Advanced Solid Tumors
Conditions
Keywords
Treatment Non-Randomized Single Group Assignment Safety Study Neoplasms Carcinoma Cancer Malignancy
Brief summary
The purpose of this study is to determine if CVX-241 (PF-05057459) is safe and tolerable when given as weekly infusions to adult patients with advanced solid tumors.
Detailed description
The study was prematurely discontinued on 14 September 2011 due to no significant pharmacological effects (safety/PD/efficacy) through 25 mg/kg cohort, the T1/2 based on VEGF binding was shorter than expected and the current and/or higher doses were not considered feasible for further development. There were no safety concerns associated with the decision to terminate the program/study.
Interventions
DRUGCVX-241
0.3 mg/kg infusions of CVX-241 on Days 1, 8, 15, and 22 of each 28 day cycle. Weekly infusions administered until progression or unacceptable toxicity develops.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed solid tumors unresponsive to current therapy or for which there is no standard therapy. * Stage 2 only: Histologically or cytologically documented EOC or PPC with \< or equal to 3 previous anti-cancer therapies, but at least 1 prior platinum containing regimen. * Adequate coagulation, liver, and renal function. * Candidate for Dynamic Contrast-Enhanced Magnetic Resonance Imaging \[DCE-MRI\] evaluation * Eastern Cooperative Oncology Group \[ECOG\] performance status of 0 or 1
Exclusion criteria
* History of clinically significant toxicity to Vascular Endothelial Growth Factor \[VEGF\] inhibition. * Evidence of bleeding problems. * Uncontrolled hypertension. * Patients with primary brain cancer and/or non-small cell lung cancer of squamous cell histology
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Stage 1: Baseline up to Day 28 (end of cycle 1) | MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT). DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1). |
| Recommended Phase 2 Dose (RP2D) | Stage 1: Baseline up to Day 28 (end of cycle 1) | RP2D was the highest dose where 0 of 3 or less than (\<2) out of 6 participants experience a DLT. DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1 | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞)u for unbound drug. It is obtained from AUC (0 - t)u plus AUC (t - ∞)u for unbound drug. Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF). |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1 | Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF). |
| Minimum Observed Plasma Trough Concentration (Cmin) | Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1 | — |
| Systemic Clearance (CL) | Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. Due to premature termination of the study, only certain exposure-related noncompartmental PK parameters were calculated. |
| Plasma Decay Half-Life (t1/2) | Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF). |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Stage 1: Baseline up to Week 4 | DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1). |
| Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1 | Angiopoietin-2 (Ang2) and a related protein, angiopoietin-1 (Ang1) are ligands of the endothelial cell receptor Tie-2, a receptor tyrosine kinase, and are known to mediate the angiogenesis process together with VEGF and other angiogenic regulators. Ang1 stimulates the phosporylation of Tie-2, recruits pericytes to newly formed blood vessels, and promotes their maturation. Ang2 competes with Ang1 for binding of Tie-2, promotes the dissociation of pericytes, and results in unstable blood vessels. In the presence of VEGF and other angiogenic factors, endothelial cells in these unstable vessels proliferate and migrate to form new blood vessels. |
| Number of Anti Drug Antibody Samples With Positive Anti-CVX-241 Antibodies | Day 1 pre-dose of each cycle up to last dose of study medication (last dose = up to Cycle 39) | Results were summarized for overall study population as per planned analysis. |
| Objective Response Rate - Percentage of Participants With Objective Response | Every 8 weeks from start of treatment until last dose of study medication (last dose = up to Cycle 39) | Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, and Progressive Disease. |
| Participants WithTumor Response of CA-125 Epithelial Ovarian Cancer (EOC)/ Primary Peritoneal Cancer (PPC) | Stage 2 every cycle | Participants with epithelial ovarian cancer or primary peritoneal cancer having CA-125 levels greater than 2x the upper limit of normal, 2 weeks prior to starting therapy were evaluated for CA-125 response and response is defined as a 50% decrease in CA-125 from a pre-treatment sample. The response was confirmed and maintained for at least 28 days. CA-125 response was calculated as intervening samples and the 28-day confirmatory sample must be less than or equal to (within assay variability of 10%) the previous sample Progression or recurrence based on serum CA-125 is defined according to the participants baseline levels. |
| Participants With Reduction in Tumor Vascular Permeability: Blood Flow and Blood Volume as Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) | Stage 2 predose up to end of study | DCE-MRI is a non-invasive method that provides a functional assessment of microvasculature. The technique can measure changes in vascular permeability, extracellular, and extravascular and vascular volumes. Based on its ability to detect vascular changes, DCE-MRI has recently been evaluated as a biomarker of drug efficacy in clinical trials of angiogenesis inhibitors. Assessment of DCE-MRI started at the 3.0 mg/kg dose cohort. |
| Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1 | VEGF family consists of five glycoproteins known as VEGF-A, -B, -C, and -D, and placental growth factor (PlGF), which bind to three structurally similar receptor tyrosine kinases VEGFR1, VEGFR2, and VEGFR3. The different ligands have distinctive binding specificities for each of the receptors. In response to ligand binding, the VEGFRs activate distinct downstream signalling pathways. VEGFR2 is expressed in the vasculature and is the key mediator of VEGF-induced angiogenesis. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | Baseline up to 28 days after last dose of study medication (last dose = up to Cycle 39) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs and non-SAEs that occurred during the study. |
Countries
United States
Participant flow
Pre-assignment details
This study was planned to be conducted in 2 stages, however, no participant could reach out to Stage 2 due to discontinuations of all the participants in Stage 1.
Participants by arm
| Arm | Count |
|---|---|
| CVX-241 (PF-05057459) 0.3 mg/kg CVX-241 (PF-05057459) 0.3 mg/kg (milligram per kilogram) intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 3 |
| CVX-241 (PF-05057459) 1 mg/kg CVX-241 (PF-05057459) 1 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 3 |
| CVX-241 (PF-05057459) 3 mg/kg CVX-241 (PF-05057459) 3 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 3 |
| CVX-241 (PF-05057459) 6 mg/kg CVX-241 (PF-05057459) 6 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 4 |
| CVX-241 (PF-05057459) 12 mg/kg CVX-241 (PF-05057459) 12 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 4 |
| CVX-241 (PF-05057459) 15 mg/kg CVX-241 (PF-05057459) 15 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 4 |
| CVX-241 (PF-05057459) 18 mg/kg CVX-241 (PF-05057459) 18 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 4 |
| CVX-241 (PF-05057459) 25 mg/kg CVX-241 (PF-05057459) 25 mg/kg intravenous (IV) infusions once-weekly in 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for other reasons. | 5 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Global deterioration of health status | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | No longer willing to continue | 0 | 0 | 0 | 1 | 2 | 1 | 1 | 0 |
| Overall Study | Objective progression or relapse | 3 | 3 | 0 | 1 | 2 | 2 | 1 | 4 |
| Overall Study | Other | 0 | 0 | 4 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CVX-241 (PF-05057459) 0.3 mg/kg | CVX-241 (PF-05057459) 1 mg/kg | CVX-241 (PF-05057459) 3 mg/kg | CVX-241 (PF-05057459) 6 mg/kg | CVX-241 (PF-05057459) 12 mg/kg | CVX-241 (PF-05057459) 15 mg/kg | CVX-241 (PF-05057459) 18 mg/kg | CVX-241 (PF-05057459) 25 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 8.54 | 55.0 years STANDARD_DEVIATION 11.27 | 64.7 years STANDARD_DEVIATION 2.52 | 58.8 years STANDARD_DEVIATION 6.9 | 66.0 years STANDARD_DEVIATION 9.13 | 55.5 years STANDARD_DEVIATION 10.66 | 58.0 years STANDARD_DEVIATION 7.75 | 60.6 years STANDARD_DEVIATION 10.6 | 60.4 years STANDARD_DEVIATION 8.84 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 17 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 13 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 4 / 4 | 4 / 4 | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 2 / 4 | 0 / 4 | 1 / 4 | 1 / 4 | 2 / 5 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT). DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
Time frame: Stage 1: Baseline up to Day 28 (end of cycle 1)
Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication. Due to premature termination of the study MTD could not be assessed.
Primary
Recommended Phase 2 Dose (RP2D)
RP2D was the highest dose where 0 of 3 or less than (\<2) out of 6 participants experience a DLT. DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
Time frame: Stage 1: Baseline up to Day 28 (end of cycle 1)
Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication. Due to premature termination of the study RP2D could not be assessed.
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf]
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞)u for unbound drug. It is obtained from AUC (0 - t)u plus AUC (t - ∞)u for unbound drug. Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF).
Time frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication. Here n signifies those participants who were evaluable for this measure at specified time points for each arm, respectively. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 343000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 113710 |
| All Participants | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | 582900 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 609300 |
| CVX-241 (PF-05057459) 1 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 1369000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 285830 |
| CVX-241 (PF-05057459) 1 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA nanogram*hours per milliliter (ng*hr/mL) | — |
| CVX-241 (PF-05057459) 3 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 3719000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 477910 |
| CVX-241 (PF-05057459) 3 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA nanogram*hours per milliliter (ng*hr/mL) | — |
| CVX-241 (PF-05057459) 6 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 10720000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 1598800 |
| CVX-241 (PF-05057459) 6 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | 12850000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 4116800 |
| CVX-241 (PF-05057459) 12 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 16330000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 4423000 |
| CVX-241 (PF-05057459) 12 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | 21720000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 5152000 |
| CVX-241 (PF-05057459) 15 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 26510000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 4011200 |
| CVX-241 (PF-05057459) 15 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA nanogram*hours per milliliter (ng*hr/mL) | — |
| CVX-241 (PF-05057459) 18 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA nanogram*hours per milliliter (ng*hr/mL) | — |
| CVX-241 (PF-05057459) 18 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 14550000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 3040800 |
| CVX-241 (PF-05057459) 25 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 29690000 nanogram*hours per milliliter (ng*hr/mL) | Standard Deviation 12366000 |
| CVX-241 (PF-05057459) 25 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA nanogram*hours per milliliter (ng*hr/mL) | — |
Secondary
Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations
VEGF family consists of five glycoproteins known as VEGF-A, -B, -C, and -D, and placental growth factor (PlGF), which bind to three structurally similar receptor tyrosine kinases VEGFR1, VEGFR2, and VEGFR3. The different ligands have distinctive binding specificities for each of the receptors. In response to ligand binding, the VEGFRs activate distinct downstream signalling pathways. VEGFR2 is expressed in the vasculature and is the key mediator of VEGF-induced angiogenesis.
Time frame: Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
Population: Safety analysis set included all randomized participants who received at least one dose of study medication. Here n signifies those participants who were evaluable for this measure at specified time points for each arm, respectively. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 394.0 picogram/milliliter (pg/mL) | Standard Deviation 557.2 |
| All Participants | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 208.3 picogram/milliliter (pg/mL) | Standard Deviation 182.51 |
| All Participants | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 193.3 picogram/milliliter (pg/mL) | Standard Deviation 193 |
| All Participants | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 255.0 picogram/milliliter (pg/mL) | Standard Deviation 289.7 |
| All Participants | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 327.7 picogram/milliliter (pg/mL) | Standard Deviation 446.32 |
| All Participants | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 212.0 picogram/milliliter (pg/mL) | Standard Deviation 367.19 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 712.3 picogram/milliliter (pg/mL) | Standard Deviation 752.83 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 731.3 picogram/milliliter (pg/mL) | Standard Deviation 1119.4 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 564.7 picogram/milliliter (pg/mL) | Standard Deviation 680.62 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 414.7 picogram/milliliter (pg/mL) | Standard Deviation 516.34 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 826.7 picogram/milliliter (pg/mL) | Standard Deviation 911.89 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 441.0 picogram/milliliter (pg/mL) | Standard Deviation 596.73 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 544.3 picogram/milliliter (pg/mL) | Standard Deviation 269.1 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 392.3 picogram/milliliter (pg/mL) | Standard Deviation 227.87 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 525.3 picogram/milliliter (pg/mL) | Standard Deviation 282.46 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 416.7 picogram/milliliter (pg/mL) | Standard Deviation 179.06 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 636.3 picogram/milliliter (pg/mL) | Standard Deviation 298.84 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 308.7 picogram/milliliter (pg/mL) | Standard Deviation 238.3 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 196.3 picogram/milliliter (pg/mL) | Standard Deviation 73.38 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 0.0 picogram/milliliter (pg/mL) | Standard Deviation 0 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 617.3 picogram/milliliter (pg/mL) | Standard Deviation 311.94 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 316.8 picogram/milliliter (pg/mL) | Standard Deviation 228.54 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 432.5 picogram/milliliter (pg/mL) | Standard Deviation 132.14 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 230.0 picogram/milliliter (pg/mL) | Standard Deviation 199.68 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 2601.5 picogram/milliliter (pg/mL) | Standard Deviation 1405.06 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 2410.3 picogram/milliliter (pg/mL) | Standard Deviation 2133.08 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 2402.5 picogram/milliliter (pg/mL) | Standard Deviation 1582.1 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 1191.8 picogram/milliliter (pg/mL) | Standard Deviation 1309.13 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 2426.5 picogram/milliliter (pg/mL) | Standard Deviation 1615.67 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 2021.0 picogram/milliliter (pg/mL) | Standard Deviation 1153.51 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 456.3 picogram/milliliter (pg/mL) | Standard Deviation 160.88 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 434.3 picogram/milliliter (pg/mL) | Standard Deviation 212.43 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 637.5 picogram/milliliter (pg/mL) | Standard Deviation 91.29 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 444.8 picogram/milliliter (pg/mL) | Standard Deviation 231.8 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 35.3 picogram/milliliter (pg/mL) | Standard Deviation 70.5 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 553.3 picogram/milliliter (pg/mL) | Standard Deviation 573.44 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 2416.8 picogram/milliliter (pg/mL) | Standard Deviation 2247.3 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 2888.0 picogram/milliliter (pg/mL) | Standard Deviation 3733.88 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 1640.0 picogram/milliliter (pg/mL) | Standard Deviation 1232.21 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 4120.5 picogram/milliliter (pg/mL) | Standard Deviation 6036.92 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 1283.0 picogram/milliliter (pg/mL) | Standard Deviation 697.74 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 5758.8 picogram/milliliter (pg/mL) | Standard Deviation 8595.09 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY15 (n=3,3,3,4,4,4,4,5) | 2838.6 picogram/milliliter (pg/mL) | Standard Deviation 4036.03 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 3124.4 picogram/milliliter (pg/mL) | Standard Deviation 4529.62 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 2167.8 picogram/milliliter (pg/mL) | Standard Deviation 2947.41 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 2447.2 picogram/milliliter (pg/mL) | Standard Deviation 3163.16 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 3596.6 picogram/milliliter (pg/mL) | Standard Deviation 6740.7 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 3463.8 picogram/milliliter (pg/mL) | Standard Deviation 5076.53 |
Secondary
Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations
Angiopoietin-2 (Ang2) and a related protein, angiopoietin-1 (Ang1) are ligands of the endothelial cell receptor Tie-2, a receptor tyrosine kinase, and are known to mediate the angiogenesis process together with VEGF and other angiogenic regulators. Ang1 stimulates the phosporylation of Tie-2, recruits pericytes to newly formed blood vessels, and promotes their maturation. Ang2 competes with Ang1 for binding of Tie-2, promotes the dissociation of pericytes, and results in unstable blood vessels. In the presence of VEGF and other angiogenic factors, endothelial cells in these unstable vessels proliferate and migrate to form new blood vessels.
Time frame: Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1
Population: Safety analysis set included all randomized participants who received at least one dose of study medication. Here n signifies those participants who were evaluable for this measure at specified time points for each arm, respectively. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 36866.7 pg/mL | Standard Deviation 18504.14 |
| All Participants | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 46800.0 pg/mL | Standard Deviation 141.42 |
| All Participants | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 3913.3 pg/mL | Standard Deviation 701.59 |
| All Participants | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 45266.7 pg/mL | Standard Deviation 14202.93 |
| All Participants | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 32633.3 pg/mL | Standard Deviation 16323.7 |
| All Participants | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 32833.3 pg/mL | Standard Deviation 14908.16 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 128400 pg/mL | Standard Deviation 81005.43 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 130100 pg/mL | Standard Deviation 90157.25 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 84933.3 pg/mL | Standard Deviation 53814.16 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 128900 pg/mL | Standard Deviation 85837.11 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 2793.3 pg/mL | Standard Deviation 1570.01 |
| CVX-241 (PF-05057459) 1 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 126900 pg/mL | Standard Deviation 90126.63 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 195333 pg/mL | Standard Deviation 54151.02 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 214000 pg/mL | Standard Deviation 25632.01 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 5756.7 pg/mL | Standard Deviation 4274.81 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 195667 pg/mL | Standard Deviation 39703.06 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 262000 pg/mL | Standard Deviation 67638.75 |
| CVX-241 (PF-05057459) 3 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 298000 pg/mL | Standard Deviation 145578.16 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 289333 pg/mL | Standard Deviation 60302.02 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 256333 pg/mL | Standard Deviation 107802.29 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 3225.0 pg/mL | Standard Deviation 1299.55 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 272750 pg/mL | Standard Deviation 97250.11 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 228000 pg/mL | Standard Deviation 87089.99 |
| CVX-241 (PF-05057459) 6 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 296000 pg/mL | Standard Deviation 118000 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 193500 pg/mL | Standard Deviation 50836.34 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 3855.0 pg/mL | Standard Deviation 1749.79 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 255750 pg/mL | Standard Deviation 139588.38 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 224750 pg/mL | Standard Deviation 69935.09 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 174750 pg/mL | Standard Deviation 42129.76 |
| CVX-241 (PF-05057459) 12 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 199750 pg/mL | Standard Deviation 58025.14 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 140750 pg/mL | Standard Deviation 15261.61 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 122850 pg/mL | Standard Deviation 26305.07 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 2360.0 pg/mL | Standard Deviation 477.56 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 123725 pg/mL | Standard Deviation 74040.32 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 132125 pg/mL | Standard Deviation 75906.05 |
| CVX-241 (PF-05057459) 15 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 123025 pg/mL | Standard Deviation 60535.41 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 788750 pg/mL | Standard Deviation 1308363.19 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 754750 pg/mL | Standard Deviation 1197391.99 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 264000 pg/mL | Standard Deviation 124755.76 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 1040250 pg/mL | Standard Deviation 1458899.67 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 786750 pg/mL | Standard Deviation 1112399.32 |
| CVX-241 (PF-05057459) 18 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 11717.5 pg/mL | Standard Deviation 15706.56 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY8 (n=3,3,3,4,4,4,4,5) | 332360 pg/mL | Standard Deviation 175180.04 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY5 (n=3,3,3,4,4,4,4,5) | 319760 pg/mL | Standard Deviation 161304.33 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY22 (n=3,3,3,3,4,4,4,5) | 223200 pg/mL | Standard Deviation 150193.87 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY15 (n=3,3,3,3,4,4,4,5) | 208440 pg/mL | Standard Deviation 148597.92 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE2/DAY1 (n=2,3,3,3,4,4,3,4) | 233575 pg/mL | Standard Deviation 169090.48 |
| CVX-241 (PF-05057459) 25 mg/kg | Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations | CYCLE1/DAY1 (n=3,3,3,4,4,4,4,5) | 4570.0 pg/mL | Standard Deviation 2546.22 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF).
Time frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
Population: Safety analysis set included all randomized participants who received at least one dose of study medication. Here n signifies those participants who were evaluable for this measure at specified time points for each arm, respectively. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 6666 nanogram per milliliter (ng/mL) | Standard Deviation 1118.6 |
| All Participants | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 7526 nanogram per milliliter (ng/mL) | Standard Deviation 1382.5 |
| All Participants | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 8056 nanogram per milliliter (ng/mL) | Standard Deviation 1944.3 |
| All Participants | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 9454 nanogram per milliliter (ng/mL) | Standard Deviation 2011 |
| CVX-241 (PF-05057459) 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 50840 nanogram per milliliter (ng/mL) | Standard Deviation 14031 |
| CVX-241 (PF-05057459) 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 37210 nanogram per milliliter (ng/mL) | Standard Deviation 12217 |
| CVX-241 (PF-05057459) 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 27160 nanogram per milliliter (ng/mL) | Standard Deviation 5159.8 |
| CVX-241 (PF-05057459) 1 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 35490 nanogram per milliliter (ng/mL) | Standard Deviation 14492 |
| CVX-241 (PF-05057459) 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 60740 nanogram per milliliter (ng/mL) | Standard Deviation 3404.4 |
| CVX-241 (PF-05057459) 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 81410 nanogram per milliliter (ng/mL) | Standard Deviation 4650.8 |
| CVX-241 (PF-05057459) 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 64610 nanogram per milliliter (ng/mL) | Standard Deviation 6128.6 |
| CVX-241 (PF-05057459) 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 69320 nanogram per milliliter (ng/mL) | Standard Deviation 17218 |
| CVX-241 (PF-05057459) 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 201400 nanogram per milliliter (ng/mL) | Standard Deviation 34298 |
| CVX-241 (PF-05057459) 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 225200 nanogram per milliliter (ng/mL) | Standard Deviation 53613 |
| CVX-241 (PF-05057459) 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 180800 nanogram per milliliter (ng/mL) | Standard Deviation 34121 |
| CVX-241 (PF-05057459) 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 256000 nanogram per milliliter (ng/mL) | Standard Deviation 83540 |
| CVX-241 (PF-05057459) 12 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 404400 nanogram per milliliter (ng/mL) | Standard Deviation 60272 |
| CVX-241 (PF-05057459) 12 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 313400 nanogram per milliliter (ng/mL) | Standard Deviation 52077 |
| CVX-241 (PF-05057459) 12 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 350500 nanogram per milliliter (ng/mL) | Standard Deviation 53370 |
| CVX-241 (PF-05057459) 12 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 306700 nanogram per milliliter (ng/mL) | Standard Deviation 49936 |
| CVX-241 (PF-05057459) 15 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 607500 nanogram per milliliter (ng/mL) | Standard Deviation 139340 |
| CVX-241 (PF-05057459) 15 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 455900 nanogram per milliliter (ng/mL) | Standard Deviation 89920 |
| CVX-241 (PF-05057459) 15 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 489800 nanogram per milliliter (ng/mL) | Standard Deviation 197080 |
| CVX-241 (PF-05057459) 15 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 401700 nanogram per milliliter (ng/mL) | Standard Deviation 69776 |
| CVX-241 (PF-05057459) 18 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 406800 nanogram per milliliter (ng/mL) | Standard Deviation 60690 |
| CVX-241 (PF-05057459) 18 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 247900 nanogram per milliliter (ng/mL) | Standard Deviation 39013 |
| CVX-241 (PF-05057459) 18 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 277800 nanogram per milliliter (ng/mL) | Standard Deviation 26998 |
| CVX-241 (PF-05057459) 18 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 304200 nanogram per milliliter (ng/mL) | Standard Deviation 39449 |
| CVX-241 (PF-05057459) 25 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 567300 nanogram per milliliter (ng/mL) | Standard Deviation 133310 |
| CVX-241 (PF-05057459) 25 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 459100 nanogram per milliliter (ng/mL) | Standard Deviation 103170 |
| CVX-241 (PF-05057459) 25 mg/kg | Maximum Observed Plasma Concentration (Cmax) | Ang2 Binding: Cycle1/Day 22 (n=3,3,3,3,4,4,4,5) | 600200 nanogram per milliliter (ng/mL) | Standard Deviation 183030 |
| CVX-241 (PF-05057459) 25 mg/kg | Maximum Observed Plasma Concentration (Cmax) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,4,4,5) | 464400 nanogram per milliliter (ng/mL) | Standard Deviation 82330 |
Secondary
Minimum Observed Plasma Trough Concentration (Cmin)
Time frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
Population: Due to premature termination of the study Cmin data were not calculated, only certain pre-specified exposure related non compartmental pharmacokinetics (PK) parameters were calculated.
Secondary
Number of Anti Drug Antibody Samples With Positive Anti-CVX-241 Antibodies
Results were summarized for overall study population as per planned analysis.
Time frame: Day 1 pre-dose of each cycle up to last dose of study medication (last dose = up to Cycle 39)
Population: Safety analysis set included all randomized participants who received at least one dose of study medication. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Anti Drug Antibody Samples With Positive Anti-CVX-241 Antibodies | 66 samples |
Secondary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
Time frame: Stage 1: Baseline up to Week 4
Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| All Participants | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 1 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 3 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 6 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 12 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 15 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 18 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | 0 |
| CVX-241 (PF-05057459) 25 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants | — |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs and non-SAEs that occurred during the study.
Time frame: Baseline up to 28 days after last dose of study medication (last dose = up to Cycle 39)
Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 3 participants |
| All Participants | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 0 participants |
| CVX-241 (PF-05057459) 1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 3 participants |
| CVX-241 (PF-05057459) 1 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 0 participants |
| CVX-241 (PF-05057459) 3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 3 participants |
| CVX-241 (PF-05057459) 3 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 0 participants |
| CVX-241 (PF-05057459) 6 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 4 participants |
| CVX-241 (PF-05057459) 6 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 2 participants |
| CVX-241 (PF-05057459) 12 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 4 participants |
| CVX-241 (PF-05057459) 12 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 0 participants |
| CVX-241 (PF-05057459) 15 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 4 participants |
| CVX-241 (PF-05057459) 15 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 1 participants |
| CVX-241 (PF-05057459) 18 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 1 participants |
| CVX-241 (PF-05057459) 18 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 4 participants |
| CVX-241 (PF-05057459) 25 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | TEAE | 5 participants |
| CVX-241 (PF-05057459) 25 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAE | 2 participants |
Secondary
Objective Response Rate - Percentage of Participants With Objective Response
Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, and Progressive Disease.
Time frame: Every 8 weeks from start of treatment until last dose of study medication (last dose = up to Cycle 39)
Population: Safety analysis set included all randomized participants who received at least one dose of study medication. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| All Participants | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 701.59 |
| All Participants | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 14202.93 |
| CVX-241 (PF-05057459) 1 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 1570.01 |
| CVX-241 (PF-05057459) 1 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 81005.43 |
| CVX-241 (PF-05057459) 3 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 4274.81 |
| CVX-241 (PF-05057459) 3 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 25632.01 |
| CVX-241 (PF-05057459) 6 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 1299.55 |
| CVX-241 (PF-05057459) 6 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 97250.11 |
| CVX-241 (PF-05057459) 12 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 1749.79 |
| CVX-241 (PF-05057459) 12 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 58025.14 |
| CVX-241 (PF-05057459) 15 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 477.56 |
| CVX-241 (PF-05057459) 15 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 25.0 percentage of participants | 15261.61 |
| CVX-241 (PF-05057459) 18 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 1458899.67 |
| CVX-241 (PF-05057459) 18 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 15706.56 |
| CVX-241 (PF-05057459) 25 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Complete Response (CR) | 0 percentage of participants | 2546.22 |
| CVX-241 (PF-05057459) 25 mg/kg | Objective Response Rate - Percentage of Participants With Objective Response | Partial Response (PR) | 0 percentage of participants | 161304.33 |
Secondary
Participants With Reduction in Tumor Vascular Permeability: Blood Flow and Blood Volume as Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)
DCE-MRI is a non-invasive method that provides a functional assessment of microvasculature. The technique can measure changes in vascular permeability, extracellular, and extravascular and vascular volumes. Based on its ability to detect vascular changes, DCE-MRI has recently been evaluated as a biomarker of drug efficacy in clinical trials of angiogenesis inhibitors. Assessment of DCE-MRI started at the 3.0 mg/kg dose cohort.
Time frame: Stage 2 predose up to end of study
Population: Results are not reported for this measure, as, none of the participants could reach out to Stage 2 due to discontinuations of all the participants in Stage 1.
Secondary
Participants WithTumor Response of CA-125 Epithelial Ovarian Cancer (EOC)/ Primary Peritoneal Cancer (PPC)
Participants with epithelial ovarian cancer or primary peritoneal cancer having CA-125 levels greater than 2x the upper limit of normal, 2 weeks prior to starting therapy were evaluated for CA-125 response and response is defined as a 50% decrease in CA-125 from a pre-treatment sample. The response was confirmed and maintained for at least 28 days. CA-125 response was calculated as intervening samples and the 28-day confirmatory sample must be less than or equal to (within assay variability of 10%) the previous sample Progression or recurrence based on serum CA-125 is defined according to the participants baseline levels.
Time frame: Stage 2 every cycle
Population: Results are not reported for this measure, as, none of the participants could reach out to Stage 2 due to discontinuations of all the participants in Stage 1.
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Study drug was analysed using serum Angiopoietin-2 (Ang2) and plasma Vascular Endothelial Growth Factor (VEGF).
Time frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1
Population: Safety analysis set included all randomized participants who received at least one dose of study medication. Data for Stage 2 is not reported due to early termination of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 44.87 hours | Standard Deviation 5.5411 |
| All Participants | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | 58.87 hours | Standard Deviation 8.4583 |
| CVX-241 (PF-05057459) 1 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 47.20 hours | Standard Deviation 6.8986 |
| CVX-241 (PF-05057459) 1 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA hours | — |
| CVX-241 (PF-05057459) 3 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 50.53 hours | Standard Deviation 4.6544 |
| CVX-241 (PF-05057459) 3 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA hours | — |
| CVX-241 (PF-05057459) 6 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 45.38 hours | Standard Deviation 11.857 |
| CVX-241 (PF-05057459) 6 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | 57.10 hours | Standard Deviation 11.898 |
| CVX-241 (PF-05057459) 12 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 49.33 hours | Standard Deviation 6.9921 |
| CVX-241 (PF-05057459) 12 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | 62.53 hours | Standard Deviation 7.5871 |
| CVX-241 (PF-05057459) 15 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 61.87 hours | Standard Deviation 8.1978 |
| CVX-241 (PF-05057459) 15 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA hours | — |
| CVX-241 (PF-05057459) 18 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA hours | — |
| CVX-241 (PF-05057459) 18 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 52.80 hours | Standard Deviation 8.521 |
| CVX-241 (PF-05057459) 25 mg/kg | Plasma Decay Half-Life (t1/2) | VEGF Binding: Cycle1/Day 1 (n=3,3,3,4,4,3,4,5) | 50.76 hours | Standard Deviation 10.308 |
| CVX-241 (PF-05057459) 25 mg/kg | Plasma Decay Half-Life (t1/2) | Ang2 Binding: Cycle1/Day 1 (n=3,1,1,3,3,1,2,2) | NA hours | — |
Secondary
Systemic Clearance (CL)
CL is a quantitative measure of the rate at which a drug substance is removed from the body. Due to premature termination of the study, only certain exposure-related noncompartmental PK parameters were calculated.
Time frame: Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1
Population: Due to premature termination of the study, CL data were not calculated, only certain pre-specified exposure related non compartmental pharmacokinetics (PK) parameters were calculated.