LY2523355 administered intravenously on Days 1, 5 and 9, starting dose is 2 milligrams per meter squared (mg/m\^2) for 2 planned 21-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met.

LY2523355 administered intravenously on Days 1 and 8, starting dose is 8 mg/m\^2 for 2 planned 21-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met.

LY2523355 administered intravenously on Days 1 and 5, starting dose is 8 mg/m\^2 for 2 planned 21-day cycles and 6 mg pegfilgrastim administered subcutaneously on Day 6 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met.

LY2523355 administered on Days 1 and 4, starting dose is 12 mg/m\^2 for 2 planned 21-day cycles and 6 mg pegfilgrastim administered subcutaneously on Day 5 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion are met.

pegfilgrastim

LY2523355

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

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).

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.

A Dose-Escalation Study for Patients With Advanced Cancer

A Phase 1 Dose-Escalation Study of LY2523355 in Patients With Advanced Cancer

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.

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.

Plasma Cmax following a single dose of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).

Plasma Cmax following multiple doses of LY2523355 at each dose level across all schedules and in the presence or absence of pegfilgrastim (PEG).

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).

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).

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.

Eli Lilly and Company

Part A (Dose Escalation Phase): 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.

Part A - Days 1, 5, 9 - 2 mg/m^2/Day

Part A (Dose Escalation Phase): 4 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

Part A - Days 1, 5, 9 - 4 mg/m^2/Day

Part A (Dose Escalation Phase): 8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

Part A - Days 1, 5, 9 - 8 mg/m^2/Day

Part A (Dose Escalation Phase): 7 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

Part A - Days 1, 5, 9 - 7 mg/m^2/Day

Part A (Dose Escalation Phase): 6 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

Part A - Days 1, 5, 9 - 6 mg/m^2/Day

Part A (Dose Escalation Phase): 5 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

Part A - Days 1, 5, 9 - 5 mg/m^2/Day

Part A (Dose Escalation Phase): 8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 8 of 21-day cycle.

Part A - Days 1, 8 - 8 mg/m^2/Day

Part A (Dose Escalation Phase): 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.

Part A - Days 1, 5+PEG - 8 mg/m^2/Day

Part A (Dose Escalation Phase): 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.

Part A - Days 1, 5+PEG - 12 mg/m^2/Day

Part A (Dose Escalation Phase): 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.

Part A - Days 1, 5+PEG - 16 mg/m^2/Day

Part A (Dose Escalation Phase): 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.

Part A - Days 1, 5+PEG - 14 mg/m^2/Day

Part B (Dose Maintenance Phase): 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.

Part B - Days 1, 5+PEG - 12 mg/m^2/Day

Part B (Dose Maintenance Phase): 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 Day 5.

Part B - Days 1, 4+PEG - 12 mg/m^2/d

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.

4 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

7 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

6 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

5 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5, and 9 of 21-day cycle.

8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 8 of 21-day cycle.

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.

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.

Part A and B - Days 1, 5+PEG - 12 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.

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.

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.

Part B - Days 1, 4+PEG - 12 mg/m^2/Day

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

All participants who received at least 1 dose of LY2523355.

Chief Medical Officer

Escalating doses starting at 2 milligrams per meter squared per day (mg/m\^2/day) LY2523355 administered by intravenous infusion over 1 hour on Days 1, 5, and 9; escalating doses starting at 8 mg/m\^2/day LY2523355 administered by intravenous infusion over 1 hour on Days 1 and 8 or Days 1 and 5 plus 6 mg pegfilgrastim (PEG) administered subcutaneously on Day 6; or 12 mg/m\^2/day LY2523355 administered by intravenous infusion over 1 hour on Days 1 and 4 plus 6 mg PEG administered subcutaneously on Day 5 of 21-day cycle for 2 planned cycles and any subsequent cycle up to 38 cycles of 21-days. The maximum allowed dose was 30 mg/m\^2/day.

LY2523355 / LY2523355 +PEG

Recommended Dose and Schedule for Phase 2 Studies

Serious AEs

Other Non-Serious AEs

Part A - Days 1, 5+PEG - 8 mg/m2/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.

All participants who had at least 1 dose of LY2523355.

Number of Participants With Clinically Significant Effects

2 mg/m^2/Day LY2523355

4 mg/m^2/Day LY2523355

5 mg/m^2/Day LY2523355

6 mg/m^2/Day LY2523355

7 mg/m^2/Day LY2523355

8 mg/m\^2/day LY2523355 administered intravenously as a 1-hour infusion across all schedules and in the presence or absence of PEG administered subcutaneously.

8 mg/m^2/Day LY2523355

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 and on Days 1 and 4 of 21-day cycle plus PEG administered subcutaneously on Day 5.

12 mg/m^2/Day LY2523355

14 mg/m^2/Day LY2523355

16 mg/m^2/Day LY2523355

All participants who received 1 dose of LY2523355 and had Cmax samples collected on Day 1 of Cycle 1.

Pharmacokinetics Maximum Concentration (Cmax), Single Dose

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.

Pharmacokinetics Maximum Concentration (Cmax), Multiple Dose

AUC(0-∞)

AUC(0-24)

5 mg/m^2/Day LY25233552

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).

Pharmacokinetics Area Under the Concentration-time Curve (AUC), Single Dose

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.

Pharmacokinetic Areas Under the Concentration Time Curve (AUC), Multiple Dose

Escalating dose started at 2 milligrams per meter squared (mg/m\^2) LY2523355 administered intravenously as a 1-hour infusion on Days 1, 5 and 9, for two planned cycles of 21 days. Dose could be escalated by a maximum increment of the lesser of doubling the current dose or 4 milligrams per meter squared per day (mg/m\^2/day), with a maximum allowed dose of 30 mg/m\^2/day. Participants continued on study drug until disease progression, unacceptable toxicity or other withdrawal criterion were met up to 38 cycles of 21 days.

LY2523355 Days 1, 5 and 9

Escalating dose started at 8 mg/m\^2 of LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 8 for two planned 21-day cycles. Dose could be escalated by a maximum of 4 mg/m\^2/day, with a maximum allowed dose of 30 mg/m\^2/day. Participants continued on study drug until disease progression, unacceptable toxicity or other withdrawal criterion were met up to 38 cycles of 21-days.

LY2523355 Days 1 and 8

Escalating dose started at 8 mg/m\^2 LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 5, for two planned cycles of 21-days and 6 mg pegfilgrastim (PEG) administered subcutaneously on Day 6 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received. Dose could be escalated by a maximum of 4 mg/m\^2/day, with a maximum allowed dose of 30 mg/m\^2/day. Participants continued on study drug until disease progression, unacceptable toxicity or other withdrawal criterion were met up to 38 cycles of 21-days.

LY2523355 Days 1 and 5 + PEG

12 mg/m\^2 LY2523355 administered intravenously as a 1-hour infusion on Days 1 and 4, for two planned 21 days cycles, 6 mg PEG administered subcutaneously on Day 5 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received. Participants continued on study drug until disease progression, unacceptable toxicity or other withdrawal criterion were met up to 38 cycles of 21-days.

Spots Global Cancer Trial Database for A Dose-Escalation Study for Patients With Advanced Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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