Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Daiichi Sankyo Co., Ltd. | INDUSTRY |
| Austin Health | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
This was a Phase 1, dose-escalation, non-randomized, open-label, single-center study of DS-8895a in patients with advanced or metastatic Ephrin type-A receptor 2 (EphA2)-positive cancers. The primary study objective was to determine the safety of DS-8895a, with secondary objectives of determining the biodistribution, tumor uptake (bioimaging), pharmacokinetics (PK), antitumor and pharmacodynamic response, and correlations between pharmacodynamics and clinical outcomes, as appropriate.
Patients received an initial ^89Zr trace-labelled infusion of DS-8895a on Day 1, followed by safety assessments, positron emission tomography (PET) imaging, and PK sampling over a 1-week period. DS-8895a was infused again on Days 8, 22, and 36. The Day 36 infusion of DS-8895a was also trace labelled with ^89Zr, with subsequent PET imaging and PK sampling. Four dose levels (1, 3, 10 and 20 mg/kg) were to be evaluated, with 3 to 6 patients entered at each dose level. Patients who responded or had stable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression, with restaging performed by computed tomography (CT) scans every 6 weeks.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DS-8895a | Experimental | Patients received infusions with DS-8895a on Days 1, 8, 22, and 36. Infusions on Days 1 and 36 were trace labelled with ^89Zr (^89Zr-Df-DS-8895a). The Day 1 dose was 0.2 mg/kg, followed by subsequent doses calculated based on individual patient body weight and dosing cohort assignment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DS-8895a 1 mg/kg | Drug | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Treatment-emergent Adverse Events | Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. | Continuously for up to 58 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a | The biodistribution and tumor uptake of ^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the ^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for [18F]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion ^89Zr-Df-DS-8895a uptake score reported for individual patients. |
Not provided
Inclusion Criteria:
Advanced or metastatic EphA2 positive cancer (based on immunohistochemistry of archived or fresh tumor tissue).
Malignant tumor that was refractory to standard treatment.
At least one reference tumor > 1 cm in size for assessment of tumor uptake of ^89Zr-Df-DS-8895a.
Expected survival of at least 3 months.
Eastern Cooperative Oncology Group performance status ≤ 1.
Within the last week prior to the first study drug administration, laboratory parameters for vital functions were to be in the normal range. Out-of-range values that were not clinically significant were permitted, except that the following parameters were to be in the specified ranges:
Calculated creatinine clearance ≥ 55 mL/min.
Age ≥ 18 years.
Able and willing to give valid written informed consent.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Andrew Scott, MD | Austin Health, Melbourne, Australia | Principal Investigator |
| Hui Gan, MD, PhD | Austin Health, Melbourne, Australia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Austin Health | Heidelberg | Victoria | 3084 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35404015 | Derived | Gan HK, Parakh S, Lee FT, Tebbutt NC, Ameratunga M, Lee ST, O'Keefe GJ, Gong SJ, Vanrenen C, Caine J, Giovannetti M, Murone C, Scott FE, Guo N, Burvenich IJG, Paine C, Macri MJ, Kotsuma M, Senaldi G, Venhaus R, Scott AM. A phase 1 safety and bioimaging trial of antibody DS-8895a against EphA2 in patients with advanced or metastatic EphA2 positive cancers. Invest New Drugs. 2022 Aug;40(4):747-755. doi: 10.1007/s10637-022-01237-3. Epub 2022 Apr 11. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | DS-8895a 1 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
| FG001 | DS-8895a 3 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
| FG002 | DS-8895a 10 mg/kg | Patients were to receive infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | DS-8895a 1 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
| 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 | Number of Patients With Treatment-emergent Adverse Events | Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. | The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a. | Posted | Count of Participants | Participants | Continuously for up to 58 weeks |
|
All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 58 weeks.
AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DS-8895a 1 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. All enrolled patients are included in AE tabulations; 1 patient was enrolled but discontinued due to SAEs prior to receiving study treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Spinal cord compression | Nervous system disorders | MedDRA (15.0) | Systematic Assessment | Grade 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Skipper PhD | Ludwig Institute for Cancer Research | 12124501539 | jskipper@lcr.org |
Not provided
Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.
Not provided
Not provided
Not provided
Not provided
|
| DS-8895a 3 mg/kg | Drug | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
|
| DS-8895a 10 mg/kg | Drug | Patients were to receive infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
|
| Up to Day 43 |
| Number of Patients With Best Overall Tumor Response | Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. | Up to 58 weeks |
| Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion | The pharmacokinetics (PK) of ^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Total Serum Clearance of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Maximum Serum Concentration of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Mean Elimination Half-life of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
| Number of Patients With Pharmacodynamic (Metabolic) Response | The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82). | Day 29 and Day 50 |
| Number of Patients With Human Anti-Human Antibody Positivity | Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response. | Up to 43 Weeks |
| Withdrawal by Subject |
|
| Serious Adverse Event During Screening |
|
| BG001 | DS-8895a 3 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| OG001 | DS-8895a 3 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. |
|
|
| Secondary | Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a | The biodistribution and tumor uptake of ^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the ^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for [18F]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion ^89Zr-Df-DS-8895a uptake score reported for individual patients. | The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a. | Posted | Count of Participants | Participants | Up to Day 43 |
|
|
|
| Secondary | Number of Patients With Best Overall Tumor Response | Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. | The Evaluable Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and completed all study procedures up to Day 50. | Posted | Count of Participants | Participants | Up to 58 weeks |
|
|
|
| Secondary | Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion | The pharmacokinetics (PK) of ^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. | Posted | Mean | Standard Deviation | hr*μg/mL | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. | Posted | Mean | Standard Deviation | mL/kg | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. | Posted | Mean | Standard Deviation | mL/hr/kg | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. | Posted | Mean | Standard Deviation | µg/mL | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion | The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. | Posted | Mean | Standard Deviation | hr | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis. | Posted | Mean | Standard Deviation | hr*μg/mL | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis. | Posted | Mean | Standard Deviation | mL/kg | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Total Serum Clearance of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis. | Posted | Mean | Standard Deviation | mL/hr/kg | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Maximum Serum Concentration of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis. | Posted | Mean | Standard Deviation | µg/mL | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Mean Elimination Half-life of DS-8895a Following the First Infusion | The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29. | The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis. | Posted | Mean | Standard Deviation | hr | Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion) |
|
|
|
| Secondary | Number of Patients With Pharmacodynamic (Metabolic) Response | The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82). | The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a. | Posted | Count of Participants | Participants | Day 29 and Day 50 |
|
|
|
| Secondary | Number of Patients With Human Anti-Human Antibody Positivity | Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response. | The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a. | Posted | Count of Participants | Participants | Up to 43 Weeks |
|
|
|
| 1 |
| 5 |
| 1 |
| 5 |
| 5 |
| 5 |
| EG001 | DS-8895a 3 mg/kg | Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. All enrolled patients are included in AE tabulations. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG002 | DS-8895a 10 mg/kg | Patients were to have received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression. All enrolled patients are included in AE tabulations; 1 patient was enrolled but discontinued due to an SAE prior to receiving study treatment. | 0 | 1 | 1 | 1 | 1 | 1 |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment | Grade 5 |
|
| Ascites | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment | Grade 3, not treatment emergent |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment | Grade 3, not treatment emergent |
|
| Cerebral infarction | Nervous system disorders | MedDRA (15.0) | Systematic Assessment | Grade 5, not treatment emergent |
|
| Cancer Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment | Grade 3, not treatment emergent |
|
| Dry eye | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Rectal stenosis | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Crepitations | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
|
| Electrocardiogram abnormal | Investigations | MedDRA (15.0) | Systematic Assessment |
|
Not provided
| Maximum Lesion Uptake Score 2 |
|
| Maximum Lesion Uptake Score 3 |
|
| Progressive Disease at Day 29 |
|