A Phase 2 interventional study of DS-8201a and Physician's Choice in Neoplasm, Gastrointestinal, sponsored by Daiichi Sankyo Co., Ltd.. Completed at 66 sites in 2 countries. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2022-03-18.
Sponsored by Daiichi Sankyo Co., Ltd. · Phase 2, Interventional, and Treatment
The primary purpose of this trial is to compare the efficacy and safety of DS-8201a and physician's choice treatment in HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma patients who have progressed on two prior treatment regimens including fluoropyrimidine agent, platinum agent, and trastuzumab.
695 studies on the registry are indexed under Gastrointestinal Neoplasms; 209 are open to participants now.
This study's enrollment of 233 is above the median of 74 across 494 interventional studies indexed under Gastrointestinal Neoplasms.
Browse Gastrointestinal 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:
Has history of any disease, condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
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.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
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.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
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.
Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive DS-8201a once every 3 weeks.
Drug: DS-8201a
Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive monotherapy prescribed by the physician before enrollment.
Drug: Physician's Choice
A maximum of 20 non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every three weeks.
Drug: DS-8201a
A maximum of 20 non-randomized patients with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma 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: Experimental product
Either: Irinotecan monotherapy (Starting dosage and usage is 150 mg/m2 biweekly, with dose reduction permitted) Paclitaxel monotherapy (Starting dosage and usage is 80 mg/m2 weekly, with dose reduction permitted)
Also known as: Standard of Care
Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) based on 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. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported.
Time frame: Baseline to date of first documented objective response (CR or PR), up to 36 months postdose
Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on 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 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. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported.
Time frame: Baseline to date of first documented objective response, up to 36 months postdose
Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.
Time frame: From the date of randomization to the date of death (due to any cause), up to 36 months postdose
Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) 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: From the date of randomization to the first documented disease progression or date of death (whichever occurs first), up to 36 months postdose
Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only.
Time frame: From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 36 months postdose
Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. 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 to date of first documented objective response (CR, PR, and SD), up to 36 months postdose
Objective Response Rate and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Independent Central Review (ICR) based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.
Time frame: From randomization to first documented objective response, up to 36 months postdose
Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.
Time frame: From date of randomization to first documentation of PD, death due to any cause, or treatment discontinuation (whichever comes first), up to 36 months postdose
Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set)
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.
Time frame: From randomization to first documented objective response, up to 36 months postdose
Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
Time frame: Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time frame: Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
Time frame: Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time frame: Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time frame: Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time frame: Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set)
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.
Time frame: Baseline up to 47 days after last dose, up to 36 months postdose
Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) ≥20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set)
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
Time frame: Baseline up to 47 days after last dose, up to 36 months postdose
In the Primary Cohort, a total of 188 participants who met all inclusion criteria and no exclusion criteria were enrolled and randomized to treatment. In the Exploratory Cohorts, a total of 45 non-randomized participants were enrolled and 44 patients received treatment. Study participants for all cohorts were enrolled at clinic sites in South Korea and Japan. Participants took part of the study from November 2, 2017 to Data Cut-Off (DCO) date of December 11, 2020.
| Milestone | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|
| Started | 126 | 55 | 7 | 21 | 24 |
| Received treatment | 125 | 55 | 7 | 20 | 24 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 126 | 55 | 7 | 21 | 24 |
| Withdrew: Progressive disease per recist | 85 | 44 | 6 | 16 | 20 |
| Withdrew: Clinical progression | 7 | 4 | 1 | 1 | 1 |
| Withdrew: Adverse event | 22 | 4 | 0 | 1 | 2 |
| Withdrew: Death | 2 | 0 | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 2 | 3 | 0 | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 | 0 | 0 | 1 |
| Withdrew: Miscellaneous | 6 | 0 | 0 | 0 | 0 |
| Withdrew: Did not receive treatment | 1 | 0 | 0 | 1 | 0 |
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) based on 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. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported.
| Participants | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall |
|---|---|---|---|---|
| Unconfirmed ORR, 25 months (DCO: Nov 8, 2019) | 61 | 7 | 1 | 8 |
| Unconfirmed ORR, 36 months (DCO: Dec 11, 2020) | 61 | 7 | 1 | 8 |
| Confirmed ORR, 25 months (DCO: Nov 8, 2019) | 51 | 6 | 1 | 7 |
| Confirmed ORR, 36 months (DCO: Dec 11, 2020) | 50 | 6 | 1 | 7 |
The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on 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 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. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported.
| Participants | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall |
|---|---|---|---|---|
| Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019) | 11 | 0 | 0 | 0 |
| Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020) | 10 | 0 | 0 | 0 |
| Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019) | 50 | 7 | 1 | 8 |
| Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020) | 51 | 7 | 1 | 8 |
| Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019) | 46 | 27 | 3 | 30 |
| Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020) | 47 | 27 | 3 | 30 |
| Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019) | 15 | 18 | 0 | 18 |
| Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020) | 15 | 18 | 0 | 18 |
| Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019) | 4 | 3 | 3 | 6 |
| Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020) | 3 | 3 | 3 | 6 |
| Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019) | 10 | 0 | 0 | 0 |
| Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020) | 9 | 0 | 0 | 0 |
| Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019) | 41 | 6 | 1 | 7 |
| Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020) | 41 | 6 | 1 | 7 |
| Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019) | 55 | 28 | 3 | 31 |
| Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020) | 57 | 28 | 3 | 31 |
| Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019) | 15 | 18 | 0 | 18 |
| Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020) | 15 | 18 | 0 | 18 |
| Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019) | 5 | 3 | 3 | 6 |
| Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020) | 4 | 3 | 3 | 6 |
Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.
| months | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| Duration of survival follow up, 25 months (DCO: Nov 8, 2019) | 8.0 (0.4 to 23.1) | 7.1 (0.3 to 20.3) | 5.5 (2.0 to 14.3) | 7.0 (0.3 to 20.3) | 7.3 (0.2 to 19.6) | 8.4 (1.8 to 14.8) |
| Duration of survival follow up, 36 months (DCO: Dec 11, 2020) | 12.3 (0.4 to 33.2) | 8.4 (0.3 to 29.3) | 14.3 (2.0 to 22.1) | 8.5 (0.3 to 29.3) | 7.3 (0.2 to 27.7) | 8.5 (1.8 to 23.1) |
| Overall survival, 25 months (DCO: Nov 8, 2019) | 12.5 (0.4 to 23.1) | 8.4 (0.3 to 20.3) | 14.3 (2.0 to 14.3) | 8.4 (0.3 to 20.3) | 7.8 (0.2 to 19.6) | 8.5 (1.8 to 14.8) |
| Overall survival, 36 months (DCO: Dec 11, 2020) | 12.6 (0.4 to 33.2) | 8.6 (0.3 to 29.3) | 14.3 (2.0 to 22.1) | 8.9 (0.3 to 29.3) | 7.8 (0.2 to 27.7) | 8.5 (1.8 to 23.1) |
Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) 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 | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| PFS, 25 months (DCO: Nov 8, 2019) | 5.6 (4.3 to 6.9) | 2.8 (2.0 to 4.3) | 4.9 (2.0 to NA) | 3.5 (2.0 to 4.3) | 4.4 (2.7 to 7.1) | 2.8 (1.5 to 4.3) |
| PFS, 36 months (DCO: Dec 11, 2020) | 5.6 (4.3 to 6.9) | 2.8 (2.0 to 4.3) | 4.9 (2.0 to NA) | 3.5 (2.0 to 4.3) | 4.4 (2.7 to 7.1) | 2.8 (1.5 to 4.3) |
Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only.
| months | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| Unconfirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019) | 8.4 (0 to 21.0) | 4.1 (0 to 4.9) | 3.9 (3.9 to 3.9) | 3.9 (0 to 4.9) | 6.8 (1.4 to 9.7) | 7.1 (1.4 to 12.5) |
| Unconfirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020) | 11.3 (0 to 29.1) | 4.1 (0 to 4.9) | 3.9 (3.9 to 3.9) | 3.9 (0 to 4.9) | 6.8 (1.4 to 12.5) | 5.8 (1.4 to 12.5) |
| Confirmed Duration of response (DOR), 25 months (DCO: Nov 8, 2019) | 11.3 (1.4 to 21.0) | 4.1 (1.4 to 4.9) | 3.9 (3.9 to 3.9) | 3.9 (1.4 to 4.9) | 7.6 (2.4 to 9.7) | 12.5 (8.1 to 12.5) |
| Confirmed Duration of response (DOR), 36 months (DCO: Dec 11, 2020) | 12.7 (1.4 to 29.1) | 4.1 (1.4 to 4.9) | 3.9 (3.9 to 3.9) | 3.9 (1.4 to 4.9) | 7.6 (2.4 to 12.5) | 11.2 (10.0 to 12.5) |
Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. 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 | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| DCR, 25 months (DCO: Nov 8, 2019) | 107 | 34 | 4 | 38 | 17 | 15 |
| DCR, 36 months (DCO: Dec 11, 2020) | 108 | 34 | 4 | 38 | 17 | 15 |
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Independent Central Review (ICR) based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.
| Participants | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|
| Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019) | 5 | 2 |
| Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020) | 5 | 2 |
| Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019) | 0 | 0 |
| Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020) | 0 | 0 |
| Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019) | 5 | 2 |
| Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020) | 5 | 2 |
| Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019) | 12 | 13 |
| Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020) | 12 | 13 |
| Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019) | 3 | 6 |
| Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020) | 3 | 6 |
| Inevaluable, 25 months (DCO: Nov 8, 2019) | 1 | 1 |
| Inevaluable, 36 months (DCO: Dec 11, 2020) | 1 | 1 |
Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.
| months | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| TTF, 25 months (DCO: Nov 8, 2019) | 4.2 (3.9 to 5.1) | 2.6 (1.6 to 2.8) | 2.9 (1.1 to 6.8) | 2.6 (1.6 to 2.8) | 3.7 (1.7 to 5.5) | 2.2 (1.4 to 3.0) |
| TTF, 36 months (DCO: Dec 11, 2020) | 4.3 (3.9 to 5.4) | 2.6 (1.6 to 2.8) | 2.9 (1.1 to 6.8) | 2.6 (1.6 to 2.8) | 3.7 (1.7 to 5.5) | 2.2 (1.4 to 3.0) |
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.
| Participants | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| Unconfirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019) | 60 | 7 | 1 | 8 | 10 | 5 |
| Unconfirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020) | 60 | 7 | 1 | 8 | 10 | 5 |
| Unconfirmed Complete response (CR), 25 months (DCO: Nov 8, 2019) | 4 | 0 | 0 | 0 | 0 | 0 |
| Unconfirmed Complete response (CR), 36 months (DCO: Dec 11, 2020) | 4 | 0 | 0 | 0 | 0 | 0 |
| Unconfirmed Partial response (PR), 25 months (DCO: Nov 8, 2019) | 56 | 7 | 1 | 8 | 10 | 5 |
| Unconfirmed Partial response (PR), 36 months (DCO: Dec 11, 2020) | 56 | 7 | 1 | 8 | 10 | 5 |
| Unconfirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019) | 42 | 27 | 1 | 28 | 7 | 8 |
| Unconfirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020) | 42 | 27 | 1 | 28 | 7 | 8 |
| Unconfirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019) | 15 | 15 | 2 | 17 | 2 | 8 |
| Unconfirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020) | 15 | 15 | 2 | 17 | 2 | 8 |
| Unconfirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019) | 2 | 2 | 1 | 3 | 0 | 0 |
| Unconfirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020) | 2 | 2 | 1 | 3 | 0 | 0 |
| Confirmed Objective response rate (ORR), 25 months (DCO: Nov 8, 2019) | 49 | 5 | 1 | 6 | 8 | 3 |
| Confirmed Objective response rate (ORR), 36 months (DCO: Dec 11, 2020) | 51 | 5 | 1 | 6 | 8 | 3 |
| Confirmed Complete response (CR), 25 months (DCO: Nov 8, 2019) | 3 | 0 | 0 | 0 | 0 | 0 |
| Confirmed Complete response (CR), 36 months (DCO: Dec 11, 2020) | 4 | 0 | 0 | 0 | 0 | 0 |
| Confirmed Partial response (PR), 25 months (DCO: Nov 8, 2019) | 46 | 5 | 1 | 6 | 8 | 3 |
| Confirmed Partial response (PR), 36 months (DCO: Dec 11, 2020) | 47 | 5 | 1 | 6 | 8 | 3 |
| Confirmed Stable disease (SD), 25 months (DCO: Nov 8, 2019) | 53 | 28 | 1 | 29 | 9 | 10 |
| Confirmed Stable disease (SD), 36 months (DCO: Dec 11, 2020) | 51 | 28 | 1 | 29 | 9 | 10 |
| Confirmed Progressive disease (PD), 25 months (DCO: Nov 8, 2019) | 15 | 16 | 2 | 18 | 2 | 8 |
| Confirmed Progressive disease (PD), 36 months (DCO: Dec 11, 2020) | 15 | 16 | 2 | 18 | 2 | 8 |
| Confirmed Not evaluable (NE), 25 months (DCO: Nov 8, 2019) | 2 | 2 | 1 | 3 | 0 | 0 |
| Confirmed Not evaluable (NE), 36 months (DCO: Dec 11, 2020) | 2 | 2 | 1 | 3 | 0 | 0 |
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
| ug/mL | DS-8201a | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|
| Cmax: DS-8201a, Cycle 1 | 127 ± 28.4 | 119 ± 29.1 | 127 ± 24.5 |
| Cmax: DS-8201a, Cycle 3 | 137 ± 31.1 | 128 ± 25.6 | 123 ± 23.2 |
| Cmax: Total Anti-HER2 antibody, Cycle 1 | 116 ± 30.6 | 105 ± 26.1 | 110 ± 19.6 |
| Cmax: Total Anti-HER2 antibody, Cycle 3 | 121 ± 28.4 | 115 ± 24.2 | 112 ± 21.9 |
| Ctrough: DS-8201a, Cycle 1 | 5.56 ± 3.08 | 4.52 ± 2.42 | 9.51 ± 23.4 |
| Ctrough: DS-8201a, Cycle 3 | 13.4 ± 17.3 | 8.84 ± 3.09 | 13.2 ± 18.6 |
| Ctrough: Total Anti-HER2 antibody, Cycle 1 | 8.56 ± 8.60 | 5.33 ± 2.97 | 10.0 ± 20.5 |
| Ctrough: Total Anti-HER2 antibody, Cycle 3 | 15.6 ± 13.6 | 12.2 ± 5.76 | 14.6 ± 17.6 |
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
| ng/mL | DS-8201a | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|
| Cmax: MAAA-1181a, Cycle 1 | 12.1 ± 4.79 | 13.3 ± 8.52 | 13.3 ± 7.37 |
| Cmax: MAAA-1181a, Cycle 3 | 9.08 ± 3.81 | 7.62 ± 1.86 | 9.83 ± 3.75 |
| Ctrough: MAAA-1181a, Cycle 1 | 0.316 ± 0.294 | 0.290 ± 0.237 | 0.772 ± 2.28 |
| Ctrough: MAAA-1181a Cycle 3 | 0.714 ± 2.19 | 0.378 ± 0.138 | 1.10 ± 1.95 |
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
| ug*d/mL | DS-8201a | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|
| AUClast: DS-8201a, Cycle 1 | 611 ± 150 | 572 ± 143 | 545 ± 160 |
| AUClast: Total Anti-HER2 antibody, Cycle 1 | 667 ± 241 | 570 ± 126 | 547 ± 167 |
| AUC21d: DS-8201a, Cycle 1 | 612 ± 150 | 572 ± 143 | 569 ± 114 |
| AUC21d: DS-8201a, Cycle 3 | 867 ± 213 | 746 ± 197 | 724 ± 71.9 |
| AUC21d: Total Anti-HER2 antibody, Cycle 1 | 651 ± 210 | 570 ± 126 | 582 ± 104 |
| AUC21d: Total Anti-HER2 antibody, Cycle 3 | 888 ± 244 | 775 ± 210 | 737 ± 110 |
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
| ng*d/mL | DS-8201a | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|
| AUClast: MAAA-1181a, Cycle 1 | 46.7 ± 16.3 | 53.4 ± 42.7 | 44.5 ± 22.5 |
| AUC21d: MAAA-1181a, Cycle 1 | 46.4 ± 16.1 | 44.9 ± 20.1 | 44.5 ± 22.5 |
| AUC21d: MAAA-1181a, Cycle 3 | 42.0 ± 15.1 | 39.4 ± 8.36 | 44.6 ± 17.8 |
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
| hours | DS-8201a | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|
| DS-8201a, Cycle 1 | 3.93 (0 to 7.15) | 3.90 (1.58 to 7.12) | 3.89 (1.53 to 7.08) |
| DS-8201a, Cycle 3 | 4.00 (0.58 to 7.25) | 4.00 (0.58 to 6.82) | 4.00 (0.68 to 7.02) |
| Total Anti-HER2 antibody, Cycle 1 | 3.83 (0 to 7.15) | 3.83 (1.58 to 7.08) | 3.87 (1.53 to 7.08) |
| Total Anti-HER2 antibody, Cycle 3 | 3.98 (0.53 to 7.17) | 4.00 (0.57 to 6.83) | 3.75 (0.53 to 7.03) |
| MAAA-1181a, Cycle 1 | 6.85 (3.75 to 7.25) | 6.83 (3.83 to 141.73) | 6.81 (3.83 to 7.08) |
| MAAA-1181a, Cycle 3 | 6.80 (3.78 to 7.25) | 6.82 (3.88 to 7.10) | 6.77 (3.98 to 7.07) |
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
| days | DS-8201a | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|
| DS-8201a, Cycle 1 | 5.77 ± 1.37 | 5.54 ± 1.08 | 5.52 ± 1.17 |
| DS-8201a, Cycle 3 | 7.46 ± 1.82 | 6.40 ± 1.00 | 6.35 ± 1.73 |
| Total Anti-HER2 antibody, Cycle 1 | 6.20 ± 2.22 | 5.54 ± 1.01 | 5.65 ± 1.51 |
| Total Anti-HER2 antibody, Cycle 3 | 8.00 ± 2.04 | 7.90 ± 2.10 | 6.17 ± 1.15 |
| MAAA-1181a, Cycle 1 | 5.50 ± 1.11 | 5.21 ± 0.939 | 5.61 ± 1.19 |
| MAAA-1181a, Cycle 3 | 7.01 ± 1.65 | 6.18 ± 1.02 | 5.80 ± 1.10 |
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.
| Participants | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| Any TEAE, 25 months (DCO: Nov 8, 2019) | 125 | 54 | 7 | 61 | 20 | 24 |
| Any TEAE, 36 months (DCO: Dec 11, 2020) | 125 | 54 | 7 | 61 | 20 | 24 |
| Drug-related TEAEs, 25 months (DCO: Nov 8, 2019) | 122 | 51 | 5 | 56 | 19 | 24 |
| Drug-related TEAEs, 36 months (DCO: Dec 11, 2020) | 122 | 51 | 5 | 56 | 19 | 24 |
| Serious TEAEs, 25 months (DCO: Nov 8, 2019) | 55 | 14 | 1 | 15 | 6 | 11 |
| Serious TEAEs, 36 months (DCO: Dec 11, 2020) | 58 | 15 | 1 | 16 | 6 | 11 |
| Drug-related serious TEAEs, 25 months (DCO: Nov 8, 2019) | 27 | 5 | 0 | 5 | 1 | 6 |
| Drug-related serious TEAEs, 36 months (DCO: Dec 11, 2020) | 31 | 5 | 0 | 5 | 1 | 6 |
| TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019) | 19 | 4 | 0 | 4 | 2 | 1 |
| TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020) | 23 | 4 | 0 | 4 | 2 | 1 |
| Drug-related TEAEs associated with drug withdrawn, 25 months (DCO: Nov 8, 2019) | 12 | 3 | 0 | 3 | 1 | 0 |
| Drug-related TEAEs associated with drug withdrawn, 36 months (DCO: Dec 11, 2020) | 15 | 3 | 0 | 3 | 1 | 0 |
| TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019) | 40 | 21 | 0 | 21 | 6 | 8 |
| TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020) | 40 | 21 | 0 | 21 | 6 | 8 |
| Drug-related TEAEs associated with dose reduced, 25 months (DCO: Nov 8, 2019) | 38 | 21 | 0 | 21 | 6 | 7 |
| Drug-related TEAEs associated with dose reduced, 36 months (DCO: Dec 11, 2020) | 38 | 21 | 0 | 21 | 6 | 7 |
| TEAEs associated with drug interrupted, 25 months (DCO: Nov 8, 2019) | 78 | 20 | 3 | 23 | 8 | 10 |
| TEAEs associated with drug interrupted, 36 months (DCO: Dec 11, 2020) | 79 | 20 | 3 | 23 | 8 | 10 |
| Drug-related TEAE associated with drug interrupted, 25 months (DCO: Nov 8, 2019) | 64 | 17 | 2 | 19 | 7 | 10 |
| Drug-related TEAE associated with drug interrupted, 36 months (DCO: Dec 11, 2020) | 65 | 17 | 2 | 19 | 7 | 10 |
| TEAEs associated with death, 25 months (DCO: Nov 8, 2019) | 8 | 1 | 1 | 2 | 2 | 0 |
| TEAEs associated with death, 36 months (DCO: Dec 11, 2020) | 9 | 1 | 1 | 2 | 2 | 0 |
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
| Participants | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| Any TEAE, 25 months (DCO: Nov 8, 2019) | 125 | 54 | 7 | 61 | 20 | 24 |
| Any TEAE, 36 months (DCO: Dec 11, 2020) | 125 | 54 | 7 | 61 | 20 | 24 |
| Nausea, 25 months (DCO: Nov 8, 2019) | 79 | 27 | 2 | 29 | 11 | 19 |
| Nausea, 36 months (DCO: Dec 11, 2020) | 79 | 27 | 2 | 29 | 11 | 19 |
| Decreased appetite, 25 months (DCO: Nov 8, 2019) | 75 | 27 | 1 | 28 | 13 | 18 |
| Decreased appetite, 36 months (DCO: Dec 11, 2020) | 76 | 27 | 1 | 28 | 13 | 18 |
| Neutrophil count decreased, 25 months (DCO: Nov 8, 2019) | 77 | 18 | 3 | 21 | 8 | 12 |
| Neutrophil count decreased, 36 months (DCO: Dec 11, 2020) | 79 | 18 | 3 | 21 | 8 | 12 |
| Anaemia, 25 months (DCO: Nov 8, 2019) | 71 | 17 | 2 | 19 | 10 | 10 |
| Anaemia, 36 months (DCO: Dec 11, 2020) | 71 | 17 | 2 | 19 | 10 | 11 |
| White blood cell count decreased, 25 months (DCO: Nov 8, 2019) | 47 | 18 | 3 | 21 | 4 | 7 |
| White blood cell count decreased, 36 months (DCO: Dec 11, 2020) | 49 | 18 | 3 | 21 | 4 | 7 |
| Platelet count decreased, 25 months (DCO: Nov 8, 2019) | 47 | 4 | 0 | 4 | 3 | 7 |
| Platelet count decreased, 36 months (DCO: Dec 11, 2020) | 48 | 4 | 0 | 4 | 3 | 7 |
| Malaise, 25 months (DCO: Nov 8, 2019) | 43 | 9 | 1 | 10 | 4 | 9 |
| Malaise, 36 months (DCO: Dec 11, 2020) | 44 | 9 | 1 | 10 | 4 | 9 |
| Diarrhoea, 25 months (DCO: Nov 8, 2019) | 40 | 20 | 0 | 20 | 6 | 8 |
| Diarrhoea, 36 months (DCO: Dec 11, 2020) | 41 | 20 | 0 | 20 | 6 | 8 |
| Vomiting, 25 months (DCO: Nov 8, 2019) | 33 | 5 | 0 | 5 | 4 | 7 |
| Vomiting, 36 months (DCO: Dec 11, 2020) | 33 | 5 | 0 | 5 | 4 | 7 |
| Constipation, 25 months (DCO: Nov 8, 2019) | 30 | 13 | 1 | 14 | 5 | 5 |
| Constipation, 36 months (DCO: Dec 11, 2020) | 31 | 13 | 2 | 15 | 5 | 5 |
| Pyrexia, 25 months (DCO: Nov 8, 2019) | 30 | 8 | 2 | 10 | 3 | 6 |
| Pyrexia, 36 months (DCO: Dec 11, 2020) | 31 | 8 | 2 | 10 | 3 | 6 |
| Fatigue, 25 months (DCO: Nov 8, 2019) | 27 | 15 | 0 | 15 | 5 | 6 |
| Fatigue, 36 months (DCO: Dec 11, 2020) | 27 | 15 | 0 | 15 | 5 | 6 |
| Alopecia, 25 months (DCO: Nov 8, 2019) | 28 | 8 | 1 | 9 | 3 | 1 |
| Alopecia, 36 months (DCO: Dec 11, 2020) | 28 | 8 | 1 | 9 | 3 | 1 |
| Lymphocyte count decreased, 25 months (DCO: Nov 8, 2019) | 27 | 2 | 0 | 2 | 1 | 3 |
| Lymphocyte count decreased, 36 months (DCO: Dec 11, 2020) | 30 | 2 | 0 | 2 | 1 | 3 |
| Weight decreased, 25 months (DCO: Nov 8, 2019) | 17 | 5 | 0 | 5 | 4 | 7 |
| Weight decreased, 36 months (DCO: Dec 11, 2020) | 19 | 5 | 0 | 5 | 4 | 7 |
| Hypoalbuminaemia, 25 months (DCO: Nov 8, 2019) | 18 | 7 | 1 | 8 | 2 | 5 |
| Hypoalbuminaemia, 36 months (DCO: Dec 11, 2020) | 18 | 7 | 1 | 8 | 2 | 5 |
| Oedema peripheral, 25 months (DCO: Nov 8, 2019) | 13 | 0 | 0 | 0 | 4 | 1 |
| Oedema peripheral, 36 months (DCO: Dec 11, 2020) | 15 | 0 | 0 | 0 | 4 | 2 |
| Dysgeusia, 25 months (DCO: Nov 8, 2019) | 9 | 4 | 0 | 4 | 4 | 1 |
| Dysgeusia, 36 months (DCO: Dec 11, 2020) | 9 | 4 | 0 | 4 | 4 | 1 |
| Peripheral sensory neuropathy, 25 months (DCO: Nov 8, 2019) | 4 | 0 | 2 | 2 | 2 | 0 |
| Peripheral sensory neuropathy, 36 months (DCO: Dec 11, 2020) | 4 | 0 | 2 | 2 | 2 | 0 |
Collected over Treatment-emergent adverse event (TEAE) data were collected from baseline up to 47 days after last dose, up to 36 months postdose.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| DS-8201a | 98/125 (78.4%) | 58/125 (46.4%) | 125/125 (100%) |
| Physician's Choice Irinotecan | 46/55 (83.6%) | 15/55 (27.3%) | 54/55 (98.2%) |
| Physician's Choice Paclitaxel | 4/7 (57.1%) | 1/7 (14.3%) | 7/7 (100%) |
| Physician's Choice Overall | 50/62 (80.6%) | 16/62 (25.8%) | 61/62 (98.4%) |
| Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | 16/20 (80%) | 6/20 (30%) | 20/20 (100%) |
| Exploratory: Naïve HER2 IHC 1+, DS-8201a | 21/24 (87.5%) | 11/24 (45.8%) | 24/24 (100%) |
| Event | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| Decreased appetiteMetabolism and nutrition disorders | 13/125 | 1/55 | 0/7 | 1/62 | 2/20 | 4/24 |
| Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/125 | 0/55 | 1/7 | 1/62 | 0/20 | 0/24 |
| Disease progressionGeneral disorders | 3/125 | 2/55 | 0/7 | 2/62 | 2/20 | 0/24 |
| Gastric haemorrhageGastrointestinal disorders | 1/125 | 0/55 | 0/7 | 0/62 | 0/20 | 2/24 |
| Pneumonia bacterialInfections and infestations | 1/125 | 0/55 | 0/7 | 0/62 | 1/20 | 0/24 |
| Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/125 | 0/55 | 0/7 | 0/62 | 1/20 | 0/24 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/125 | 1/55 | 0/7 | 1/62 | 1/20 | 0/24 |
| Cerebral infarctionNervous system disorders | 0/125 | 1/55 | 0/7 | 1/62 | 1/20 | 0/24 |
| AscitesGastrointestinal disorders | 0/125 | 0/55 | 0/7 | 0/62 | 1/20 | 1/24 |
| Jaundice cholestaticHepatobiliary disorders | 3/125 | 1/55 | 0/7 | 1/62 | 1/20 | 1/24 |
| Event | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Physician's Choice Overall | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a |
|---|---|---|---|---|---|---|
| NauseaGastrointestinal disorders | 79/125 | 27/55 | 2/7 | 29/62 | 11/20 | 19/24 |
| Decreased appetiteMetabolism and nutrition disorders | 76/125 | 27/55 | 1/7 | 28/62 | 13/20 | 18/24 |
| Neutrophil count decreasedInvestigations | 79/125 | 18/55 | 3/7 | 21/62 | 8/20 | 12/24 |
| AnaemiaBlood and lymphatic system disorders | 71/125 | 17/55 | 2/7 | 19/62 | 10/20 | 11/24 |
| White blood cell count decreasedInvestigations | 49/125 | 18/55 | 3/7 | 21/62 | 4/20 | 7/24 |
| Platelet count decreasedInvestigations | 48/125 | 4/55 | 0/7 | 4/62 | 3/20 | 7/24 |
| MalaiseGeneral disorders | 44/125 | 9/55 | 1/7 | 10/62 | 4/20 | 9/24 |
| DiarrhoeaGastrointestinal disorders | 41/125 | 20/55 | 0/7 | 20/62 | 6/20 | 8/24 |
| VomitingGastrointestinal disorders | 33/125 | 5/55 | 0/7 | 5/62 | 4/20 | 7/24 |
| Weight decreasedInvestigations | 19/125 | 5/55 | 0/7 | 5/62 | 4/20 | 7/24 |
Baseline and demographic characteristics were assessed in the Full Analysis Set.
| Age, Categorical(Participants) | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a | Total |
|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 55 | 24 | 3 | 11 | 17 | 110 |
| >=65 years | 70 | 31 | 4 | 9 | 7 | 121 |
| Age, Continuous(years) | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a | Total |
|---|---|---|---|---|---|---|
| Mean | 64.2 ± 10.36 | 64.9 ± 10.54 | 63.4 ± 8.96 | 62.5 ± 10.87 | 55.5 ± 12.12 | 63.3 ± 10.86 |
| Sex: Female, Male(Participants) | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a | Total |
|---|---|---|---|---|---|---|
| Female | 30 | 13 | 2 | 4 | 7 | 56 |
| Male | 95 | 42 | 5 | 16 | 17 | 175 |
| Race (NIH/OMB)(Participants) | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 125 | 55 | 7 | 20 | 24 | 231 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | DS-8201a | Physician's Choice Irinotecan | Physician's Choice Paclitaxel | Exploratory: Naïve HER2 IHC 2+/ISH-, DS-8201a | Exploratory: Naïve HER2 IHC 1+, DS-8201a | Total |
|---|---|---|---|---|---|---|
| South Korea | 26 | 11 | 1 | 4 | 5 | 47 |
| Japan | 99 | 44 | 6 | 16 | 19 | 184 |
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
Ran from Nov 2017 to primary completion in Nov 2019, 24 months.
Results were first posted in Nov 2020, 1 year after primary completion.
Of 55 phase 2 interventional studies under Gastrointestinal Neoplasms, half reached primary completion within 44 months of starting (the median), counting those still running; a quarter within 32 and three quarters within 73. This study's 24 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Trastuzumab deruxtecan