Advanced Cancer
Conditions
Keywords
Advanced 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 patients with advanced and/or metastatic cancer (including non-Hodgkin's lymphoma) for whom no treatment of higher priority exists.
Interventions
DRUGpegfilgrastim
Administered subcutaneously
DRUGLY2523355
Administered intravenously
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 the dose confirmation phase (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) or Revised International Working Group Lymphoma Response Criteria * 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 * Females who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose and Schedule for Phase 2 Studies | Cycle 1 (21 days): Day 1, 5 and 9, any AE reported | The recommended dose and schedule for Phase 2 studies is defined as the maximum tolerated dose (MTD). MTD is defined as the dose level at which no more than 2 dose limiting toxicities (DLTs), no more than 3 dose reductions (DR) or dose omissions (DO) and no more than 1 DLT plus 2 DR/DO occurred. DLT is defined as an adverse event (AE) occurring in Cycle 1 with the following criteria according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0: Any ≥Grade 3 nonhematological toxicity (except nausea/vomiting or diarrhea controlled with treatment or fatigue); ≥Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding; Grade 4 hematological toxicity of \>5 days duration, excluding thrombocytopenia; febrile neutropenia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Maximum Concentration (Cmax), Single Dose | Cycle 1 Day 1 of 21-day cycle: Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | Plasma Cmax following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). |
| Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | Plasma Cmax following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). |
| Number of Participants With Clinically Significant Effects | Baseline to Cycle 38 (21-day cycles): daily for AEs | Clinically significant effects were defined as serious and other non-serious adverse events (AEs). A summary of serious and other non-serious AEs is located in the Reported Adverse Events module. |
| Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | Plasma AUC from time zero to infinity (0-∞) and AUC from time zero to 24 hours (0-24) post-dose following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). |
| Number of Participants With Tumor Response | Baseline to measured disease progression or discontinuation up to Cycle 38 (21-day cycles) | Response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and the Revised International Working Group (IWG) lymphoma response criteria for lymphoma patients. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Tumor response is CR + PR. |
| Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose | Plasma AUC from time zero to infinity \[AUC(0-∞)\] and AUC from time zero to 24 hours post-dose \[AUC(0-24)\] following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG). |
Countries
United States
Participant flow
Pre-assignment details
Part A is the LY2523355 dose escalation phase and Part B is the LY2523355 dose confirmation phase. The reasons for discontinuation listed in the participant flow are the reasons the participant discontinued treatment and a participant was considered to have completed the trial if they received at 2 cycles of treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part A - Days 1, 5, 9 - 2 mg/m^2/Day 2 milligrams per meter squared per day (mg/m\^2/day) LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle. | 3 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day 4 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle. | 3 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day 8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle. | 6 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day 7 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle. | 6 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day 6 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle. | 6 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day 5 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle. | 3 |
| Part A - Days 1, 8 - 8 mg/m^2/Day 8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 8 of 21-day cycle. | 6 |
| Part A - Days 1, 5+PEG - 8 mg/m^2/Day 8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 5 of 21-day cycle plus pegfilgrastim (PEG) administered subcutaneously on Day 6. | 3 |
| Part A and B - Days 1, 5+PEG - 12 mg/m^2/Day 12 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 5 of 21-day cycle plus PEG administered subcutaneously on Day 6 in Part A and Part B. | 13 |
| Part A - Days 1, 5+PEG - 16 mg/m^2/Day 16 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 5 of 21-day cycle plus PEG administered subcutaneously on Day 6. | 4 |
| Part A - Days 1, 5+PEG - 14 mg/m^2/Day 14 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 5 of 21-day cycle plus PEG administered subcutaneously on Day 6. | 4 |
| Part B - Days 1, 4+PEG - 12 mg/m^2/Day 12 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 4 of 21-day cycle plus PEG administered subcutaneously on Day 5. | 6 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Progressive Disease | 3 | 2 | 3 | 5 | 5 | 3 | 5 | 3 | 10 | 2 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A - Days 1, 5, 9 - 2 mg/m^2/Day | Total | Part B - Days 1, 4+PEG - 12 mg/m^2/Day | Part A - Days 1, 5+PEG - 14 mg/m^2/Day | Part A - Days 1, 5+PEG - 16 mg/m^2/Day | Part A and B - Days 1, 5+PEG - 12 mg/m^2/Day | Part A - Days 1, 5+PEG - 8 mg/m^2/Day | Part A - Days 1, 8 - 8 mg/m^2/Day | Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Part A - Days 1, 5, 9 - 4 mg/m^2/Day |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.60 years STANDARD_DEVIATION 5.484 | 60.08 years STANDARD_DEVIATION 11.471 | 59.43 years STANDARD_DEVIATION 18.595 | 60.18 years STANDARD_DEVIATION 10.205 | 57.10 years STANDARD_DEVIATION 25.069 | 62.02 years STANDARD_DEVIATION 7.598 | 67.10 years STANDARD_DEVIATION 1.212 | 59.77 years STANDARD_DEVIATION 6.959 | 56.73 years STANDARD_DEVIATION 7.267 | 58.45 years STANDARD_DEVIATION 12.425 | 61.67 years STANDARD_DEVIATION 9.352 | 59.73 years STANDARD_DEVIATION 7.541 | 48.07 years STANDARD_DEVIATION 19.657 |
| Race/Ethnicity, Customized African | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 1 Participants | 51 Participants | 6 Participants | 3 Participants | 4 Participants | 10 Participants | 3 Participants | 6 Participants | 3 Participants | 4 Participants | 6 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized West Asian (Indian sub-continent) | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 63 participants | 6 participants | 4 participants | 4 participants | 13 participants | 3 participants | 6 participants | 3 participants | 6 participants | 6 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 30 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 33 Participants | 4 Participants | 1 Participants | 2 Participants | 9 Participants | 1 Participants | 4 Participants | 0 Participants | 2 Participants | 5 Participants | 2 Participants | 2 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 | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 6 / 6 | 6 / 6 | 6 / 6 | 3 / 3 | 6 / 6 | 3 / 3 | 3 / 3 | 4 / 4 | 4 / 4 | 10 / 10 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 2 / 6 | 2 / 6 | 1 / 6 | 0 / 3 | 1 / 6 | 0 / 3 | 0 / 3 | 3 / 4 | 2 / 4 | 4 / 10 | 4 / 6 |
Outcome results
Primary
Recommended Dose and Schedule for Phase 2 Studies
The recommended dose and schedule for Phase 2 studies is defined as the maximum tolerated dose (MTD). MTD is defined as the dose level at which no more than 2 dose limiting toxicities (DLTs), no more than 3 dose reductions (DR) or dose omissions (DO) and no more than 1 DLT plus 2 DR/DO occurred. DLT is defined as an adverse event (AE) occurring in Cycle 1 with the following criteria according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0: Any ≥Grade 3 nonhematological toxicity (except nausea/vomiting or diarrhea controlled with treatment or fatigue); ≥Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding; Grade 4 hematological toxicity of \>5 days duration, excluding thrombocytopenia; febrile neutropenia.
Time frame: Cycle 1 (21 days): Day 1, 5 and 9, any AE reported
Population: All participants who received at least 1 dose of LY2523355.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2523355 / LY2523355 +PEG | Recommended Dose and Schedule for Phase 2 Studies | 8 mg/m^2/day |
Secondary
Number of Participants With Clinically Significant Effects
Clinically significant effects were defined as serious and other non-serious adverse events (AEs). A summary of serious and other non-serious AEs is located in the Reported Adverse Events module.
Time frame: Baseline to Cycle 38 (21-day cycles): daily for AEs
Population: All participants who had at least 1 dose of LY2523355.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY2523355 / LY2523355 +PEG | Number of Participants With Clinically Significant Effects | Serious AEs | 1 Participants |
| LY2523355 / LY2523355 +PEG | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 3 Participants |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 2 Participants |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 2 Participants |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 2 Participants |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 6 Participants |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 2 Participants |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 6 Participants |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 6 Participants |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 1 Participants |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 3 Participants |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 0 Participants |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 1 Participants |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 6 Participants |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 0 Participants |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 3 Participants |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 0 Participants |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 3 Participants |
| Part A - Days 1, 5+PEG - 16 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 4 Participants |
| Part A - Days 1, 5+PEG - 16 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 3 Participants |
| Part A - Days 1, 5+PEG - 14 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 4 Participants |
| Part A - Days 1, 5+PEG - 14 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 2 Participants |
| Part B - Days 1, 5+PEG - 12 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Serious AEs | 4 Participants |
| Part B - Days 1, 5+PEG - 12 mg/m^2/Day | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 10 Participants |
| Part B - Days 1, 4+PEG - 12 mg/m^2/d | Number of Participants With Clinically Significant Effects | Other Non-Serious AEs | 6 Participants |
| Part B - Days 1, 4+PEG - 12 mg/m^2/d | Number of Participants With Clinically Significant Effects | Serious AEs | 4 Participants |
Secondary
Number of Participants With Tumor Response
Response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and the Revised International Working Group (IWG) lymphoma response criteria for lymphoma patients. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Tumor response is CR + PR.
Time frame: Baseline to measured disease progression or discontinuation up to Cycle 38 (21-day cycles)
Population: All participants who received 1 dose of LY2523355.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2523355 / LY2523355 +PEG | Number of Participants With Tumor Response | 0 participants |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Number of Participants With Tumor Response | 0 participants |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Number of Participants With Tumor Response | 0 participants |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Number of Participants With Tumor Response | 0 participants |
Secondary
Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose
Plasma AUC from time zero to infinity (0-∞) and AUC from time zero to 24 hours (0-24) post-dose following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).
Time frame: Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose
Population: All participants who received 2 doses of study drug and had pharmacokinetic samples collected on Day 4, 5, 8, or 9 of Cycle 1 (based on schedule of administration) to enable calculation of AUC(0-∞) and AUC(0-24) after multiple dose administration of LY2523355.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2523355 / LY2523355 +PEG | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 172 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| LY2523355 / LY2523355 +PEG | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 130 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 377 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 73 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 308 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 77 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 718 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 508 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 356 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 298 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 717 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 562 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 452 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 575 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 956 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 1340 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 1280 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 1110 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46 |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-∞) | 1510 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36 |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose | AUC(0-24) | 1230 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
Secondary
Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose
Plasma AUC from time zero to infinity \[AUC(0-∞)\] and AUC from time zero to 24 hours post-dose \[AUC(0-24)\] following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).
Time frame: Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose
Population: All participants who received 1 dose of LY2523355 and had pharmacokinetic samples collected on Day 1 of Cycle 1 to enable calculation of AUC(0-∞) and AUC(0-24).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2523355 / LY2523355 +PEG | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 158 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 55 |
| LY2523355 / LY2523355 +PEG | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 106 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 47 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 517 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 71 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 351 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 63 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 584 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 70 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 366 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 57 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 648 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 45 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 507 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 758 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 566 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 513 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 669 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 1040 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 1400 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 2050 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 1620 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-∞) | 1900 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose | AUC(0-24) | 1400 nanograms*hour/milliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
Secondary
Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose
Plasma Cmax following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).
Time frame: Cycle 1 Days 4, 5, 8 or 9 of 21-day cycle:Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose
Population: All participants who received 2 doses of study drug and had a Cmax sample collected on Days 4, 5, 8 or 9 of Cycle 1 (based on schedule of administration) after multiple dose administration of LY2523355.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 / LY2523355 +PEG | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 49.1 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 121 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 196 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 43 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 124 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 200 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 69 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 186 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 367 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 415 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 46 |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose | 485 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
Secondary
Pharmacokinetics Maximum Concentration (Cmax), Single Dose
Plasma Cmax following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).
Time frame: Cycle 1 Day 1 of 21-day cycle: Predose, 1 hour (hr), 2,4,6,8,24,48 and 72 hr postdose
Population: All participants who received 1 dose of LY2523355 and had Cmax samples collected on Day 1 of Cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 / LY2523355 +PEG | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 45.2 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Part A - Days 1, 5, 9 - 4 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 126 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Part A - Days 1, 5, 9 - 8 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 137 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 81 |
| Part A - Days 1, 5, 9 - 7 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 196 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Part A - Days 1, 5, 9 - 6 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 218 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Part A - Days 1, 5, 9 - 5 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 192 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Part A - Days 1, 8 - 8 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 379 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| Part A - Days 1, 5+PEG - 8 mg/m2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 598 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Part A - Days 1, 5+PEG - 12 mg/m^2/Day | Pharmacokinetics Maximum Concentration (Cmax), Single Dose | 463 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 43 |