Sarcoma, Ewing's
Conditions
Brief summary
This is a phase 1 study of anti-IGF-IR CP-751,871 in patients with solid tumors currently enrolling patients 9 years old and older with Ewing's sarcoma family of tumors (Ewing's, PNET and Askin's).
Interventions
DRUGCP-751,871
Currently dosing at 20 mg/kg, IV on day 1 of each 28 day cycle until progression or unacceptable toxicity
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Ewing's sarcoma family tumors
Exclusion criteria
* Concurrent treatment with any other anti tumor agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 150 days after the last administration of study drug | An 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 150 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Plasma Decay Half-Life (t1/2) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Plasma Decay Half-Life (t1/2) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Systemic Clearance (CL) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Systemic Clearance (CL) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| Concentration at End of Infusion (Cendinf) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Concentration at End of Infusion (Cendinf) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Volume of Distribution (Vz) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. |
| Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Volume of Distribution at Steady State (Vss) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the Vz at steady-state. |
| Volume of Distribution at Steady State (Vss) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the Vz at steady-state. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Area under the plasma concentration time-curve from zero to the last measured concentration |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Area under the plasma concentration time-curve from zero to the last measured concentration |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). |
| Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 1 | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | — |
| Human Anti-human Antibodies (HAHA) Levels | 30 minutes predose in Cycles 1 up to 61, and last scheduled follow-up visit (up to 150 days from the last dose of study drug) | HAHA were indicators of immunogenicity to figitumumab. |
| Number of Circulating Tumor Cells (CTCs) | 30 minutes predose in all cycles (up to 17); 1, 3, 7, and 14 days postdose in Cycle 1 for dose escalation and RP2D extension cohorts; and also 1 day postdose in Cycle 4 for RP2D extension cohort | Quantification of CTCs using an automated microscope system |
| Number of Insulin-like Growth Factor 1 Receptor (IGF-1R) Positive CTCs | 30 minutes predose in all cycles (up to 17); 1, 3, 7, and 14 days postdose in Cycle 1 for dose escalation and RP2D extension cohorts; and also 1 day postdose in Cycle 4 for RP2D extension cohort | Quantification of IGF-IR positive CTCs using an automated microscope system |
| Volume of Distribution (Vz) in Cycle 4 | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Figitumumab 3 mg/kg Figitumumab 3 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort. | 3 |
| Figitumumab 6 mg/kg Figitumumab 6 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort. | 3 |
| Figitumumab 10 mg/kg Figitumumab 10 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort. | 3 |
| Figitumumab 20 mg/kg Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort. | 3 |
| Figitumumab 20 mg/kg RP2D Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for RP2D extension cohort. | 13 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for RP2D ACC and sarcoma extension cohort. | 29 |
| Figitumumab 20 mg/kg RP2D ESFT Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (4 weeks in duration) for RP2D ESFT extension cohort. | 11 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 7 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Laboratory abnormality | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Progressive disease | 3 | 2 | 3 | 2 | 8 | 20 | 7 |
| Overall Study | Terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Figitumumab 3 mg/kg | Figitumumab 6 mg/kg | Figitumumab 10 mg/kg | Figitumumab 20 mg/kg | Figitumumab 20 mg/kg RP2D | Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Figitumumab 20 mg/kg RP2D ESFT |
|---|---|---|---|---|---|---|---|---|
| Age, Customized Equal to or greater than (>=) 70 years | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Age, Customized Less than (<) 70 years | 64 participants | 3 participants | 3 participants | 3 participants | 3 participants | 13 participants | 28 participants | 11 participants |
| Sex: Female, Male Female | 21 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 13 Participants | 3 Participants |
| Sex: Female, Male Male | 44 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 12 Participants | 16 Participants | 8 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 13 / 13 | 29 / 29 | 11 / 11 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 3 / 3 | 1 / 3 | 5 / 13 | 17 / 29 | 5 / 11 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An 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 150 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to 150 days after the last administration of study drug
Population: All enrolled participants who started treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Figitumumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
| Figitumumab 3 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Figitumumab 6 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
| Figitumumab 6 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
| Figitumumab 10 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
| Figitumumab 10 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 participants |
| Figitumumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
| Figitumumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
| Figitumumab 20 mg/kg RP2D | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 13 participants |
| Figitumumab 20 mg/kg RP2D | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 participants |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 29 participants |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 17 participants |
| Figitumumab 20 mg/kg RP2D ESFT | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 11 participants |
| Figitumumab 20 mg/kg RP2D ESFT | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 participants |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1
Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | 11910 mg*hr/L | Standard Deviation 4094.1 |
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | 40000 mg*hr/L | — |
| Figitumumab 10 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | 57770 mg*hr/L | Standard Deviation 28167 |
| Figitumumab 20 mg/kg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | 96300 mg*hr/L | — |
| Figitumumab 20 mg/kg RP2D | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | 136000 mg*hr/L | Standard Deviation 47622 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | 154500 mg*hr/L | Standard Deviation 27577 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | 10900 milligram*hour/liter (mg*hr/L) | Standard Deviation 3005 |
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | 27500 milligram*hour/liter (mg*hr/L) | Standard Deviation 5656.9 |
| Figitumumab 10 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | 43900 milligram*hour/liter (mg*hr/L) | Standard Deviation 19630 |
| Figitumumab 20 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | 89430 milligram*hour/liter (mg*hr/L) | Standard Deviation 11904 |
| Figitumumab 20 mg/kg RP2D | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | 107900 milligram*hour/liter (mg*hr/L) | Standard Deviation 36398 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | 102700 milligram*hour/liter (mg*hr/L) | Standard Deviation 25300 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 4 | 166500 mg*hr/L | Standard Deviation 77400 |
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 4 | 214500 mg*hr/L | Standard Deviation 67592 |
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in all cohorts except ESFT extension cohort. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 | 10900 mg*hr/L | Standard Deviation 3005 |
| Figitumumab 6 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 | 27500 mg*hr/L | Standard Deviation 5656.9 |
| Figitumumab 10 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 | 43170 mg*hr/L | Standard Deviation 20124 |
| Figitumumab 20 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 | 89430 mg*hr/L | Standard Deviation 11904 |
| Figitumumab 20 mg/kg RP2D | Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 | 104000 mg*hr/L | Standard Deviation 32547 |
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 4
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in all cohorts except ESFT extension cohort. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 4 | 193100 mg*hr/L | Standard Deviation 40001 |
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 1
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in RP2D ESFT extension cohort. N=number of participants evaluable for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 1 | 102400 mg*hr/L | Standard Deviation 25227 |
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 4
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in RP2D ESFT extension cohort. N=number of participants evaluable for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 4 | 207200 mg*hr/L | Standard Deviation 72334 |
Secondary
Concentration at End of Infusion (Cendinf) in Cycle 1
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Concentration at End of Infusion (Cendinf) in Cycle 1 | 57.50 mg/L | Standard Deviation 3.081 |
| Figitumumab 6 mg/kg | Concentration at End of Infusion (Cendinf) in Cycle 1 | 134.7 mg/L | Standard Deviation 31.754 |
| Figitumumab 10 mg/kg | Concentration at End of Infusion (Cendinf) in Cycle 1 | 211.0 mg/L | Standard Deviation 59.808 |
| Figitumumab 20 mg/kg | Concentration at End of Infusion (Cendinf) in Cycle 1 | 463.0 mg/L | Standard Deviation 97.964 |
| Figitumumab 20 mg/kg RP2D | Concentration at End of Infusion (Cendinf) in Cycle 1 | 434.3 mg/L | Standard Deviation 94.278 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Concentration at End of Infusion (Cendinf) in Cycle 1 | 386.3 mg/L | Standard Deviation 96.496 |
Secondary
Concentration at End of Infusion (Cendinf) in Cycle 4
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Concentration at End of Infusion (Cendinf) in Cycle 4 | 685.0 mg/L | Standard Deviation 167.15 |
| Figitumumab 6 mg/kg | Concentration at End of Infusion (Cendinf) in Cycle 4 | 650.3 mg/L | Standard Deviation 170.8 |
Secondary
Human Anti-human Antibodies (HAHA) Levels
HAHA were indicators of immunogenicity to figitumumab.
Time frame: 30 minutes predose in Cycles 1 up to 61, and last scheduled follow-up visit (up to 150 days from the last dose of study drug)
Population: Per protocol, the presence of HAHA would only be evaluated for those samples with plasma figitumumab concentrations below the limit of quantification (BLQ). Since none of the postdose samples in the study had figitumumab concentrations BLQ, therefore no sample was analyzed for HAHA.
Secondary
Maximum Observed Plasma Concentration (Cmax) in Cycle 1
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the pharmacokinetic (PK) parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | 57.77 milligram/liter (mg/L) | Standard Deviation 2.658 |
| Figitumumab 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | 134.7 milligram/liter (mg/L) | Standard Deviation 31.754 |
| Figitumumab 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | 211.0 milligram/liter (mg/L) | Standard Deviation 59.808 |
| Figitumumab 20 mg/kg | Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | 463.0 milligram/liter (mg/L) | Standard Deviation 97.964 |
| Figitumumab 20 mg/kg RP2D | Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | 457.5 milligram/liter (mg/L) | Standard Deviation 135.68 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Maximum Observed Plasma Concentration (Cmax) in Cycle 1 | 392.0 milligram/liter (mg/L) | Standard Deviation 90.308 |
Secondary
Maximum Observed Plasma Concentration (Cmax) in Cycle 4
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Maximum Observed Plasma Concentration (Cmax) in Cycle 4 | 697.2 mg/L | Standard Deviation 165.4 |
| Figitumumab 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) in Cycle 4 | 650.8 mg/L | Standard Deviation 169.92 |
Secondary
Number of Circulating Tumor Cells (CTCs)
Quantification of CTCs using an automated microscope system
Time frame: 30 minutes predose in all cycles (up to 17); 1, 3, 7, and 14 days postdose in Cycle 1 for dose escalation and RP2D extension cohorts; and also 1 day postdose in Cycle 4 for RP2D extension cohort
Population: Pretreatment CTCs were detected in an insufficient number of participants to analyze for any treatment effect on this pharmacodynamic biomarker.
Secondary
Number of Insulin-like Growth Factor 1 Receptor (IGF-1R) Positive CTCs
Quantification of IGF-IR positive CTCs using an automated microscope system
Time frame: 30 minutes predose in all cycles (up to 17); 1, 3, 7, and 14 days postdose in Cycle 1 for dose escalation and RP2D extension cohorts; and also 1 day postdose in Cycle 4 for RP2D extension cohort
Population: Pretreatment IGF-1R positive CTCs were detected in an insufficient number of participants to analyze for any treatment effect on this pharmacodynamic biomarker.
Secondary
Plasma Decay Half-Life (t1/2) in Cycle 1
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Plasma Decay Half-Life (t1/2) in Cycle 1 | 203.0 hours | Standard Deviation 7.071 |
| Figitumumab 6 mg/kg | Plasma Decay Half-Life (t1/2) in Cycle 1 | 226.0 hours | — |
| Figitumumab 10 mg/kg | Plasma Decay Half-Life (t1/2) in Cycle 1 | 252.3 hours | Standard Deviation 56.713 |
| Figitumumab 20 mg/kg | Plasma Decay Half-Life (t1/2) in Cycle 1 | 227.0 hours | — |
| Figitumumab 20 mg/kg RP2D | Plasma Decay Half-Life (t1/2) in Cycle 1 | 259.6 hours | Standard Deviation 80.5 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Plasma Decay Half-Life (t1/2) in Cycle 1 | 319.0 hours | Standard Deviation 8.485 |
Secondary
Plasma Decay Half-Life (t1/2) in Cycle 4
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Plasma Decay Half-Life (t1/2) in Cycle 4 | 386.0 hours | Standard Deviation 172.16 |
| Figitumumab 6 mg/kg | Plasma Decay Half-Life (t1/2) in Cycle 4 | 479.7 hours | Standard Deviation 163.59 |
Secondary
Systemic Clearance (CL) in Cycle 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Systemic Clearance (CL) in Cycle 1 | 6.435 milliliter/day/kilogram (mL/day/kg) | Standard Deviation 2.199 |
| Figitumumab 6 mg/kg | Systemic Clearance (CL) in Cycle 1 | 3.600 milliliter/day/kilogram (mL/day/kg) | — |
| Figitumumab 10 mg/kg | Systemic Clearance (CL) in Cycle 1 | 4.807 milliliter/day/kilogram (mL/day/kg) | Standard Deviation 2.059 |
| Figitumumab 20 mg/kg | Systemic Clearance (CL) in Cycle 1 | 4.990 milliliter/day/kilogram (mL/day/kg) | — |
| Figitumumab 20 mg/kg RP2D | Systemic Clearance (CL) in Cycle 1 | 3.846 milliliter/day/kilogram (mL/day/kg) | Standard Deviation 1.101 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Systemic Clearance (CL) in Cycle 1 | 3.155 milliliter/day/kilogram (mL/day/kg) | Standard Deviation 0.559 |
Secondary
Systemic Clearance (CL) in Cycle 4
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Systemic Clearance (CL) in Cycle 4 | 2.576 mL/day/kg | Standard Deviation 0.484 |
| Figitumumab 6 mg/kg | Systemic Clearance (CL) in Cycle 4 | 2.612 mL/day/kg | Standard Deviation 1.112 |
Secondary
Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | 501.0 hours | Standard Deviation 4.583 |
| Figitumumab 6 mg/kg | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | 443.0 hours | Standard Deviation 96.995 |
| Figitumumab 10 mg/kg | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | 523.7 hours | Standard Deviation 41.041 |
| Figitumumab 20 mg/kg | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | 498.3 hours | Standard Deviation 1.155 |
| Figitumumab 20 mg/kg RP2D | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | 509.5 hours | Standard Deviation 100.13 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 | 666.7 hours | Standard Deviation 3.082 |
Secondary
Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 4
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 4 | 418.7 hours | Standard Deviation 227.37 |
| Figitumumab 6 mg/kg | Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 4 | 743.7 hours | Standard Deviation 100.81 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | 8.361 hours | Standard Deviation 13.552 |
| Figitumumab 6 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | 1.147 hours | Standard Deviation 0.117 |
| Figitumumab 10 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | 1.043 hours | Standard Deviation 0.075 |
| Figitumumab 20 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | 0.678 hours | Standard Deviation 0.558 |
| Figitumumab 20 mg/kg RP2D | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | 9.394 hours | Standard Deviation 28.527 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 | 3.441 hours | Standard Deviation 7.718 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 4
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 4 | 7.541 hours | Standard Deviation 16.343 |
| Figitumumab 6 mg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 4 | 4.840 hours | Standard Deviation 9.436 |
Secondary
Volume of Distribution at Steady State (Vss) in Cycle 1
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the Vz at steady-state.
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Volume of Distribution at Steady State (Vss) in Cycle 1 | 75.05 mL/kg | Standard Deviation 20.011 |
| Figitumumab 6 mg/kg | Volume of Distribution at Steady State (Vss) in Cycle 1 | 47.90 mL/kg | — |
| Figitumumab 10 mg/kg | Volume of Distribution at Steady State (Vss) in Cycle 1 | 68.80 mL/kg | Standard Deviation 23.477 |
| Figitumumab 20 mg/kg | Volume of Distribution at Steady State (Vss) in Cycle 1 | 66.90 mL/kg | — |
| Figitumumab 20 mg/kg RP2D | Volume of Distribution at Steady State (Vss) in Cycle 1 | 59.27 mL/kg | Standard Deviation 14.765 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Volume of Distribution at Steady State (Vss) in Cycle 1 | 61.65 mL/kg | Standard Deviation 6.435 |
Secondary
Volume of Distribution at Steady State (Vss) in Cycle 4
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the Vz at steady-state.
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Volume of Distribution at Steady State (Vss) in Cycle 4 | 60.84 mL/kg | Standard Deviation 19.694 |
| Figitumumab 6 mg/kg | Volume of Distribution at Steady State (Vss) in Cycle 4 | 86.07 mL/kg | Standard Deviation 42.133 |
Secondary
Volume of Distribution (Vz) in Cycle 1
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Volume of Distribution (Vz) in Cycle 1 | 78.00 milliliter/kilogram (mL/kg) | Standard Deviation 24.183 |
| Figitumumab 6 mg/kg | Volume of Distribution (Vz) in Cycle 1 | 49.00 milliliter/kilogram (mL/kg) | — |
| Figitumumab 10 mg/kg | Volume of Distribution (Vz) in Cycle 1 | 70.47 milliliter/kilogram (mL/kg) | Standard Deviation 25.733 |
| Figitumumab 20 mg/kg | Volume of Distribution (Vz) in Cycle 1 | 68.10 milliliter/kilogram (mL/kg) | — |
| Figitumumab 20 mg/kg RP2D | Volume of Distribution (Vz) in Cycle 1 | 59.34 milliliter/kilogram (mL/kg) | Standard Deviation 14.36 |
| Figitumumab 20 mg/kg RP2D ACC+Sarcoma | Volume of Distribution (Vz) in Cycle 1 | 60.35 milliliter/kilogram (mL/kg) | Standard Deviation 9.122 |
Secondary
Volume of Distribution (Vz) in Cycle 4
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose
Population: All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 3 mg/kg | Volume of Distribution (Vz) in Cycle 4 | 61.98 mL/kg | Standard Deviation 20.741 |
| Figitumumab 6 mg/kg | Volume of Distribution (Vz) in Cycle 4 | 89.17 mL/kg | Standard Deviation 47.461 |