A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT01220999
• Collaborator: Daiichi Sankyo, Inc. (Industry)
• Enrollment: 19
• Location: 1
• Arms: 5
• Actual Duration (Months): 20.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This was a Phase 1, open-label, single-center study of CS-1008, an immunoglobulin G subclass 1 (IgG1) humanized monoclonal antibody, in subjects with advanced colorectal carcinoma who had received ≥ 1 prior chemotherapy regimen for metastatic disease. Primary study objectives were to determine the influence of the CS-1008 dose on the biodistribution, pharmacokinetics (PK) and tumor uptake of radiolabeled CS-1008 following a single infusion and following continuous sequential doses of CS-1008. Secondary objectives were to evaluate changes in tumor metabolism, antitumor response, and changes in serum apoptosis biomarkers and tumor response markers following treatment with CS-1008.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms	Drug: CS-1008	Phase 1

Detailed Description

Eligible subjects were to be enrolled into one of 5 dose-escalation cohorts to receive CS-1008 administered weekly as an intravenous (IV) infusion over 30 ± 10 minutes. Each cohort initially comprised 2 subjects but was expanded in up to 5 subjects if additional biodistribution and/or PK data were required.

The initial infusion of CS-1008 on Day 1 was trace labeled with Indium-111 (111^{In-CS-1008; 5-7 mCi) and was investigated at escalating doses up to the standard loading dose, as follows: Cohort 1 (0.2 mg/kg), Cohort 2 (1 mg/kg), Cohort 3 (2 mg/kg), Cohort 4 (4 mg/kg), and Cohort 5 (6 mg/kg). The initial 111}In-CS-1008 dose was followed by gamma camera imaging with blood sampling over a 10-day period to evaluate biodistribution, tumor uptake, PK, and serum biomarkers. Day 8 dosing comprised non-labeled CS-1008 at doses of 6 mg/kg in Cohorts 1-3, 4 mg/kg in Cohort 4, and 2 mg/kg in Cohort 5. Subsequent weekly infusions of standard dose CS-1008 (2 mg/kg) were administered on Days 15, 22, 29, 36, and 43. The Day 36 infusion of CS-1008 was also trace labeled with 111^In (5-7 mCi), with subsequent gamma camera imaging and blood sampling.

Subjects were assessed for disease status using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, serum tumor biomarkers (carcinoembryonic antigen [CEA]), and human-anti-CS-1008-antibody development (HAHA). Subjects were assessed for changes in tumor metabolism following CS-1008 administration using computed tomography (CT) or fluorodeoxyglucose positron emission tomography (18^F-FDG PET) scans.

Cycle 1 encompassed the first 7 weeks of therapy. Within 1 week (Days 44-50) after the last infusion of CS-1008, subjects completed an End of Study/End of Cycle 1 assessment. Subjects with stable disease or better (according to RECIST version 1.1) at the Day 44-50 reassessment were permitted to receive additional 4-week cycles of CS-1008 (2 mg/kg) until disease progression, unacceptable toxicity, or subject/physician decision.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer
• Actual Study Start Date: Oct 12, 2010
• Actual Primary Completion Date: Jun 27, 2012
• Actual Study Completion Date: Jun 27, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Drug: CS-1008; CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).; Other Names: Tigatuzumab
Experimental: Cohort 2 Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Drug: CS-1008; CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).; Other Names: Tigatuzumab
Experimental: Cohort 3 Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Drug: CS-1008; CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).; Other Names: Tigatuzumab
Experimental: Cohort 4 Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Drug: CS-1008; CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).; Other Names: Tigatuzumab
Experimental: Cohort 5 Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Drug: CS-1008; CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).; Other Names: Tigatuzumab

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Tumor Uptake of 111^In-CS-1008 in Target Lesions Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions [Up to 43 days]

   Tumor localization was assessed using gamma camera imaging performed after the initial infusion of 111^In-CS-1008 on Day 1 and then on Days 2, 4/5, 7/8, and 11/12 (collectively, "After Day 1 Infusion" in the table) and after the second infusion of 111^In-CS-1008 on Day 36 and then on Days 37, 39/40, and 42/43 (collectively, "After Day 36 Infusion" in the table). Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.

2. Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions [Up to 43 days]

   Tumor localization was assessed using gamma camera imaging performed on Days 7/8 and 42/43. Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.

3. Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 [Up to 36 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).

4. Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 [Up to 36 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).

5. Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 [Up to 36 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).

6. Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 [Up to 36 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).

7. Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 [Up to 36 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).

8. Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 [Up to 50 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).

9. Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 [Up to 50 days]

   The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).

10. Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 [Up to 50 days]

    The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).

11. Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 [Up to 50 days]

    The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).

12. Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 [Up to 50 days]

    The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).

Secondary Outcome Measures

1. Number of Subjects With Best Overall Tumor Response [Up to 7 months]

   Tumor responses were evaluated using appropriate imaging and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, at Screening, at the end of every odd-numbered cycle (i.e., Cycles 1, 3, and 5, as applicable), and at the time of treatment discontinuation. Per RECIST 1.1, 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 (Eisenhauer et al. Eur J Cancer 2009;45:228-47).

2. Number of Subjects With Best Overall Metabolic Response [Up to 50 days]

   Metabolic response to CS-1008 was assessed by fluorodeoxyglucose positron emission tomography (18^F-FDG PET) at Screening, Day 15, and at the End of Cycle 1/End of Study visit (Days 44-50). For each FDG-PET performed, the maximum standardized uptake value (SUVmax) corrected for body weight for all target lesions >2 cm identified on CT imaging was calculated using region of interest (ROI). The ROI was determined with the aid of the anatomical detail provided by the CT scan. Tumor metabolic response to CS-1008 was assessed by 18^F-FDG PET/CT calculated using the target lesion with the greatest baseline SUVmax, and was categorized according to the European Organization for Research and Treatment of Cancer (EORTC) guidelines (Young et al. Eur J Cancer 1999;35:1773-82).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically proven metastatic colorectal cancer with 1 target lesion ≥ 2 cm and evaluable by gamma camera imaging. If this lesion was previously irradiated, progression must have been documented following radiotherapy.

2. Received at least 1 prior course of chemotherapy for metastatic disease.

3. Expected survival of at least 3 months.

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

5. Age ≥ 18 years old.

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

7. Within the last 1 week prior to first study drug administration, laboratory parameters for vital functions were to be in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which were to be within the ranges specified:

• Neutrophil count: ≥ 1.5 x 10^9/L

• Platelet count: ≥ 90 x 10^9/L

• International normalized ratio: ≤ 1.5

• Serum bilirubin: ≤ 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2 x ULN (≤ 5 x ULN if liver metastases)

• Calculated creatinine clearance (Cockcroft-Gault formula): ≥ 55 mL/min

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 subject to fulfill the study requirements.

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

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

6. Regular corticosteroid, nonsteroidal anti-inflammatory drug (NSAID) (other than paracetamol or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to first drug administration. Intermittent dosing of corticosteroid or NSAID was permitted if less than 4 doses within a 3-day period.

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

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

9. Pregnancy or breastfeeding.

10. Women of childbearing potential: refusal or inability to use effective means of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ludwig Institute Tumor Targeting Program, Austin Health	Melbourne	Victoria	Australia	3084

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Daiichi Sankyo, Inc.

Investigators

• Principal Investigator: Andrew M Scott, MBBS, MD, FRACP, DDU, Ludwig Institute for Cancer Research & Austin Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Full-text of Ciprotti et al 2015

Publications

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT01220999
• Other Study ID Numbers: LUD2010-002
• First Posted: Oct 14, 2010
• Last Update Posted: Sep 23, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Clinical trial; CS-1008 mAb; monoclonal antibody CS-1008; Positron-Emission Tomography; Pharmacokinetics; Pharmacodynamics; apoptosis; caspases
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Period Title: Overall Study
STARTED	2	4	5	3	5
COMPLETED	2	4	4	3	5
NOT COMPLETED	0	0	1	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Total
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Total of all reporting groups
Overall Participants	2	4	5	3	5	19
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66.0	60.5	65.0	65.0	63.0	64.0
Sex: Female, Male (Count of Participants)
Female	0 0%	2 50%	2 40%	2 66.7%	2 40%	8 42.1%
Male	2 100%	2 50%	3 60%	1 33.3%	3 60%	11 57.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	2 100%	4 100%	5 100%	3 100%	5 100%	19 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Australia	2 100%	4 100%	5 100%	3 100%	5 100%	19 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	0.5	0.0	1.0	1.0	1.0	1.0

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Tumor Uptake of 111^In-CS-1008 in Target Lesions Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions
Description	Tumor localization was assessed using gamma camera imaging performed after the initial infusion of 111^In-CS-1008 on Day 1 and then on Days 2, 4/5, 7/8, and 11/12 (collectively, "After Day 1 Infusion" in the table) and after the second infusion of 111^In-CS-1008 on Day 36 and then on Days 37, 39/40, and 42/43 (collectively, "After Day 36 Infusion" in the table). Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.
Time Frame	Up to 43 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43). One patient in Cohort 3 was prematurely withdrawn from the study on Day 36 due to symptomatic deterioration secondary to progressive disease (radiologically documented) and did not complete Cycle 1.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	3	5
After Day 1 infusion: High, Specific Uptake	0 0%	3 75%	3 60%	3 100%	3 60%
After Day 1 infusion: No Uptake	2 100%	1 25%	2 40%	0 0%	2 40%
After Day 36 infusion: High, Specific Uptake	0 0%	3 75%	3 60%	3 100%	3 60%
After Day 36 infusion: No Uptake	2 100%	1 25%	1 20%	0 0%	2 40%

2. Primary Outcome

Title	Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions
Description	Tumor localization was assessed using gamma camera imaging performed on Days 7/8 and 42/43. Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.
Time Frame	Up to 43 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had tumor uptake.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	0	3	3	3	3
Post-infusion tumor uptake: Day 7/8	0.0042 (0.0013)	0.0063 (0.0004)	0.0044 (0.0015)	0.0043 (0.0006)
Post-infusion tumor uptake: Day 42/43	0.0045 (0.0005)	0.0061 (0.0011)	0.0044 (0.0012)	0.0036 (0.0007)

3. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Time Frame	Up to 36 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	2	4
Initial half-life	14.51 (5.95)	21.52 (5.76)	5.29 (4.76)	10.45 (6.85)	14.73 (4.72)
Terminal half-life	284.76 (0.38)	264.89 (122.12)	163.08 (39.86)	243.39 (52.21)	247.5 (52.9)

4. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Time Frame	Up to 36 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	2	4
Mean (Standard Deviation) [mL]	3209.83 (321.96)	2592.36 (303.21)	3329.11 (624.49)	2658.70 (112.60)	4037 (425)

5. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Time Frame	Up to 36 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	2	4
Mean (Standard Deviation) [hr*μg/mL]	986.58 (125.11)	5706.38 (2632.72)	8386.68 (855.70)	18714.05 (1511.25)	28492 (1598)

6. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Time Frame	Up to 36 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	2	4
Mean (Standard Deviation) [mL/hr]	14.92 (2.5)	12.31 (3.38)	18.23 (0.51)	12 (2.03)	18.52 (2.61)

7. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Time Frame	Up to 36 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	2	4
Mean (Standard Deviation) [μg/mL]	4.59 (0.89)	24.6 (3.75)	47.29 (10.19)	84.14 (11)	131.3 (20.1)

8. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	0	4	3	2	3
Initial half-life	12.21 (6.13)	15.84 (13.25)	15.01 (3.48)	15.56 (4.17)
Terminal half-life	186.2 (36.3)	247.5 (109.3)	347 (202)	260.5 (51.1)

9. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	0	4	3	2	3
Mean (Standard Deviation) [mL]	2510 (313)	3272 (733)	2742 (304)	3985 (660)

10. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	0	4	3	2	3
Mean (Standard Deviation) [hr*μg/mL]	9013 (1629)	9772 (626)	10990 (3205)	10465 (3286)

11. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	0	4	3	2	3
Mean (Standard Deviation) [mL/hr]	14.11 (1.35)	15.29 (2)	10.73 (4.43)	19.00 (6.48)

12. Primary Outcome

Title	Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Description	The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had post-infusion PK samples evaluable by gamma scintillation counting.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	0	4	3	2	3
Mean (Standard Deviation) [μg/mL]	51.08 (11.62)	47.10 (12.07)	40.98 (9.77)	47.38 (9.99)

13. Secondary Outcome

Title	Number of Subjects With Best Overall Tumor Response
Description	Tumor responses were evaluated using appropriate imaging and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, at Screening, at the end of every odd-numbered cycle (i.e., Cycles 1, 3, and 5, as applicable), and at the time of treatment discontinuation. Per RECIST 1.1, 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 (Eisenhauer et al. Eur J Cancer 2009;45:228-47).
Time Frame	Up to 7 months

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received at least 1 dose of study treatment and had at least 1 applicable post-baseline response evaluation.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	3	5
PR	0 0%	0 0%	0 0%	1 33.3%	0 0%
SD	1 50%	2 50%	2 40%	2 66.7%	1 20%
PD	1 50%	2 50%	3 60%	0 0%	4 80%

14. Secondary Outcome

Title	Number of Subjects With Best Overall Metabolic Response
Description	Metabolic response to CS-1008 was assessed by fluorodeoxyglucose positron emission tomography (18^F-FDG PET) at Screening, Day 15, and at the End of Cycle 1/End of Study visit (Days 44-50). For each FDG-PET performed, the maximum standardized uptake value (SUVmax) corrected for body weight for all target lesions >2 cm identified on CT imaging was calculated using region of interest (ROI). The ROI was determined with the aid of the anatomical detail provided by the CT scan. Tumor metabolic response to CS-1008 was assessed by 18^F-FDG PET/CT calculated using the target lesion with the greatest baseline SUVmax, and was categorized according to the European Organization for Research and Treatment of Cancer (EORTC) guidelines (Young et al. Eur J Cancer 1999;35:1773-82).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

The population comprises all subjects who received at least 1 dose of study treatment and had at least 1 applicable post-baseline response evaluation.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Measure Participants	2	4	5	3	5
Metabolic PR	0 0%	0 0%	0 0%	1 33.3%	0 0%
Metabolic SD	1 50%	2 50%	3 60%	2 66.7%	0 0%
Metabolic PD	1 50%	2 50%	2 40%	0 0%	5 100%

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 that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 7 months.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), relationship to study drug, seriousness, study drug intervention, treatment, and outcome. In summaries, preferred terms were counted only once per subject at the maximum reported grade.
Arm/Group Title	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
Arm/Group Description	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.		Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.		Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.		Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.		Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
All Cause Mortality
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Serious Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)		3/5 (60%)		1/3 (33.3%)		0/5 (0%)
Gastrointestinal disorders
Rectal haemorrhage	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Nausea	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Hepatobiliary disorders
Jaundice cholestatic	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Infections and infestations
Escherichia sepsis	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Pyelonephritis	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Metabolism and nutrition disorders
Dehydration	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Nervous system disorders
Vocal cord paralysis	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		2/4 (50%)		3/5 (60%)		3/3 (100%)		4/5 (80%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Cardiac disorders
Tachycardia	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Eye disorders
Diplopia	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Lacrimation increased	1/2 (50%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Gastrointestinal disorders
Nausea	0/2 (0%)		1/4 (25%)		1/5 (20%)		2/3 (66.7%)		1/5 (20%)
Constipation	0/2 (0%)		0/4 (0%)		2/5 (40%)		1/3 (33.3%)		2/5 (40%)
Abdominal pain	1/2 (50%)		1/4 (25%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Gastrooesophageal reflux disease	0/2 (0%)		1/4 (25%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Vomiting	0/2 (0%)		0/4 (0%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)
Abdominal distension	1/2 (50%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Abdominal pain upper	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Dysphagia	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Gastritis	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Oesophagitis	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
General disorders
Fatigue	0/2 (0%)		0/4 (0%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)
Oedema peripheral	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Infections and infestations
Urinary tract infection	1/2 (50%)		0/4 (0%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)
Upper respiratory tract infection	0/2 (0%)		0/4 (0%)		0/5 (0%)		2/3 (66.7%)		0/5 (0%)
Infection	0/2 (0%)		1/4 (25%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Lower respiratory tract infection	0/2 (0%)		1/4 (25%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Oral candidiasis	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Rhinitis	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Skin candida	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Investigations
Gamma-glutamyltransferase increased	1/2 (50%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Metabolism and nutrition disorders
Anorexia	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Musculoskeletal and connective tissue disorders
Back pain	2/2 (100%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/5 (20%)
Groin pain	0/2 (0%)		1/4 (25%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Pain in extremity	1/2 (50%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Arthralgia	1/2 (50%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Muscular weakness	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Musculoskeletal chest pain	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Neck pain	1/2 (50%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)
Nervous system disorders
Dizziness	0/2 (0%)		0/4 (0%)		0/5 (0%)		2/3 (66.7%)		0/5 (0%)
Psychiatric disorders
Insomnia	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/5 (20%)
Renal and urinary disorders
Dysuria	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Renal failure acute	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/2 (0%)		1/4 (25%)		0/5 (0%)		1/3 (33.3%)		1/5 (20%)
Haemoptysis	0/2 (0%)		1/4 (25%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Dysphonia	0/2 (0%)		0/4 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)
Pleuritic pain	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Skin and subcutaneous tissue disorders
Eczema	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)
Rash	0/2 (0%)		0/4 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)
Vascular disorders
Hypertension	0/2 (0%)		0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.