Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
CP 751,871 is a fully human monoclonal antibody against the Insulin-Like Growth Factor 1 Receptor (IGF-1R). Preclinical and clinical data indicate that CP 751,871 augments the anti-tumor activity of chemotherapy. This study will identify the Maximal Tolerated Dose of CP 751,871 (or the Maximal Feasible Dose) in combination with standard gemcitabine-cisplatin chemotherapy for the treatment of advanced Non-Small Cell Lung cancer.
Interventions
DRUGCP-751,871
CP-751,871 at doses ranging from 6 to 20 mg/Kg on Day 1 of each 21-day cycle. CP-751,871 may be administered even after active comparators discontinuation, for a total number of 17 cycles (1 year).
DRUGCisplatin
Cisplatin 75\* mg/m2 or 80\* mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycles. \* 75 mg/m2 when in combination with pemetrexed, 80 mg/m2 when in combination with gemcitabine
DRUGGemcitabine
Gemcitabine 1250 mg/m2, IV on Days 1 and 8 of each 21-day cycle up to 6 cycles
DRUGPemetrexed
Pemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycle
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
* Histologically or cytologically proven diagnosis of Stage IIIB (N3 and/or T4) or Stage IV Non-Small Cell Lung Cancer in patients 18-year-old or older, with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 not amenable to curative surgery or radiation therapy and an adequate organ function (bone marrow, hepatic, renal, and cardiac) within 14 days prior to enrollment.
Exclusion criteria
* Any prior treatment for Non-Small Cell Lung Cancer including chemotherapy, biologic response modifiers or therapy with any investigational agents. * Patients with known brain metastases, spinal cord compression, uncontrolled superior vein cava syndrome or carcinomatous meningitis. * Patients with gastrointestinal abnormalities including active gastrointestinal bleeding, pre-diabetes (pre-fasting glycemia \> 120 g/dL and/or glycosylate haemoglobin level \> 7.5%), known HIV or AIDS-related illness, significant active cardiac disease or receiving chronic steroid therapy or concurrent use of growth hormones or growth hormone inhibitors or aminoglycoside antibiotics should be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT) | Start of treatment up to end of Cycle 1, Day 21 | Cycle 1 figitumumab attributed: Grade (Gr) 4 neutropenia (absolute neutrophil count \<500 cells/cubic millimeter \[mm\^3\]) \>=7 days, febrile neutropenia (Gr 3, fever \>=38.5 degrees Celsius), neutropenic infection (Gr 3 neutropenia, infection); Gr 4 thrombocytopenia (platelet \<25,000 cells/mm\^3), Gr 3 thrombocytopenia \>=7 days/bleeding; other Gr 3 not blood/bone marrow Common Terminology Criteria for Adverse Events bar gastrointestinal toxicity, treatment-managed hyperglycemia/fatigue, hypersensitivity; Gr 3-4 hyperglycemia despite treatment; fail to adequately recover to continue study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration at the End of Infusion (Cinf) for Figitumumab | Cycle 1 for dose escalation and Cycle 4 for dose expansion | Figitumumab pharmacokinetic (PK) data was analyzed using noncompartmental methods |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab | 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 1 for dose escation and 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 4 for expansion | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Figitumumab PK data was analyzed using noncompartmental methods |
| Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab | 0 (pre-dose) in Cycle 5 Day 1 | Concentration at the end of Cycle 4 |
| Maximum Observed Plasma Concentration (Cmax) for Cisplatin | 0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2 | Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence of (Cycle 2) figitumumab |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin | 0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab |
| Maximum Observed Plasma Concentration (Cmax) for Gemcitabine | 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8 | Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle) 1 and presence (Cycle 2) of figitumumab |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine | 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab |
| Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | 30 min prior to figitumumab infusion in Cycle 1 and Cycle 4, end of study, fourth follow up visit (approximately 150 days after last dose) | Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab |
| Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels | Baseline, Day 8, end of study | To monitor serum total IGF-1 levels as a potential pharmacodynamic response to figitumumab treatment |
| Maximum Observed Plasma Concentration (Cmax) for Pemetrexed | 0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2 | Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed | 0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab |
| Percentage of Participants With Objective Response or Prolonged Stabilization | Screening, from Cycle 2 onwards computerized tomography (CT) scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose) | Percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 12 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants with non measurable disease were considered having a clinical benefit response only in the case of achievement of CR. Participants who developed early progressive disease post dosing and prior to response evaluation were considered to have progressed on study. Confirmed responses were those that persisted on repeat imaging \>= 4 weeks after initial response |
| Progression-Free Survival (PFS) | Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose) | Time from the date of enrollment to date of documented disease progression, or death due to any cause |
| Duration of Response (DR) | Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose) | For responding patients (CR and PR): Time from the date that CR or PR was first recorded to the date of the first documentation of progression |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Cycle 1, up to Day 21 | The MTD was defined as the highest dose level below the maximum administered dose which caused 0 or 1 out of 6 participants to experience a DLT in that given cohort at Cycle 1 |
| Recommended Phase 2 Dose (RP2D) | Baseline to end of dose escalation, which was assessed in the last participant of the dose escalation portion of the study in Month 19 | The RP2D was determined after review and discussion by sponsor and investigators of the study data. Consideration was given to type and severity of toxicity as well as clinical suitability for long-term administration |
Countries
Belgium, Ireland, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants who received figitumumab 6, 10, 20 mg/kg and at the RP2D of 20 mg/kg with increasing infusion rates in combination with standard doses of gemcitabine and cisplatin. Participants who received figitumumab at the RP2D in combination with pemetrexed and cisplatin. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 1 | 4 | 5 | 1 | 10 |
| Overall Study | Enrolled, not treated | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Other | 2 | 2 | 2 | 3 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age Continuous | 59.2 Years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 6 / 6 | 10 / 10 | 7 / 7 | 13 / 13 |
| serious Total, serious adverse events | 3 / 6 | 2 / 3 | 3 / 6 | 7 / 10 | 2 / 7 | 8 / 13 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLT)
Cycle 1 figitumumab attributed: Grade (Gr) 4 neutropenia (absolute neutrophil count \<500 cells/cubic millimeter \[mm\^3\]) \>=7 days, febrile neutropenia (Gr 3, fever \>=38.5 degrees Celsius), neutropenic infection (Gr 3 neutropenia, infection); Gr 4 thrombocytopenia (platelet \<25,000 cells/mm\^3), Gr 3 thrombocytopenia \>=7 days/bleeding; other Gr 3 not blood/bone marrow Common Terminology Criteria for Adverse Events bar gastrointestinal toxicity, treatment-managed hyperglycemia/fatigue, hypersensitivity; Gr 3-4 hyperglycemia despite treatment; fail to adequately recover to continue study treatment
Time frame: Start of treatment up to end of Cycle 1, Day 21
Population: Safety analysis set: All enrolled participants in the dose escalation who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 6 mg/kg | Number of Participants With Dose-limiting Toxicities (DLT) | 0 participants |
| Figitumumab 10 mg/kg | Number of Participants With Dose-limiting Toxicities (DLT) | 0 participants |
| Figitumumab 20 mg/kg Dose Escalation | Number of Participants With Dose-limiting Toxicities (DLT) | 1 participants |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
Time frame: 0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin | 38.23 ng*hr/L | Standard Deviation 7.2762 |
| Figitumumab 10 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin | 45.18 ng*hr/L | Standard Deviation 15.005 |
| Figitumumab 20 mg/kg Dose Escalation | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin | 37.12 ng*hr/L | Standard Deviation 8.7975 |
| Figitumumab 20 mg/kg Expansion | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin | 48.29 ng*hr/L | Standard Deviation 13.931 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Figitumumab PK data was analyzed using noncompartmental methods
Time frame: 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 1 for dose escation and 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 4 for expansion
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab | 26020 mg*hr/L | Standard Deviation 6780.6 |
| Figitumumab 10 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab | 21500 mg*hr/L | — |
| Figitumumab 20 mg/kg Dose Escalation | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab | 84100 mg*hr/L | Standard Deviation 18983 |
| Figitumumab 20 mg/kg Expansion | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab | 121200 mg*hr/L | Standard Deviation 50493 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
Time frame: 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine | 6.665 ng*hr/L | Standard Deviation 3.0299 |
| Figitumumab 10 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine | 12.53 ng*hr/L | Standard Deviation 7.5062 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
Time frame: 0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed | 132.2 ng*hr/L | Standard Deviation 71.512 |
| Figitumumab 10 mg/kg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed | 161.6 ng*hr/L | Standard Deviation 39.335 |
Secondary
Concentration at the End of Infusion (Cinf) for Figitumumab
Figitumumab pharmacokinetic (PK) data was analyzed using noncompartmental methods
Time frame: Cycle 1 for dose escalation and Cycle 4 for dose expansion
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Concentration at the End of Infusion (Cinf) for Figitumumab | 120.4 mg/liter (L) | Standard Deviation 26.69 |
| Figitumumab 10 mg/kg | Concentration at the End of Infusion (Cinf) for Figitumumab | 137.0 mg/liter (L) | — |
| Figitumumab 20 mg/kg Dose Escalation | Concentration at the End of Infusion (Cinf) for Figitumumab | 435.0 mg/liter (L) | Standard Deviation 129.01 |
| Figitumumab 20 mg/kg Expansion | Concentration at the End of Infusion (Cinf) for Figitumumab | 513.4 mg/liter (L) | Standard Deviation 136.58 |
Secondary
Duration of Response (DR)
For responding patients (CR and PR): Time from the date that CR or PR was first recorded to the date of the first documentation of progression
Time frame: Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose)
Population: No analysis of this parameter was performed. Due to the exploratory nature of the study, the analysis of the efficacy of figitumumab was limited to the assessment of clinical benefit response and PFS.
Secondary
Maximum Observed Plasma Concentration (Cmax) for Cisplatin
Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence of (Cycle 2) figitumumab
Time frame: 0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Cisplatin | 3.816 nanogram (ng)/mL | Standard Deviation 1.5485 |
| Figitumumab 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Cisplatin | 3.880 nanogram (ng)/mL | Standard Deviation 0.849 |
| Figitumumab 20 mg/kg Dose Escalation | Maximum Observed Plasma Concentration (Cmax) for Cisplatin | 2.845 nanogram (ng)/mL | Standard Deviation 0.8804 |
| Figitumumab 20 mg/kg Expansion | Maximum Observed Plasma Concentration (Cmax) for Cisplatin | 3.490 nanogram (ng)/mL | Standard Deviation 1.1435 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Gemcitabine
Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle) 1 and presence (Cycle 2) of figitumumab
Time frame: 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Gemcitabine | 12.85 ng/L | Standard Deviation 6.9644 |
| Figitumumab 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Gemcitabine | 23.97 ng/L | Standard Deviation 18.764 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Pemetrexed
Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
Time frame: 0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Pemetrexed | 72.96 ng/mL | Standard Deviation 25.581 |
| Figitumumab 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) for Pemetrexed | 93.13 ng/mL | Standard Deviation 12.56 |
Secondary
Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab
Concentration at the end of Cycle 4
Time frame: 0 (pre-dose) in Cycle 5 Day 1
Population: PK analysis set: All enrolled participants who started treatment and had on-study samples to provide interpretable results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 6 mg/kg | Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab | 113.6 mg/L | Standard Deviation 47.266 |
Secondary
Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab
Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab
Time frame: 30 min prior to figitumumab infusion in Cycle 1 and Cycle 4, end of study, fourth follow up visit (approximately 150 days after last dose)
Population: ADA analysis set: All enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Positive | 0 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Not determined | 50.0 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Positive | 0 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Negative | 0 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Not determined | 16.7 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Positive | 0 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Positive | 0 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Negative | 83.3 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Not determined | 100 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Not determined | 83.3 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Negative | 16.7 Percentage of participants |
| Figitumumab 6 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Negative | 50.0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Negative | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Negative | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Negative | 33.3 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Positive | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Not determined | 66.7 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Positive | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Not determined | 100 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Negative | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Positive | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Not determined | 100 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Positive | 0 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Not determined | 100 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Negative | 50.0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Not determined | 100 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Not determined | 50.0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Negative | 50.0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Not determined | 50.0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Negative | 50.0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Not determined | 50.0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Negative | 0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Negative | 80.0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Not determined | 20.0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Negative | 0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Not determined | 70.0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Negative | 20.0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Not determined | 100 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Not determined | 80.0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Negative | 30.0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Not determined | 85.7 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Not determined | 0 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Negative | 100 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Not determined | 51.7 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Negative | 42.9 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Negative | 71.4 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Negative | 14.3 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Not determined | 28.6 Percentage of participants |
| Figitumumab 20 mg/kg RP2D Expansion 2.5 Infusion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Negative | 53.8 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Not determined | 0 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Not determined | 53.8 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Negative | 0 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Positive | 0 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Negative | 100 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | Follow Up - Not determined | 100 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | End of Study - Negative | 46.2 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C4D1 - Not determined | 46.2 Percentage of participants |
| Figitumumab 20 mg/kg Pemetrexed Expansion | Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab | C1D1 - Positive | 0 Percentage of participants |
Secondary
Percentage of Participants With Objective Response or Prolonged Stabilization
Percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 12 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants with non measurable disease were considered having a clinical benefit response only in the case of achievement of CR. Participants who developed early progressive disease post dosing and prior to response evaluation were considered to have progressed on study. Confirmed responses were those that persisted on repeat imaging \>= 4 weeks after initial response
Time frame: Screening, from Cycle 2 onwards computerized tomography (CT) scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose)
Population: Efficacy analysis set: All participants with measurable disease at baseline, receiving at lesast 1 dose of figitumumab with a response assessment made by the investigator according to the RECIST system.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 6 mg/kg | Percentage of Participants With Objective Response or Prolonged Stabilization | 53.3 Percentage of participants |
| Figitumumab 10 mg/kg | Percentage of Participants With Objective Response or Prolonged Stabilization | 56.5 Percentage of participants |
| Figitumumab 20 mg/kg Dose Escalation | Percentage of Participants With Objective Response or Prolonged Stabilization | 46.2 Percentage of participants |
Secondary
Progression-Free Survival (PFS)
Time from the date of enrollment to date of documented disease progression, or death due to any cause
Time frame: Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose)
Population: Efficacy analysis set: All participants with measurable disease at baseline, receiving at lesast 1 dose of figitumumab with a response assessment made by the investigator according to the RECIST system.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Figitumumab 6 mg/kg | Progression-Free Survival (PFS) | 5.7 months |
| Figitumumab 10 mg/kg | Progression-Free Survival (PFS) | 6.5 months |
| Figitumumab 20 mg/kg Dose Escalation | Progression-Free Survival (PFS) | 5.4 months |
Secondary
Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels
To monitor serum total IGF-1 levels as a potential pharmacodynamic response to figitumumab treatment
Time frame: Baseline, Day 8, end of study
Population: Biomarker analysis set: All enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Figitumumab 6 mg/kg | Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels | Baseline | 124.88 ng/mL |
| Figitumumab 6 mg/kg | Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels | End of study | 543.63 ng/mL |
Other Pre-specified
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level below the maximum administered dose which caused 0 or 1 out of 6 participants to experience a DLT in that given cohort at Cycle 1
Time frame: Cycle 1, up to Day 21
Population: Safety analysis set: All enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 6 mg/kg | Maximum Tolerated Dose (MTD) | 20 mg/kg |
Other Pre-specified
Recommended Phase 2 Dose (RP2D)
The RP2D was determined after review and discussion by sponsor and investigators of the study data. Consideration was given to type and severity of toxicity as well as clinical suitability for long-term administration
Time frame: Baseline to end of dose escalation, which was assessed in the last participant of the dose escalation portion of the study in Month 19
Population: Safety analysis set: All enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 6 mg/kg | Recommended Phase 2 Dose (RP2D) | 20 mg/kg |