Advanced Cancer, Metastatic Cancer
Conditions
Keywords
Advanced Cancer, Metastatic Cancer, Cancer
Brief summary
This study is being conducted to determine the safety of LY2523355 for the treatment of advanced and/or metastatic cancer (including Non-Hodgkin's lymphoma).
Detailed description
This study is a multi-center, non-randomized, open label, dose-escalation, Phase 1 study of intravenous LY2523355 in participants with advanced and/or metastatic cancer (including Non-Hodgkin's Lymphoma) for whom no treatment of higher priority exists.
Interventions
DRUGLY2523355
Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 alone arm is 0.125 milligrams per meter square per day (mg/m²/day).
DRUGpegfilgrastim
6 milligrams (mg) administered subcutaneously on Day 4 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of advanced and/or metastatic cancer (solid tumors or Non-Hodgkin's lymphoma) that is refractory to standard therapy or for which no proven effective therapy exists. Participants entering Part B of the study must also have a tumor that is safely amenable to serial biopsies * Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST, Therasse et al. 2000) or Revised International Working Group Lymphoma Response Criteria (Cheson et al. 2007) * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 28 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment * Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug * Females with child bearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug * Have an estimated life expectancy of greater than or equal to 12 weeks
Exclusion criteria
* Have symptomatic, untreated or uncontrolled central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastases is not required * Have current acute or chronic leukemia * Have had an autologous or allogenic bone marrow transplant * Have the following conduction abnormalities: PR \>250 milliseconds (msec), second degree or complete atrioventricular (AV) block, intraventricular conduction delay (IVCD) with QRS ≥120 msec, left branch bundle block (LBBB), right branch bundle block (RBBB), Wolf-Parkinson- White syndrome (WPW), left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), or other conduction abnormality that in the opinion of the investigator would preclude safe participation in this study. * Females who are pregnant or lactating * Known hypersensitivity to pegfilgrastim or filgrastim
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose for Phase 2 Studies | Baseline, daily up to 21 days in Cycle 1 | Recommended Phase 2 dose was determined by the maximum tolerated dose (MTD). The MTD was defined as the dose that caused \<1/3 of all participants treated with the study drug to experience a dose-limiting toxicity (DLT). A DLT was defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 3.0 Grade ≥3 nonhematological toxicity possibly or likely related to the study drug (except for nausea/vomiting/diarrhea without maximal symptomatic/prophylactic treatment); any CTCAE v 3.0 Grade ≥3 thrombocytopenia with bleeding; any CTCAE v3.0 Grade 4 hematological toxicity of \>5 days duration; any febrile neutropenia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | Cycle 1 Day 1(21-day cycle):End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime | Cmax following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim. |
| Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | Cycle 1, Day 3(21-day cycle): End of infusion | Cmax following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim. |
| Number of Participants With Clinically Significant Effects | Baseline to study completion including 30-day follow-up up to 647 days,any AE reported | Adverse events (AEs) were considered clinically significant effects. Data presented are the number of participants who experienced serious AEs (SAEs), other non-serious AEs and deaths during the study, including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | Cycle 1, Day 3(21-day cycle): End of infusion | AUC(0-∞) following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim. |
| Number of Participants With Tumor Response | Baseline to measured disease progression or discontinuation up to 617 days | Data presented are the number of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. |
| Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | Cycle 1,Day 1(21-day cycle): End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime | AUC(0-∞) following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim. |
Countries
United States
Participant flow
Pre-assignment details
Participants who completed 2 cycles of treatment are considered having completed study.
Participants by arm
| Arm | Count |
|---|---|
| 0.125 mg/m²/Day LY 0.125 milligrams per meter square per day (mg/m²/day) LY2523355 (LY) was administered as an intravenous (IV) infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until progressive disease (PD), unacceptable toxicity or other withdrawal criterion is met | 1 |
| 0.25 mg/m²/Day LY 0.25 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 1 |
| 0.5 mg/m²/Day LY 0.5 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 1 |
| 1.0 mg/m²/Day LY 1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 3 |
| 2.0 mg/m²/Day LY 2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met | 3 |
| 4.0 mg/m²/Day LY 4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 13 |
| 5.0 mg/m²/Day LY 5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 5 |
| 6.0 mg/m²/Day LY 6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 3 |
| 4.0 mg/m²/Day LY + 6 mg PEG 4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles.
6 milligrams (mg) pegfilgrastim (PEG) was administered subcutaneously (SC) on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received.
Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 3 |
| 6.0 mg/m²/Day LY + 6 mg PEG 6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles.
6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received.
Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 18 |
| 7.0 mg/m²/Day LY + 6 mg PEG 7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles.
6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received.
Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met. | 3 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive Disease | 1 | 1 | 0 | 1 | 2 | 3 | 1 | 1 | 1 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 0.125 mg/m²/Day LY | Total | 7.0 mg/m²/Day LY + 6 mg PEG | 6.0 mg/m²/Day LY + 6 mg PEG | 4.0 mg/m²/Day LY + 6 mg PEG | 6.0 mg/m²/Day LY | 5.0 mg/m²/Day LY | 4.0 mg/m²/Day LY | 2.0 mg/m²/Day LY | 1.0 mg/m²/Day LY | 0.5 mg/m²/Day LY | 0.25 mg/m²/Day LY |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.01 years | 60.27 years STANDARD_DEVIATION 10.78 | 60.13 years STANDARD_DEVIATION 0.49 | 56.82 years STANDARD_DEVIATION 12.09 | 66.97 years STANDARD_DEVIATION 17.19 | 67.26 years STANDARD_DEVIATION 5.88 | 63.38 years STANDARD_DEVIATION 12.5 | 59.79 years STANDARD_DEVIATION 8.75 | 61.30 years STANDARD_DEVIATION 13.91 | 60.78 years STANDARD_DEVIATION 12.84 | 52.37 years | 71.20 years |
| Race/Ethnicity, Customized African | 1 Participants | 9 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 0 Participants | 38 Participants | 2 Participants | 10 Participants | 2 Participants | 3 Participants | 5 Participants | 10 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 5 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 1 Participants | 54 Participants | 3 Participants | 18 Participants | 3 Participants | 3 Participants | 5 Participants | 13 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 37 Participants | 2 Participants | 12 Participants | 3 Participants | 1 Participants | 3 Participants | 9 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 17 Participants | 1 Participants | 6 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 0 / 1 | 2 / 3 | 3 / 3 | 13 / 13 | 3 / 3 | 5 / 5 | 3 / 3 | 18 / 18 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 3 | 0 / 3 | 5 / 13 | 0 / 3 | 3 / 5 | 3 / 3 | 11 / 18 | 3 / 3 |
Outcome results
Primary
Recommended Dose for Phase 2 Studies
Recommended Phase 2 dose was determined by the maximum tolerated dose (MTD). The MTD was defined as the dose that caused \<1/3 of all participants treated with the study drug to experience a dose-limiting toxicity (DLT). A DLT was defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 3.0 Grade ≥3 nonhematological toxicity possibly or likely related to the study drug (except for nausea/vomiting/diarrhea without maximal symptomatic/prophylactic treatment); any CTCAE v 3.0 Grade ≥3 thrombocytopenia with bleeding; any CTCAE v3.0 Grade 4 hematological toxicity of \>5 days duration; any febrile neutropenia.
Time frame: Baseline, daily up to 21 days in Cycle 1
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2523355 | Recommended Dose for Phase 2 Studies | 4.0 mg/m²/day |
| LY2523355 + Pegfilgrastim | Recommended Dose for Phase 2 Studies | 6.0 mg/m²/day |
Secondary
Number of Participants With Clinically Significant Effects
Adverse events (AEs) were considered clinically significant effects. Data presented are the number of participants who experienced serious AEs (SAEs), other non-serious AEs and deaths during the study, including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline to study completion including 30-day follow-up up to 647 days,any AE reported
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY2523355 | Number of Participants With Clinically Significant Effects | AEs | 1 Participants |
| LY2523355 | Number of Participants With Clinically Significant Effects | SAEs | 0 Participants |
| LY2523355 | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| LY2523355 + Pegfilgrastim | Number of Participants With Clinically Significant Effects | AEs | 1 Participants |
| LY2523355 + Pegfilgrastim | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| LY2523355 + Pegfilgrastim | Number of Participants With Clinically Significant Effects | SAEs | 0 Participants |
| 0.5 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 0.5 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | AEs | 0 Participants |
| 0.5 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | SAEs | 0 Participants |
| 1.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | AEs | 2 Participants |
| 1.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | SAEs | 1 Participants |
| 1.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 2.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 2.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | SAEs | 0 Participants |
| 2.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | AEs | 3 Participants |
| 4.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | AEs | 13 Participants |
| 4.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | SAEs | 5 Participants |
| 4.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 5.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | SAEs | 3 Participants |
| 5.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | AEs | 5 Participants |
| 5.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 6.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | SAEs | 3 Participants |
| 6.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | AEs | 3 Participants |
| 6.0 mg/m²/Day LY | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 4.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 4.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | SAEs | 0 Participants |
| 4.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | AEs | 3 Participants |
| 6.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | SAEs | 11 Participants |
| 6.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | Death | 1 Participants |
| 6.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | AEs | 18 Participants |
| 7.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | Death | 0 Participants |
| 7.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | SAEs | 3 Participants |
| 7.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Clinically Significant Effects | AEs | 3 Participants |
Secondary
Number of Participants With Tumor Response
Data presented are the number of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions.
Time frame: Baseline to measured disease progression or discontinuation up to 617 days
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LY2523355 | Number of Participants With Tumor Response | 0 Participants |
| LY2523355 + Pegfilgrastim | Number of Participants With Tumor Response | 0 Participants |
| 0.5 mg/m²/Day LY | Number of Participants With Tumor Response | 0 Participants |
| 1.0 mg/m²/Day LY | Number of Participants With Tumor Response | 0 Participants |
| 2.0 mg/m²/Day LY | Number of Participants With Tumor Response | 0 Participants |
| 4.0 mg/m²/Day LY | Number of Participants With Tumor Response | 0 Participants |
| 5.0 mg/m²/Day LY | Number of Participants With Tumor Response | 1 Participants |
| 6.0 mg/m²/Day LY | Number of Participants With Tumor Response | 0 Participants |
| 4.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Tumor Response | 0 Participants |
| 6.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Tumor Response | 1 Participants |
| 7.0 mg/m²/Day LY + 6 mg PEG | Number of Participants With Tumor Response | 0 Participants |
Secondary
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose
AUC(0-∞) following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time frame: Cycle 1,Day 1(21-day cycle): End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime
Population: All enrolled participants who received 1 dose of LY2523355 on Day 1 of Cycle 1 with evaluable pharmacokinetic data to enable calculation of the LY2523355 AUC(0-∞) on Day 1 of Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | 81.8 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 33 |
| LY2523355 + Pegfilgrastim | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | 159 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 21 |
| 0.5 mg/m²/Day LY | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | 324 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 41 |
| 1.0 mg/m²/Day LY | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | 379 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 23 |
| 2.0 mg/m²/Day LY | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | 443 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 40 |
| 4.0 mg/m²/Day LY | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose | 642 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 50 |
Secondary
Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses
AUC(0-∞) following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time frame: Cycle 1, Day 3(21-day cycle): End of infusion
Population: All enrolled participants who received more than 1 dose of LY2523355 and had evaluable pharmacokinetic data to enable calculation of the LY2523355 AUC(0-∞) on Day 3 of Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 | Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | 109 ng*h/mL | Geometric Coefficient of Variation 19 |
| LY2523355 + Pegfilgrastim | Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | 220 ng*h/mL | Geometric Coefficient of Variation 30 |
| 0.5 mg/m²/Day LY | Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | 484 ng*h/mL | Geometric Coefficient of Variation 46 |
| 1.0 mg/m²/Day LY | Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | 593 ng*h/mL | Geometric Coefficient of Variation 45 |
| 2.0 mg/m²/Day LY | Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | 649 ng*h/mL | Geometric Coefficient of Variation 52 |
| 4.0 mg/m²/Day LY | Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses | 1090 ng*h/mL | Geometric Coefficient of Variation 54 |
Secondary
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose
Cmax following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time frame: Cycle 1 Day 1(21-day cycle):End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime
Population: All enrolled participants who received 1 dose of LY2523355 on Day 1 of Cycle 1 with evaluable pharmacokinetic data to enable determination of the LY2523355 plasma Cmax on Day 1 of Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | 32.6 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| LY2523355 + Pegfilgrastim | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | 61.7 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| 0.5 mg/m²/Day LY | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | 120 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| 1.0 mg/m²/Day LY | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | 127 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 2.0 mg/m²/Day LY | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | 168 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| 4.0 mg/m²/Day LY | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose | 222 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
Secondary
Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses
Cmax following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time frame: Cycle 1, Day 3(21-day cycle): End of infusion
Population: All enrolled participants who received more than 1 dose of LY2523355 and had evaluable pharmacokinetic data to enable determination of the LY2523355 Cmax on Day 3 of Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 | Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | 29.8 ng/mL | Geometric Coefficient of Variation 32 |
| LY2523355 + Pegfilgrastim | Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | 73.6 ng/mL | Geometric Coefficient of Variation 47 |
| 0.5 mg/m²/Day LY | Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | 126 ng/mL | Geometric Coefficient of Variation 49 |
| 1.0 mg/m²/Day LY | Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | 129 ng/mL | Geometric Coefficient of Variation 34 |
| 2.0 mg/m²/Day LY | Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | 193 ng/mL | Geometric Coefficient of Variation 37 |
| 4.0 mg/m²/Day LY | Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses | 231 ng/mL | Geometric Coefficient of Variation 23 |