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| ID | Type | Description | Link |
|---|---|---|---|
| 173790 | Registry Identifier | JAPIC CTI |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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HER2-positive cancer is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study will test an experimental drug called DS-8201a that has not been approved by the health authorities yet.
DS-8201a will be tested for safety in patients with advanced solid malignant tumors that test positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).
The expected time from the first subject's enrollment until the last subject's enrollment is approximately 8.5 months. The screening period is 28 days and each cycle of treatment is 21 days.
The data for the primary analysis will cutoff after all subjects have either discontinued the study or completed at least 3 cycles, whichever comes first. After the primary analysis, the main study will be closed and transition to the extension period.
Depending on the preliminary results of Cohort 1, Sponsor may decide whether Cohort 2 will be opened or not.
The number of treatment cycles is not fixed in this study. Subjects who continue to derive clinical benefit from the study drug in the absence of withdrawal of consent, progressive disease (PD), or unacceptable toxicity may continue the study drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: DS-8201a + Ritonavir | Experimental | DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3 |
|
| Cohort 2: DS-8201a + Itraconazole | Experimental | DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Itraconazole BID on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DS-8201a | Drug | DS-8201a is provided as a sterile lyophilized powder of DS-8201a in a glass vial, which will be dissolved and administered as an intravenous (IV) solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) For MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Maximum concentration (Cmax) was assessed for MAAA-1181a. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) for DS-8201a and total anti-HER2 antibody were assessed. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Best Objective Response as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors | Best objective response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Completed response (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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Global Clinical Leader | Daiichi Sankyo | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hokkaido Cancer Center | Sapporo | Hokkaido | 003-0804 | Japan | ||
| Hokkaido University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38231777 | Derived | Takahashi S, Bando H, Kinoshita I, Modi S, Tsurutani J, Bang YJ, Sato Y, Nakatani S, Lee C, Sugihara M, Okuda Y, Iwata H. Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies. Jpn J Clin Oncol. 2024 Apr 6;54(4):434-443. doi: 10.1093/jjco/hyad181. |
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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/
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.
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.
Based on the pharmacokinetic parameters of DS-8201a assessed in an earlier Phase 1 trial, 5.4 mg/kg DS-8201a was chosen to assess drug interactions.
A total of 40 participants who met all inclusion criteria and no exclusion criteria were enrolled and received treatment at 10 study centers in Japan, South Korea, and Taiwan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: DS-8201a + Ritonavir | Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3. |
| FG001 | Cohort 2: DS-8201a + Itraconazole | Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Demographics were assessed in the Safety Analysis Set.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: DS-8201a + Ritonavir | Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily on Day 17 of Cycle 2 until Day 21 of Cycle 3. |
| BG001 | Cohort 2: DS-8201a + Itraconazole |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ug/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
Adverse event data were collected from baseline up to approximately 9 months post-dose.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: DS-8201a + Ritonavir | Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily on Day 17 of Cycle 2 until Day 21 of Cycle 3. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disease progression | General disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Contact for Clinical Trial Information | Daiichi Sankyo | 908-992-6400 | CTRinfo@dsi.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 3, 2020 | May 4, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000614160 | trastuzumab deruxtecan |
| D019438 | Ritonavir |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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| Ritonavir | Drug | Ritonavir is a OATP1B inhibitor; an antiretroviral tablet for oral administration |
|
|
| Itraconazole | Drug | Itraconazole is a CYP3A inhibitor; an antifungal tablet for oral administration |
|
|
| Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Maximum concentration (Cmax) was assessed for MAAA-1181a. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for DS-8201a and total anti-HER2 antibody. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a. | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
| Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose |
| Objective Response Ratio (ORR) as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors | Objective response ratio (ORR) was defined as the proportion of participants who achieved CR and PR as assessed by the investigator based on 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. | Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose |
| Objective Response Rate as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors | Objective response rate (defined as participants who achieved CR and PR) was assessed by the investigator based on 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. ORR with confirmation is Objective Response Rate applying a confirmed response of CR/PR in RECIST version 1.1. | Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose |
| Sapporo |
| Hokkaido |
| 060-8648 |
| Japan |
| Kobe University Hospital | Kobe | Hyōgo | 650-0017 | Japan |
| Hamamatsu University Hospital | Hamamatsu | Shizuoka | 431-3125 | Japan |
| Shizuoka Cancer Center | Nagaizumicho | Shizuoka | 411-0934 | Japan |
| National Cancer Center Hospital | Chuo Ku | Tokyo | 104-0045 | Japan |
| The Cancer Institute Hospital of JFCR | Koto-Ku | Tokyo | 135-8550 | Japan |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Adverse Event |
|
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole BID on Day 17 of Cycle 2 followed by 200 mg QD until Day 21 of Cycle 3. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) For MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Maximum concentration (Cmax) was assessed for MAAA-1181a. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Primary | Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) for DS-8201a and total anti-HER2 antibody were assessed. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ug*d/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Primary | Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ng*d/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Primary | Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ug/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Primary | Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Maximum concentration (Cmax) was assessed for MAAA-1181a. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Primary | Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for DS-8201a and total anti-HER2 antibody. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ug*d/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Primary | Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2 | Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ng*d/mL | Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days) |
|
|
|
| Secondary | Best Objective Response as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors | Best objective response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Completed response (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. | Response was assessed in the Efficacy Analysis Set. | Posted | Count of Participants | Participants | Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose |
|
|
|
| Secondary | Objective Response Ratio (ORR) as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors | Objective response ratio (ORR) was defined as the proportion of participants who achieved CR and PR as assessed by the investigator based on 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. | Response was assessed in the Efficacy Analysis Set. | Posted | Count of Participants | Participants | Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose |
|
|
|
| Secondary | Objective Response Rate as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors | Objective response rate (defined as participants who achieved CR and PR) was assessed by the investigator based on 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. ORR with confirmation is Objective Response Rate applying a confirmed response of CR/PR in RECIST version 1.1. | Response was assessed in the Efficacy Analysis Set. | Posted | Count of Participants | Participants | Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose |
|
|
|
| 1 |
| 17 |
| 2 |
| 17 |
| 17 |
| 17 |
| EG001 | Cohort 2: DS-8201a + Itraconazole | Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole BID on Day 17 of Cycle 2 followed by 200 mg QD until Day 21 of Cycle 3. | 0 | 23 | 3 | 23 | 22 | 23 |
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Paroncyhia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Infected dermal cyst | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Osteomyelitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Akathisia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Eye discharge | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Organising pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atrophic vulvovaginitis | Reproductive system and breast disorders | MedDRA 20.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Troponin I increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Alanine aminotransferase decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Aspartate aminotransferase decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Ophthalmological examination abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Protein total decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
Not provided
Not provided
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014230 | Triazoles |
| D010879 | Piperazines |
|
| DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUC17d |
|
|
| DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUCtau |
|
|
| Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUC17d |
|
|
| Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUCtau |
|
|
| Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUC17d |
|
|
| Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUCtau |
|
|
|
| MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUC17d |
|
|
| MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUCtau |
|
|
|
| Total Anti-HER2 antibody, Cycle 3: DS-8201a + ritonavir |
|
|
| DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUCtau |
|
| Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUC17d |
|
| Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUCtau |
|
| Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUC17d |
|
| Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUCtau |
|
|
| MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUCtau |
|
| Stable disease (SD) |
|
| Non-CR/Non-PR |
|
| Progressive disease (PD) |
|
| Non evaluable |
|