Neoplasms
Conditions
Brief summary
This is a dose-finding study; therefore, there is no hypothesis testing
Interventions
DRUGPaclitaxel + Carboplatin + CP-870,893
Paclitaxel is administered intravenously on day 1 of a 21-day cycle at a dose of 175 mg/m\^2. Carboplatin is administered intravenously on day 1 of a 21-day cycle at AUC 6. CP-870,893 is administered intravenously on DAY 3 of a 21-day cycle in escalating doses (0.1 mg/kg and 0.2 mg/kg)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients with metastatic solid tumors, for whom carboplatin and paclitaxel are appropriate; * Patients \>18 years of age; * Good performance status; * Adequate bone marrow and organ function
Exclusion criteria
* Previous treatment with any other compound that targets CD40 * Current or planned concurrent treatment with any anticancer agent; * Patients who have received bone marrow transplant; * History of autoimmune disorder * History (within the previous year) of heart failure or heart attack * Cancer-associated coagulation disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | Schedule (Sch) A Cycle 1 / Day 3 or Schedule B Cycle 1 / Day 8 up to Cycle 1 / Day 21 | Any of the following during first cycle of treatment and attributable to CP-870893: Grade (Gr) 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells/mm\^3) for ≥7 days; Gr 3 or 4 febrile neutropenia (ANC \<1000/mm\^3, fever ≥38.5 degrees Celsius; platelets ≤25,000 cells/mm\^3); ≥Gr 3 non-hematological adverse event despite optimal supportive care; ≥Gr 3 cytokine release syndrome or acute infusion reaction; failure to recover to Gr \<1 toxicity after delaying next cycle by maximum of 2 weeks; Day 3 or 8 ANC \<1000 cells/mm\^3 or platelets \<80000 cells/mm\^3, or non-hematologic toxicity ≥Gr 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours post-dose up to a maximum of 8 cycles (6 months) | Area under the serum concentration time-curve from time zero to the last measured concentration. AUClast was estimated using non-compartmental methods on the sequence of sample measurements. Mean of individual observed AUClast values measured as nanograms multiplied by micrograms per milliliter (ng\*mcg/mL). |
| Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Schedule A and Schedule B: Baseline and Day 21 of every even numbered cycle up to a maximum of 8 cycles (6 months) | Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as the disappearance of all target and nontarget lesions. PR was defined as a ≥30% decrease in the sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. |
| Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose | Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. |
| Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose | Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. |
| Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose | Assess activity of B cells (involved in production of antibodies) in presence of CP-870893. Clusters of differentiation (CD) are specific types of proteins on cell surface. CD19 is a B cell antigen receptor and is used to quantitate changes in proportion of B cells in peripheral blood as a consequence of therapy. Higher numbers may indicate a greater presence of CD19 on cell surface with increased potential for antigen response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. |
| Maximum Observed Serum Concentration (Cmax) | Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours (hrs) post-dose up to a maximum of 8 cycles (6 months) | Mean of individual observed Cmax values measured as micrograms per milliliter (mcg/mL). |
| Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose | Assess activity of B cells in the presence of CP-870893. CD23 is a low-affinity receptor that has a role in transportation in antibody feedback regulation. Agents that engage CD40 have been reported to increase CD23 expression; increased CD23 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate a potential for increased antibody response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. |
| Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose | Assess activity of B cells in presence of CP-870893. CD54 is an intercellular adhesion molecule. When activated, leukocytes bind to endothelial cells via CD54 and then transmigrate into tissues. Agents that engage CD40 have been reported to increase CD54 expression; increased CD54 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. |
| Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose | Assess activity of B cells in presence of CP-870893. CD86 is a protein expressed on antigen-presenting cells and provides co-stimulatory signals for T cell (role in cell-modulated immunity) activation. Agents that engage CD40 have been reported to increase CD86 expression; increased CD86 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. |
| Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose | Assess activity of B cells in presence of CP-870893. HLA-DR is a component of the Major Histocompatibility Complex in humans and presents antigens for recognition by the immune system. Agents that engage CD40 have been reported to increase HLA-DR expression; increased HLA-DR expression may serve as a marker for CD40 binding by CP-870893. Positive values may indicate greater presence of cells associated with potential for antibody production. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. |
| Total and Neutralizing Human Antihuman Antibody (HAHA) Titer | Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose up to a maximum of 8 cycles (6 months) | HAHA assessed as an indicator of immunogenicity to CP-870893. |
| Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose | Assess activity of B cells in the presence of CP-870893. CD40 is a costimulatory protein and is a target for CP-870893. Measurement of CD40 on white blood cells provides a measure of target modulation by CP-870893. Higher numbers may indicate potential for increased activation of antigen presenting cells. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. |
Countries
United States
Participant flow
Pre-assignment details
16 participants were screened, enrolled, and received at least 1 dose of study treatment in Schedule A. 18 participants were screened and enrolled in Schedule B; however, 2 participants discontinued before assignment to study treatment; 16 participants received at least 1 dose of study treatment in Schedule B.
Participants by arm
| Arm | Count |
|---|---|
| Schedule A - CP-870893 Participants received fixed dose chemotherapy (carboplatin and paclitaxel) IV on Day 1 of every 21 day cycle.
CP-870893 administered IV on Day 3 of every 21 day cycle with starting dose of 0.1 mg/kg (0.1 mg/kg cohort).
If 0 out of 3 or \<2 out of 6 participants in the CP-870893 0.1 mg/kg cohort experienced a dose limiting toxicity in Cycle 1, subsequent participants were enrolled in the 0.2 mg/kg dose cohort and received CP-870893 0.2 mg/kg IV on Day 3 of every 21 day cycle (0.2 mg/kg escalation cohort).
If 0 out of 3 or \<2 out of 6 participants in the CP-870893 0.2 mg/kg cohort (escalation cohort) experienced a dose limiting toxicity in Cycle 1, 0.2 mg/kg was considered the MTD. Additional participants were enrolled in the 0.2 mg/kg dose cohort and received CP-870893 0.2 mg/kg IV on Day 3 of every 21 day cycle (0.2 mg/kg expansion cohort). | 16 |
| Schedule B - CP-870893 Participants received fixed dose chemotherapy (carboplatin and paclitaxel) IV on Day 1 of every 21 day cycle.
CP-870893 administered IV on Day 8 of every 21 day cycle with starting dose of 0.1 mg/kg (0.1 mg/kg cohort).
If 0 out of 3 or \<2 out of 6 participants in the CP-870893 0.1 mg/kg cohort experienced a dose limiting toxicity in Cycle 1, subsequent participants were enrolled in the 0.2 mg/kg dose cohort and received CP-870893 0.2 mg/kg IV on Day 8 of every 21 day cycle (0.2 mg/kg escalation cohort).
If 0 out of 3 or \<2 out of 6 participants in the CP-870893 0.2 mg/kg cohort (escalation cohort) experienced a dose limiting toxicity in Cycle 1, 0.2 mg/kg was considered the MTD. Additional participants were enrolled in the 0.2 mg/kg dose cohort and received CP-870893 0.2 mg/kg IV on Day 8 of every 21 day cycle (0.2 mg/kg expansion cohort). | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 4 | 0 |
| Overall Study | Global deterioration of health | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Objective disease progression - relapse | 1 | 2 | 4 | 2 | 2 | 2 |
| Overall Study | Other | 1 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Schedule A - CP-870893 | Schedule B - CP-870893 | Total |
|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 13.4 | 54.5 years STANDARD_DEVIATION 12.7 | 56.4 years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 7 / 7 | 3 / 3 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 1 / 3 | 3 / 6 | 2 / 7 | 0 / 3 | 3 / 6 | 2 / 7 |
Outcome results
Primary
Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)
Any of the following during first cycle of treatment and attributable to CP-870893: Grade (Gr) 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells/mm\^3) for ≥7 days; Gr 3 or 4 febrile neutropenia (ANC \<1000/mm\^3, fever ≥38.5 degrees Celsius; platelets ≤25,000 cells/mm\^3); ≥Gr 3 non-hematological adverse event despite optimal supportive care; ≥Gr 3 cytokine release syndrome or acute infusion reaction; failure to recover to Gr \<1 toxicity after delaying next cycle by maximum of 2 weeks; Day 3 or 8 ANC \<1000 cells/mm\^3 or platelets \<80000 cells/mm\^3, or non-hematologic toxicity ≥Gr 2.
Time frame: Schedule (Sch) A Cycle 1 / Day 3 or Schedule B Cycle 1 / Day 8 up to Cycle 1 / Day 21
Population: Safety population: all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | 0 participants |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | 1 participants |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | 0 participants |
| Schedule B - CP-870893 0.1 mg/kg | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | 0 participants |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | 1 participants |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) | 0 participants |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the serum concentration time-curve from time zero to the last measured concentration. AUClast was estimated using non-compartmental methods on the sequence of sample measurements. Mean of individual observed AUClast values measured as nanograms multiplied by micrograms per milliliter (ng\*mcg/mL).
Time frame: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours post-dose up to a maximum of 8 cycles (6 months)
Population: Pharmacokinetic data analysis set; N=number of participants who did not have pre-dose levels of CP-870893.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 3.37 hr*mcg/mL | Standard Deviation 1.2 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 10.4 hr*mcg/mL | Standard Deviation 9.3 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 7.5 hr*mcg/mL | Standard Deviation 8.7 |
| Schedule B - CP-870893 0.1 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1.35 hr*mcg/mL | — |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 13.0 hr*mcg/mL | Standard Deviation 10.3 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 5.71 hr*mcg/mL | Standard Deviation 5.36 |
Secondary
Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax)
Assess activity of B cells (involved in production of antibodies) in presence of CP-870893. Clusters of differentiation (CD) are specific types of proteins on cell surface. CD19 is a B cell antigen receptor and is used to quantitate changes in proportion of B cells in peripheral blood as a consequence of therapy. Higher numbers may indicate a greater presence of CD19 on cell surface with increased potential for antigen response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
Population: Biomarker data analysis set: All enrolled participants who started treatment and who had baseline and sufficient on-study samples to provide interpretable results. N=Number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PD0 | 5.81 percentage of cells | Standard Deviation 1.4284 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PDMAX | 4.99 percentage of cells | Standard Deviation 0.9758 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PD0 | 9.12 percentage of cells | Standard Deviation 5.2037 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PDMAX | 7.3017 percentage of cells | Standard Deviation 5.1317 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PD0 | 11.3257 percentage of cells | Standard Deviation 6.1987 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PDMAX | 9.4614 percentage of cells | Standard Deviation 5.0745 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PD0 | 13.5233 percentage of cells | Standard Deviation 13.8885 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PDMAX | 6.7133 percentage of cells | Standard Deviation 3.8467 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PD0 | 9.42 percentage of cells | Standard Deviation 5.1037 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PDMAX | 7.7783 percentage of cells | Standard Deviation 4.4316 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PD0 | 6.5514 percentage of cells | Standard Deviation 3.3797 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax) | PDMAX | 4.6786 percentage of cells | Standard Deviation 2.9114 |
Secondary
Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax
Assess activity of B cells in the presence of CP-870893. CD23 is a low-affinity receptor that has a role in transportation in antibody feedback regulation. Agents that engage CD40 have been reported to increase CD23 expression; increased CD23 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate a potential for increased antibody response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
Population: Biomarker data analysis set; N=Number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PD0 | 71.155 percentage of cells | Standard Deviation 16.3554 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PDMAX | 22.155 percentage of cells | Standard Deviation 14.2765 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PD0 | 86.2267 percentage of cells | Standard Deviation 8.7526 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PDMAX | 36.735 percentage of cells | Standard Deviation 30.9453 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PD0 | 80.4843 percentage of cells | Standard Deviation 14.5377 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PDMAX | 20.0857 percentage of cells | Standard Deviation 8.1089 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PD0 | 90.2333 percentage of cells | Standard Deviation 5.0997 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PDMAX | 7.58 percentage of cells | Standard Deviation 4.865 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PD0 | 85.26 percentage of cells | Standard Deviation 5.2701 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PDMAX | 22.3183 percentage of cells | Standard Deviation 17.2221 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PD0 | 83.0943 percentage of cells | Standard Deviation 8.7534 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax | PDMAX | 33.3057 percentage of cells | Standard Deviation 24.057 |
Secondary
Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax
Assess activity of B cells in the presence of CP-870893. CD40 is a costimulatory protein and is a target for CP-870893. Measurement of CD40 on white blood cells provides a measure of target modulation by CP-870893. Higher numbers may indicate potential for increased activation of antigen presenting cells. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
Population: Biomarker data analysis set; N=Number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PD0 | 99.265 percentage of cells | Standard Deviation 0.7566 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PDMAX | 6.615 percentage of cells | Standard Deviation 8.2237 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PD0 | 99.8267 percentage of cells | Standard Deviation 0.2447 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PDMAX | 11.7883 percentage of cells | Standard Deviation 17.846 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PD0 | 99.0043 percentage of cells | Standard Deviation 1.4442 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PDMAX | 13.6929 percentage of cells | Standard Deviation 27.7995 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PD0 | 99.9833 percentage of cells | Standard Deviation 0.0289 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PDMAX | 0.65 percentage of cells | Standard Deviation 0.6497 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PD0 | 99.6533 percentage of cells | Standard Deviation 0.4772 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PDMAX | 18.9517 percentage of cells | Standard Deviation 38.0439 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PD0 | 88.07 percentage of cells | Standard Deviation 28.0802 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax | PDMAX | 12.6514 percentage of cells | Standard Deviation 26.8913 |
Secondary
Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax
Assess activity of B cells in presence of CP-870893. CD54 is an intercellular adhesion molecule. When activated, leukocytes bind to endothelial cells via CD54 and then transmigrate into tissues. Agents that engage CD40 have been reported to increase CD54 expression; increased CD54 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
Population: Biomarker data analysis set; N=Number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PD0 | 95.735 percentage of cells | Standard Deviation 5.8902 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PDMAX | 28.505 percentage of cells | Standard Deviation 32.0532 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PD0 | 94.7667 percentage of cells | Standard Deviation 9.0938 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PDMAX | 25.85 percentage of cells | Standard Deviation 25.9993 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PD0 | 97.9486 percentage of cells | Standard Deviation 0.8686 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PDMAX | 23.5229 percentage of cells | Standard Deviation 15.4014 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PD0 | 99.6367 percentage of cells | Standard Deviation 0.3465 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PDMAX | 1.7 percentage of cells | Standard Deviation 1.5156 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PD0 | 96.4867 percentage of cells | Standard Deviation 3.771 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PDMAX | 33.2017 percentage of cells | Standard Deviation 33.3072 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PD0 | 94.5571 percentage of cells | Standard Deviation 2.9589 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax | PDMAX | 21.1886 percentage of cells | Standard Deviation 33.3022 |
Secondary
Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax
Assess activity of B cells in presence of CP-870893. CD86 is a protein expressed on antigen-presenting cells and provides co-stimulatory signals for T cell (role in cell-modulated immunity) activation. Agents that engage CD40 have been reported to increase CD86 expression; increased CD86 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
Population: Biomarker data analysis set; N=Number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PD0 | 3.91 percentage of cells | Standard Deviation 0.4384 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PDMAX | 12.795 percentage of cells | Standard Deviation 3.0618 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PD0 | 5.8167 percentage of cells | Standard Deviation 3.4037 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PDMAX | 26.275 percentage of cells | Standard Deviation 23.1242 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PD0 | 18.7629 percentage of cells | Standard Deviation 8.2298 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PDMAX | 11.9443 percentage of cells | Standard Deviation 10.314 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PD0 | 5.5367 percentage of cells | Standard Deviation 4.4152 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PDMAX | 18.04 percentage of cells | Standard Deviation 19.9811 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PD0 | 9.23 percentage of cells | Standard Deviation 5.1565 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PDMAX | 28.0917 percentage of cells | Standard Deviation 16.5569 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PD0 | 16.7186 percentage of cells | Standard Deviation 5.4602 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax | PDMAX | 34.3943 percentage of cells | Standard Deviation 18.5593 |
Secondary
Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax
Assess activity of B cells in presence of CP-870893. HLA-DR is a component of the Major Histocompatibility Complex in humans and presents antigens for recognition by the immune system. Agents that engage CD40 have been reported to increase HLA-DR expression; increased HLA-DR expression may serve as a marker for CD40 binding by CP-870893. Positive values may indicate greater presence of cells associated with potential for antibody production. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose
Population: Biomarker data analysis set; N=Number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PD0 | 98.24 percentage of cells | Standard Deviation 2.1355 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PDMAX | 33.88 percentage of cells | Standard Deviation 38.3818 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PD0 | 98.325 percentage of cells | Standard Deviation 1.9341 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PDMAX | 27.4983 percentage of cells | Standard Deviation 24.3301 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PD0 | 99.0986 percentage of cells | Standard Deviation 0.4929 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PDMAX | 21.7857 percentage of cells | Standard Deviation 12.1245 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PD0 | 99.7833 percentage of cells | Standard Deviation 0.2021 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PDMAX | 2.7833 percentage of cells | Standard Deviation 2.501 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PD0 | 97.4 percentage of cells | Standard Deviation 3.4616 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PDMAX | 15.1783 percentage of cells | Standard Deviation 20.54 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PD0 | 98.5643 percentage of cells | Standard Deviation 1.8466 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax | PDMAX | 27.0986 percentage of cells | Standard Deviation 33.2939 |
Secondary
Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX)
Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose
Population: Pharmacokinetic data analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTO0 | 10.57 picograms per milliliter (pg/mL) | Standard Deviation 5.8106 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTOMAX | 120.67 picograms per milliliter (pg/mL) | Standard Deviation 92.5545 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTO0 | 12.10 picograms per milliliter (pg/mL) | Standard Deviation 9.5896 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTOMAX | 275.48 picograms per milliliter (pg/mL) | Standard Deviation 427.617 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTO0 | 14.52 picograms per milliliter (pg/mL) | Standard Deviation 14.674 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTOMAX | 371.22 picograms per milliliter (pg/mL) | Standard Deviation 379.799 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTO0 | 3.547 picograms per milliliter (pg/mL) | Standard Deviation 0.739 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTOMAX | 113.45 picograms per milliliter (pg/mL) | Standard Deviation 42.1629 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTO0 | 41.34 picograms per milliliter (pg/mL) | Standard Deviation 72.595 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTOMAX | 339.00 picograms per milliliter (pg/mL) | Standard Deviation 185.14 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTO0 | 8.040 picograms per milliliter (pg/mL) | Standard Deviation 6.6632 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX) | CYTOMAX | 679.40 picograms per milliliter (pg/mL) | Standard Deviation 856.849 |
Secondary
Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX
Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction.
Time frame: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose
Population: Pharmacokinetic data analysis set. CYTO0 values = the lower limit of quantitation (LLOQ).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTO0 | 15.60 pg/mL | Standard Deviation 0 |
| Schedule A - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTOMAX | 155.73 pg/mL | Standard Deviation 151.527 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTO0 | 15.60 pg/mL | Standard Deviation 0 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTOMAX | 108.90 pg/mL | Standard Deviation 148.896 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTO0 | 15.60 pg/mL | Standard Deviation 0 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTOMAX | 113.11 pg/mL | Standard Deviation 75.427 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTO0 | 15.60 pg/mL | Standard Deviation 0 |
| Schedule B - CP-870893 0.1 mg/kg | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTOMAX | 212.73 pg/mL | Standard Deviation 166.857 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTO0 | 15.60 pg/mL | Standard Deviation 0 |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTOMAX | 161.90 pg/mL | Standard Deviation 196.651 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTO0 | 15.60 pg/mL | Standard Deviation 0 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX | CYTOMAX | 675.34 pg/mL | Standard Deviation 1263.56 |
Secondary
Maximum Observed Serum Concentration (Cmax)
Mean of individual observed Cmax values measured as micrograms per milliliter (mcg/mL).
Time frame: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours (hrs) post-dose up to a maximum of 8 cycles (6 months)
Population: Pharmacokinetic data analysis set: all enrolled participants who started treatment and had baseline and sufficient on-study samples to provide interpretable results. N=number of participants who did not have pre-dose levels of CP-870893.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Maximum Observed Serum Concentration (Cmax) | 0.97 mcg/mL | Standard Deviation 0.43 |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Maximum Observed Serum Concentration (Cmax) | 1.51 mcg/mL | Standard Deviation 0.6 |
| Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort) | Maximum Observed Serum Concentration (Cmax) | 1.36 mcg/mL | Standard Deviation 0.68 |
| Schedule B - CP-870893 0.1 mg/kg | Maximum Observed Serum Concentration (Cmax) | 0.61 mcg/mL | — |
| Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort) | Maximum Observed Serum Concentration (Cmax) | 1.97 mcg/mL | Standard Deviation 0.99 |
| Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort) | Maximum Observed Serum Concentration (Cmax) | 1.06 mcg/mL | Standard Deviation 0.42 |
Secondary
Total and Neutralizing Human Antihuman Antibody (HAHA) Titer
HAHA assessed as an indicator of immunogenicity to CP-870893.
Time frame: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose up to a maximum of 8 cycles (6 months)
Population: Data was not summarized as Human antihuman responses to CP-870893 were all below the limit of quantitation (endpoint titer of 4.32).
Secondary
Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as the disappearance of all target and nontarget lesions. PR was defined as a ≥30% decrease in the sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD.
Time frame: Schedule A and Schedule B: Baseline and Day 21 of every even numbered cycle up to a maximum of 8 cycles (6 months)
Population: All response-evaluable population: included all participants who had measurable disease, a baseline tumor assessment and who started treatment were considered evaluable for analysis of tumor response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule A - CP-870893 0.1 mg/kg | Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Complete response | 0 participants |
| Schedule A - CP-870893 0.1 mg/kg | Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Partial response | 2 participants |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Complete response | 0 participants |
| Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort) | Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Partial response | 3 participants |