Colorectal Neoplasms
Conditions
Keywords
Clinical trial, CS-1008 mAb, monoclonal antibody CS-1008, Positron-Emission Tomography, Pharmacokinetics, Pharmacodynamics, apoptosis, caspases
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.
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.
Interventions
DRUGCS-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).
Sponsors
Daiichi Sankyo
Ludwig Institute for Cancer Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 2 |
| 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. | 4 |
| 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. | 5 |
| 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. | 3 |
| 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. | 5 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Progressive disease | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.0 years | 66.0 years | 60.5 years | 65.0 years | 65.0 years | 63.0 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | 1.0 units on a scale | 0.5 units on a scale | 0.0 units on a scale | 1.0 units on a scale | 1.0 units on a scale | 1.0 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 2 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Australia | 19 Participants | 2 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 8 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 | 0 / 5 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 2 / 2 | 2 / 4 | 3 / 5 | 3 / 3 | 4 / 5 |
| serious Total, serious adverse events | 0 / 2 | 0 / 4 | 3 / 5 | 1 / 3 | 0 / 5 |
Outcome results
Primary
Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
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
Population: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 986.58 hr*μg/mL | Standard Deviation 125.11 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 5706.38 hr*μg/mL | Standard Deviation 2632.72 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 8386.68 hr*μg/mL | Standard Deviation 855.7 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 18714.05 hr*μg/mL | Standard Deviation 1511.25 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 28492 hr*μg/mL | Standard Deviation 1598 |
Primary
Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 9013 hr*μg/mL | Standard Deviation 1629 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 9772 hr*μg/mL | Standard Deviation 626 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 10990 hr*μg/mL | Standard Deviation 3205 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 10465 hr*μg/mL | Standard Deviation 3286 |
Primary
Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
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
Population: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Initial half-life | 14.51 hours | Standard Deviation 5.95 |
| Cohort 1 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Terminal half-life | 284.76 hours | Standard Deviation 0.38 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Terminal half-life | 264.89 hours | Standard Deviation 122.12 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Initial half-life | 21.52 hours | Standard Deviation 5.76 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Initial half-life | 5.29 hours | Standard Deviation 4.76 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Terminal half-life | 163.08 hours | Standard Deviation 39.86 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Initial half-life | 10.45 hours | Standard Deviation 6.85 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Terminal half-life | 243.39 hours | Standard Deviation 52.21 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Terminal half-life | 247.5 hours | Standard Deviation 52.9 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | Initial half-life | 14.73 hours | Standard Deviation 4.72 |
Primary
Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Initial half-life | 12.21 hours | Standard Deviation 6.13 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Terminal half-life | 186.2 hours | Standard Deviation 36.3 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Terminal half-life | 247.5 hours | Standard Deviation 109.3 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Initial half-life | 15.84 hours | Standard Deviation 13.25 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Initial half-life | 15.01 hours | Standard Deviation 3.48 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Terminal half-life | 347 hours | Standard Deviation 202 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Initial half-life | 15.56 hours | Standard Deviation 4.17 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | Terminal half-life | 260.5 hours | Standard Deviation 51.1 |
Primary
Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
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
Population: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 4.59 μg/mL | Standard Deviation 0.89 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 24.6 μg/mL | Standard Deviation 3.75 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 47.29 μg/mL | Standard Deviation 10.19 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 84.14 μg/mL | Standard Deviation 11 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 131.3 μg/mL | Standard Deviation 20.1 |
Primary
Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 51.08 μg/mL | Standard Deviation 11.62 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 47.10 μg/mL | Standard Deviation 12.07 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 40.98 μg/mL | Standard Deviation 9.77 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 47.38 μg/mL | Standard Deviation 9.99 |
Primary
Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
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
Population: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 14.92 mL/hr | Standard Deviation 2.5 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 12.31 mL/hr | Standard Deviation 3.38 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 18.23 mL/hr | Standard Deviation 0.51 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 12 mL/hr | Standard Deviation 2.03 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 18.52 mL/hr | Standard Deviation 2.61 |
Primary
Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 14.11 mL/hr | Standard Deviation 1.35 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 15.29 mL/hr | Standard Deviation 2 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 10.73 mL/hr | Standard Deviation 4.43 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 19.00 mL/hr | Standard Deviation 6.48 |
Primary
Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
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
Population: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 3209.83 mL | Standard Deviation 321.96 |
| Cohort 2 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 2592.36 mL | Standard Deviation 303.21 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 3329.11 mL | Standard Deviation 624.49 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 2658.70 mL | Standard Deviation 112.6 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008 | 4037 mL | Standard Deviation 425 |
Primary
Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 2510 mL | Standard Deviation 313 |
| Cohort 3 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 3272 mL | Standard Deviation 733 |
| Cohort 4 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 2742 mL | Standard Deviation 304 |
| Cohort 5 | Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008 | 3985 mL | Standard Deviation 660 |
Primary
Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions
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
Population: The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had tumor uptake.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 7/8 | 0.0042 % of injected dose/g of organ | Standard Deviation 0.0013 |
| Cohort 2 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 42/43 | 0.0045 % of injected dose/g of organ | Standard Deviation 0.0005 |
| Cohort 3 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 42/43 | 0.0061 % of injected dose/g of organ | Standard Deviation 0.0011 |
| Cohort 3 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 7/8 | 0.0063 % of injected dose/g of organ | Standard Deviation 0.0004 |
| Cohort 4 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 7/8 | 0.0044 % of injected dose/g of organ | Standard Deviation 0.0015 |
| Cohort 4 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 42/43 | 0.0044 % of injected dose/g of organ | Standard Deviation 0.0012 |
| Cohort 5 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 7/8 | 0.0043 % of injected dose/g of organ | Standard Deviation 0.0006 |
| Cohort 5 | Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions | Post-infusion tumor uptake: Day 42/43 | 0.0036 % of injected dose/g of organ | Standard Deviation 0.0007 |
Primary
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
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 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 | After Day 1 infusion: High, Specific Uptake | 0 participants |
| Cohort 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 | After Day 1 infusion: No Uptake | 2 participants |
| Cohort 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 | After Day 36 infusion: High, Specific Uptake | 0 participants |
| Cohort 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 | After Day 36 infusion: No Uptake | 2 participants |
| Cohort 2 | 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 | After Day 1 infusion: High, Specific Uptake | 3 participants |
| Cohort 2 | 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 | After Day 36 infusion: No Uptake | 1 participants |
| Cohort 2 | 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 | After Day 1 infusion: No Uptake | 1 participants |
| Cohort 2 | 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 | After Day 36 infusion: High, Specific Uptake | 3 participants |
| Cohort 3 | 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 | After Day 36 infusion: No Uptake | 1 participants |
| Cohort 3 | 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 | After Day 1 infusion: No Uptake | 2 participants |
| Cohort 3 | 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 | After Day 36 infusion: High, Specific Uptake | 3 participants |
| Cohort 3 | 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 | After Day 1 infusion: High, Specific Uptake | 3 participants |
| Cohort 4 | 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 | After Day 1 infusion: High, Specific Uptake | 3 participants |
| Cohort 4 | 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 | After Day 1 infusion: No Uptake | 0 participants |
| Cohort 4 | 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 | After Day 36 infusion: No Uptake | 0 participants |
| Cohort 4 | 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 | After Day 36 infusion: High, Specific Uptake | 3 participants |
| Cohort 5 | 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 | After Day 36 infusion: No Uptake | 2 participants |
| Cohort 5 | 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 | After Day 36 infusion: High, Specific Uptake | 3 participants |
| Cohort 5 | 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 | After Day 1 infusion: No Uptake | 2 participants |
| Cohort 5 | 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 | After Day 1 infusion: High, Specific Uptake | 3 participants |
Secondary
Number of Subjects With Best Overall Metabolic Response
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
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Subjects With Best Overall Metabolic Response | Metabolic PR | 0 Participants |
| Cohort 1 | Number of Subjects With Best Overall Metabolic Response | Metabolic PD | 1 Participants |
| Cohort 1 | Number of Subjects With Best Overall Metabolic Response | Metabolic SD | 1 Participants |
| Cohort 2 | Number of Subjects With Best Overall Metabolic Response | Metabolic SD | 2 Participants |
| Cohort 2 | Number of Subjects With Best Overall Metabolic Response | Metabolic PR | 0 Participants |
| Cohort 2 | Number of Subjects With Best Overall Metabolic Response | Metabolic PD | 2 Participants |
| Cohort 3 | Number of Subjects With Best Overall Metabolic Response | Metabolic SD | 3 Participants |
| Cohort 3 | Number of Subjects With Best Overall Metabolic Response | Metabolic PR | 0 Participants |
| Cohort 3 | Number of Subjects With Best Overall Metabolic Response | Metabolic PD | 2 Participants |
| Cohort 4 | Number of Subjects With Best Overall Metabolic Response | Metabolic PR | 1 Participants |
| Cohort 4 | Number of Subjects With Best Overall Metabolic Response | Metabolic PD | 0 Participants |
| Cohort 4 | Number of Subjects With Best Overall Metabolic Response | Metabolic SD | 2 Participants |
| Cohort 5 | Number of Subjects With Best Overall Metabolic Response | Metabolic SD | 0 Participants |
| Cohort 5 | Number of Subjects With Best Overall Metabolic Response | Metabolic PR | 0 Participants |
| Cohort 5 | Number of Subjects With Best Overall Metabolic Response | Metabolic PD | 5 Participants |
Secondary
Number of Subjects With Best Overall Tumor Response
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
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Subjects With Best Overall Tumor Response | PR | 0 Participants |
| Cohort 1 | Number of Subjects With Best Overall Tumor Response | SD | 1 Participants |
| Cohort 1 | Number of Subjects With Best Overall Tumor Response | PD | 1 Participants |
| Cohort 2 | Number of Subjects With Best Overall Tumor Response | PD | 2 Participants |
| Cohort 2 | Number of Subjects With Best Overall Tumor Response | PR | 0 Participants |
| Cohort 2 | Number of Subjects With Best Overall Tumor Response | SD | 2 Participants |
| Cohort 3 | Number of Subjects With Best Overall Tumor Response | PD | 3 Participants |
| Cohort 3 | Number of Subjects With Best Overall Tumor Response | SD | 2 Participants |
| Cohort 3 | Number of Subjects With Best Overall Tumor Response | PR | 0 Participants |
| Cohort 4 | Number of Subjects With Best Overall Tumor Response | SD | 2 Participants |
| Cohort 4 | Number of Subjects With Best Overall Tumor Response | PD | 0 Participants |
| Cohort 4 | Number of Subjects With Best Overall Tumor Response | PR | 1 Participants |
| Cohort 5 | Number of Subjects With Best Overall Tumor Response | PD | 4 Participants |
| Cohort 5 | Number of Subjects With Best Overall Tumor Response | SD | 1 Participants |
| Cohort 5 | Number of Subjects With Best Overall Tumor Response | PR | 0 Participants |