malaise | 5 | 0 | 4 |
| Interstitial lung disease | 4 | 3 | 1 |
| Dyspnoea | 3 | 3 | 0 |
Collected over Adverse events were collected from the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| DS-8201a Cohort A | 36/53 (67.9%) | 20/53 (37.7%) | 53/53 (100%) |
| DS-8201a Cohort B | 10/15 (66.7%) | 6/15 (40%) | 15/15 (100%) |
| DS-8201a Cohort C | 12/18 (66.7%) | 9/18 (50%) | 18/18 (100%) |
| Event | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 1/53 | 2/15 | 1/18 |
| NauseaGastrointestinal disorders | 2/53 | 1/15 | 0/18 |
| Acute kidney injuryRenal and urinary disorders | 0/53 | 1/15 | 1/18 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/53 | 1/15 | 0/18 |
| Intestinal obstructionGastrointestinal disorders | 0/53 | 1/15 | 0/18 |
| Small intestinal obstructionGastrointestinal disorders | 0/53 | 1/15 | 0/18 |
| Bile duct obstructionHepatobiliary disorders | 0/53 | 1/15 | 0/18 |
| SepsisInfections and infestations | 3/53 | 0/15 | 1/18 |
| Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/53 | 0/15 | 1/18 |
| DiarrhoeaGastrointestinal disorders | 2/53 | 0/15 | 1/18 |
| Event | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C |
|---|---|---|---|
| NauseaGastrointestinal disorders | 37/53 | 9/15 | 7/18 |
| FatigueGeneral disorders | 21/53 | 7/15 | 3/18 |
| VomitingGastrointestinal disorders | 23/53 | 3/15 | 1/18 |
| AnaemiaBlood and lymphatic system disorders | 21/53 | 4/15 | 6/18 |
| Decreased appetiteMetabolism and nutrition disorders | 18/53 | 5/15 | 7/18 |
| Platelet count decreasedInvestigations | 17/53 | 4/15 | 7/18 |
| Neutrophil count decreasedInvestigations | 20/53 | 2/15 | 4/18 |
| DiarrhoeaGastrointestinal disorders | 19/53 | 0/15 | 4/18 |
| AlopeciaSkin and subcutaneous tissue disorders | 12/53 | 4/15 | 1/18 |
| HypokalaemiaMetabolism and nutrition disorders | 9/53 | 1/15 | 4/18 |
The baseline demographic characteristics were derived from the Full Analysis Set.
| Age, Categorical(Participants) | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 35 | 8 | 13 | 56 |
| >=65 years | 18 | 7 | 5 | 30 |
| Age, Continuous(years) | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | Total |
|---|---|---|---|---|
| Mean | 57.5 ± 11.72 | 61.5 ± 11.95 | 58.5 ± 9.97 | 58.4 ± 11.38 |
| Sex: Female, Male(Participants) | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | Total |
|---|---|---|---|---|
| Female | 28 | 5 | 7 | 40 |
| Male | 25 | 10 | 11 | 46 |
| Race (NIH/OMB)(Participants) | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 16 | 3 | 8 | 27 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 34 | 11 | 8 | 53 |
| More than one race | 1 | 0 | 1 | 2 |
| Unknown or Not Reported | 2 | 1 | 1 | 4 |
| Region of Enrollment(participants) | DS-8201a Cohort A | DS-8201a Cohort B | DS-8201a Cohort C | Total |
|---|---|---|---|---|
| United States | 10 | 3 | 1 | 14 |
| Japan | 15 | 3 | 8 | 26 |
| Italy | 26 | 7 | 8 | 41 |
| Spain | 2 | 1 | 1 | 4 |
| United Kingdom | 0 | 1 | 0 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — 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 information: Study protocol, Statistical analysis plan, Clinical study report
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.
Data sharing details ↗ · vivli.org
This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Trastuzumab deruxtecan