LUD2014-002: Safety and Bioimaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT02252211
• Collaborator: Daiichi Sankyo Co., Ltd. (Industry), Austin Health (Other)
• Enrollment: 9
• Location: 1
• Arm: 1
• Actual Duration (Months): 21
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Solid Tumor; Metastatic EphA2 Positive Cancer	Drug: DS-8895a 1 mg/kg; Drug: DS-8895a 3 mg/kg; Drug: DS-8895a 10 mg/kg	Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Intervention Model: Sequential Assignment
• Intervention Model Description: Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Safety and Bioimaging Trial of DS-8895a in Patients With Advanced or Metastatic EphA2 Positive Cancers
• Actual Study Start Date: Dec 9, 2014
• Actual Primary Completion Date: Sep 8, 2016
• Actual Study Completion Date: Sep 8, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: DS-8895a 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.

Drug: 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.; Drug: 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.; Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Treatment-emergent Adverse Events [Continuously for up to 58 weeks]

   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.

Secondary Outcome Measures

1. Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a [Up to Day 43]

   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.

2. Number of Patients With Best Overall Tumor Response [Up to 58 weeks]

   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.

3. Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

4. Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

5. Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

6. Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

7. Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

8. Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

9. Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

10. Mean Total Serum Clearance of DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

11. Mean Maximum Serum Concentration of DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

12. Mean Elimination Half-life of DS-8895a Following the First Infusion [Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-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.

13. Number of Patients With Pharmacodynamic (Metabolic) Response [Day 29 and Day 50]

    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).

14. Number of Patients With Human Anti-Human Antibody Positivity [Up to 43 Weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Advanced or metastatic EphA2 positive cancer (based on immunohistochemistry of archived or fresh tumor tissue).

2. Malignant tumor that was refractory to standard treatment.

3. At least one reference tumor > 1 cm in size for assessment of tumor uptake of ^89Zr-Df-DS-8895a.

4. Expected survival of at least 3 months.

5. Eastern Cooperative Oncology Group performance status ≤ 1.

6. 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:

• Neutrophil count ≥ 1.5 x 10^9/L

• Platelet count ≥ 90 x 10^9/L

• International normalized ratio ≤ 1.5

• Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x the upper limit of normal (ULN); ≤ 5 x ULN if liver metastases

• Serum bilirubin ≤ 1.5 x ULN

1. Calculated creatinine clearance ≥ 55 mL/min.

2. Age ≥ 18 years.

3. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Active central nervous system metastases. Definitively treated metastases were allowed if stable for 6 weeks off therapy.

2. Known immunodeficiency or human immunodeficiency virus positivity.

3. Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would have interfered with the ability of the patient to fulfill the study requirements.

4. Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to the first study drug administration that in the opinion of the investigator had > 10% risk of relapse within 12 months.

5. Significant allergic reaction to prior antibody infusions.

6. Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to the first study drug administration.

7. Regular corticosteroid, non-steroidal anti-inflammatory drug (other than paracetamol or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to the first study drug administration (intermittent dosing permitted if less than 4 doses within a 3-day period).

8. Mental impairment that could have compromised the ability to give informed consent and comply with the requirements of the study.

9. Lack of availability for clinical follow-up assessments.

10. Pregnancy or breastfeeding.

11. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Austin Health	Heidelberg	Victoria	Australia	3084

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Daiichi Sankyo Co., Ltd.
• Austin Health

Investigators

• Principal Investigator: Andrew Scott, MD, Austin Health, Melbourne, Australia
• Principal Investigator: Hui Gan, MD, PhD, Austin Health, Melbourne, Australia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT02252211
• Other Study ID Numbers: LUD2014-002
• First Posted: Sep 30, 2014
• Last Update Posted: Mar 1, 2019
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: EphA2 positive cancer; DS-8895a monoclonal antibody

Study Results

Participant Flow

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg	DS-8895a 10 mg/kg
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	5	3	1
Received Dose 1 (Day 1)	4	3	0
Received Dose 2 (Day 8)	4	3	0
Received Dose 3 (Day 22)	3	3	0
Received Dose 4 (Day 36)	1	1	0
Received Further Doses (Through Dose 24)	1	0	0
COMPLETED	0	0	0
NOT COMPLETED	5	3	1

Baseline Characteristics

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	4	3	7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.3 (7.4)	64.0 (15.1)	65.9 (10.3)
Sex: Female, Male (Count of Participants)
Female	1 25%	1 33.3%	2 28.6%
Male	3 75%	2 66.7%	5 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	3 100%	7 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 100%	2 66.7%	6 85.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 33.3%	1 14.3%
Region of Enrollment (Count of Participants)
Australia	4 100%	3 100%	7 100%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24.4 (4.2)	28.1 (6.4)	26.0 (5.1)

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment-emergent Adverse Events
Description	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.
Time Frame	Continuously for up to 58 weeks

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Any TEAE	4 100%	3 100%
Maximum grade 1 TEAE	0 0%	1 33.3%
Maximum grade 2 TEAE	4 100%	1 33.3%
Maximum grade 5 TEAE	0 0%	1 33.3%
Treatment-related TEAE	0 0%	0 0%
Treatment-emergent Serious Adverse Event	0 0%	1 33.3%
TEAE leading to study withdrawal	0 0%	1 33.3%

2. Secondary Outcome

Title	Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a
Description	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.
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Maximum Lesion Uptake Score 0 (No Uptake)	0 0%	0 0%
Maximum Lesion Uptake Score 1	4 100%	2 66.7%
Maximum Lesion Uptake Score 2	0 0%	0 0%
Maximum Lesion Uptake Score 3	0 0%	1 33.3%

3. Secondary Outcome

Title	Number of Patients With Best Overall Tumor Response
Description	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.
Time Frame	Up to 58 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	1	1
Stable disease	1 25%	0 0%
Progressive disease	0 0%	1 33.3%

4. Secondary Outcome

Title	Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Mean (Standard Deviation) [hr*μg/mL]	349.0 (24.6)	486.5 (169.7)

5. Secondary Outcome

Title	Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Mean (Standard Deviation) [mL/kg]	64.3 (7.4)	51.3 (16.8)

6. Secondary Outcome

Title	Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Mean (Standard Deviation) [mL/hr/kg]	0.6 (0.0)	0.5 (0.2)

7. Secondary Outcome

Title	Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Mean (Standard Deviation) [µg/mL]	3.1 (0.4)	4.2 (1.2)

8. Secondary Outcome

Title	Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Mean (Standard Deviation) [hr]	77.4 (5.1)	79.9 (8.3)

9. Secondary Outcome

Title	Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	3	3
Mean (Standard Deviation) [hr*μg/mL]	255.2 (14.5)	391.0 (190.0)

10. Secondary Outcome

Title	Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	3	3
Mean (Standard Deviation) [mL/kg]	51.8 (8.7)	42.1 (11.7)

11. Secondary Outcome

Title	Mean Total Serum Clearance of DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	3	3
Mean (Standard Deviation) [mL/hr/kg]	0.6 (0.1)	0.5 (0.3)

12. Secondary Outcome

Title	Mean Maximum Serum Concentration of DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	3	3
Mean (Standard Deviation) [µg/mL]	3.0 (0.3)	4.0 (1.2)

13. Secondary Outcome

Title	Mean Elimination Half-life of DS-8895a Following the First Infusion
Description	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.
Time Frame	Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	3	3
Mean (Standard Deviation) [hr]	59.3 (9.2)	65.3 (20.6)

14. Secondary Outcome

Title	Number of Patients With Pharmacodynamic (Metabolic) Response
Description	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).
Time Frame	Day 29 and Day 50

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Stable Disease at Days 29 and 50	1 25%	0 0%
Stable Disease at Day 29, Progression at Day 50	0 0%	1 33.3%
Progressive Disease at Day 29	3 75%	2 66.7%

15. Secondary Outcome

Title	Number of Patients With Human Anti-Human Antibody Positivity
Description	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.
Time Frame	Up to 43 Weeks

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.

Arm/Group Title	DS-8895a 1 mg/kg	DS-8895a 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	4	3
Positive HAHA Results (Single Sample)	1 25%	1 33.3%
Negative HAHA Results at all Time Points	3 75%	2 66.7%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	DS-8895a 1 mg/kg		DS-8895a 3 mg/kg		DS-8895a 10 mg/kg
Arm/Group Description	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.		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.		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.
All Cause Mortality
	DS-8895a 1 mg/kg		DS-8895a 3 mg/kg		DS-8895a 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/3 (33.3%)		0/1 (0%)
Serious Adverse Events
	DS-8895a 1 mg/kg		DS-8895a 3 mg/kg		DS-8895a 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/3 (33.3%)		1/1 (100%)
Gastrointestinal disorders
Ascites	1/5 (20%)		0/3 (0%)		0/1 (0%)
Small intestinal obstruction	1/5 (20%)		0/3 (0%)		0/1 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Cancer Pain	0/5 (0%)		0/3 (0%)		1/1 (100%)
Nervous system disorders
Spinal cord compression	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Cerebral infarction	1/5 (20%)		0/3 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	DS-8895a 1 mg/kg		DS-8895a 3 mg/kg		DS-8895a 10 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/3 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/5 (20%)		1/3 (33.3%)		0/1 (0%)
Eye disorders
Dry eye	1/5 (20%)		0/3 (0%)		0/1 (0%)
Gastrointestinal disorders
Diarrhoea	2/5 (40%)		0/3 (0%)		0/1 (0%)
Abdominal pain	1/5 (20%)		0/3 (0%)		0/1 (0%)
Abdominal pain upper	1/5 (20%)		0/3 (0%)		0/1 (0%)
Gastrooesophageal reflux disease	2/5 (40%)		0/3 (0%)		0/1 (0%)
Rectal stenosis	1/5 (20%)		0/3 (0%)		0/1 (0%)
Constipation	0/5 (0%)		0/3 (0%)		1/1 (100%)
General disorders
Fatigue	3/5 (60%)		0/3 (0%)		0/1 (0%)
Chills	1/5 (20%)		0/3 (0%)		0/1 (0%)
Crepitations	1/5 (20%)		0/3 (0%)		0/1 (0%)
Infections and infestations
Lower respiratory tract infection	1/5 (20%)		0/3 (0%)		0/1 (0%)
Oral candidiasis	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Upper respiratory tract infection	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Urinary Tract Infection	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Injury, poisoning and procedural complications
Fall	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Laceration	1/5 (20%)		0/3 (0%)		0/1 (0%)
Thoracic vertebral fracture	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Investigations
Electrocardiogram abnormal	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)		1/3 (33.3%)		0/1 (0%)
Gout	1/5 (20%)		0/3 (0%)		0/1 (0%)
Hyponatraemia	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Musculoskeletal chest pain	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Pathological fracture	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Nervous system disorders
Headache	1/5 (20%)		0/3 (0%)		0/1 (0%)
Presyncope	1/5 (20%)		0/3 (0%)		0/1 (0%)
Renal and urinary disorders
Dysuria	1/5 (20%)		0/3 (0%)		0/1 (0%)
Haematuria	1/5 (20%)		0/3 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/5 (20%)		0/3 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Cold sweat	1/5 (20%)		0/3 (0%)		0/1 (0%)
Hyperhidrosis	0/5 (0%)		1/3 (33.3%)		0/1 (0%)
Skin mass	1/5 (20%)		0/3 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.