A Study of LY2523355 in Participants With Breast Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01416389
• Collaborator: (none)
• Enrollment: 39
• Locations: 12
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the anti-tumor activity of LY2523355 relative to ixabepilone for the treatment of metastatic or locally recurrent breast cancer using change in tumor size as a continuous measure of response.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: LY2523355; Drug: ixabepilone; Drug: pegfilgrastim; Drug: filgrastim	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2 Study of LY2523355 Versus Ixabepilone in Patients With Metastatic or Locally Recurrent Breast Cancer Who Have Received Prior Taxane Therapy
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2523355 + pegfilgrastim or filgrastim LY2523355: Five milligrams per meter squared per day (mg/m^2/day) (dosage determined by calculating participant's body surface area) administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Pegfilgrastim or Filgrastim: Dosage is determined by standard of care and is administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Drug: LY2523355; Administered intravenously as a one hour infusion; Drug: pegfilgrastim; Administered intravenously; Drug: filgrastim; Administered intravenously
Active Comparator: ixabepilone Forty milligrams per meter squared per day (mg/m^2/day) (dosage determined by calculating participant's body surface area) administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Drug: ixabepilone; Administered intravenously

Outcome Measures

Primary Outcome Measures

1. Change in Tumor Size (CTS) From Baseline to the End of Cycle 2 [Baseline up to end of Cycle 2 (Day 42)]

   The log ratio of tumor size at Cycle 2 to tumor size at baseline is calculated for each participant, where the tumor size is the sum of the target lesion measurements at each assessment.

Secondary Outcome Measures

1. Percentage of Participants Achieving an Overall Response (Overall Response Rate) [Baseline to measured progressive disease or date of death from any cause (up to 423 days)]

   Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.

2. Progression-free Survival (PFS) [Baseline to measured progressive disease or date of death from any cause (up to 423 days)]

   Progression-free survival (PFS) is the time from the date of randomization to the first date of progressive disease (PD) or death due to any cause, whichever occurs first. PD is as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines, and is defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 millimeter (mm) (the appearance of 1 or more new lesions was considered progression). Kaplan-Meier analysis was performed on the observed distribution of PFS. Participants were censored from analysis for the following reasons: lack of disease assessment, lost to follow-up, and further anticancer therapy started. Median PFS is presented.

3. Percentage of Participants Achieving a Clinical Benefit (Clinical Benefit Rate) [Baseline to measured progressive disease or date of death from any cause (up to 423 days)]

   Clinical benefit rate is the proportion of participants who achieve a best response of complete response (CR), partial response (PR), or stable disease (SD) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with measurable disease, multiplied by 100.

4. Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 [Cycle 1: Day 1 and Day 3]

   Cmax is the maximum plasma concentration of LY2523355 after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1.

5. Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LSN2546307 [Cycle 1: Day 1 and Day 3]

   Cmax is the maximum plasma concentration of LSN2546307 (metabolite) after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1.

6. Pharmacokinetics, Intracycle Accumulation Ration (Ra) of LY2523355 [Cycle 1: Day 1 and Day 3]

   The intracycle accumulation ratio (Ra) is defined as the LY2523355 Cmax on Day 3 of Cycle 1 to the LY2523355 Cmax on Day 1 of Cycle 1 after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1.

Other Outcome Measures

1. Percentage of Deaths on Study Through the Follow-up Period [Baseline through end of treatment follow-up (up to 423 days)]

   The percentage of participants who died through the follow-up period of the study; the cause of death was not captured. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have histologic or cytologic diagnosis of metastatic or locally recurrent breast cancer that is not amenable to therapy given with curative intent.

• Have measurable disease defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 guidelines.

• Have received 2 or more prior standard cytotoxic chemotherapy regimens for metastatic breast cancer and be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Regimens received in the neoadjuvant or adjuvant setting are not counted as prior regimens.

• Have received a prior taxane in the neoadjuvant, adjuvant, or metastatic setting.

• Have recovered from the acute effects of prior chemotherapy, hormonal therapy, and radiation prior to study enrollment.

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

• Have adequate organ function.

Exclusion Criteria:

• Have Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater (moderate or worse) peripheral neuropathy

• Have a second primary malignancy.

• Have symptomatic, untreated, or uncontrolled central nervous system metastases.

• Have received autologous stem cell transplant following high-dose chemotherapy.

• Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in this study.

• Have active symptomatic fungal, bacterial, and/or known viral infection including active human immunodeficiency virus (HIV) or viral hepatitis.

• Have previously received LY2523355 in another study investigating this agent or therapy with ixabepilone or an ixabepilone-containing regimen.

• Have a history of radiation therapy involving more than 25 percent of the bone marrow.

• Have a Fridericia corrected QT (QTcF) interval of >470 milliseconds (msec) on screening electrocardiogram (ECG).

• Have QRS widening of >120 msec on screening ECG.

• Cannot change or stop taking a strong Cytochrome P450 3A4 (CYP3A4) inhibitor or CYP3A4 inducer per the ixabepilone label.

• Have hypersensitivity to drugs formulated with Cremophor® EL per the ixabepilone label.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Myers	Florida	United States	33916
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pensacola	Florida	United States	32503
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gainesville	Georgia	United States	30501
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bethesda	Maryland	United States	20817
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cincinnati	Ohio	United States	45219
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toledo	Ohio	United States	43623
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Columbia	South Carolina	United States	29210
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Spartanburg	South Carolina	United States	29303
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chattanooga	Tennessee	United States	37404
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nashville	Tennessee	United States	37203
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Worth	Texas	United States	76104
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Richmond	Virginia	United States	23230

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hour, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01416389
• Other Study ID Numbers: 12847; I1Y-MC-JFBE
• First Posted: Aug 15, 2011
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: Locally; Recurrent; Breast; Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Lenograstim

Study Results

Participant Flow

Pre-assignment Detail	Participants completed the study if they had at least 1 dose of study drug in Cycle 2 (or later) and had at least 1 post-baseline radiological tumor assessment or if the participant had a progression of disease or death. Non-completers were those that were lost to follow-up or who withdrew their consent to trial participation.

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis. Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
Period Title: Overall Study
STARTED	26	13
Received at Least 1 Dose of Study Drug	26	13
COMPLETED	23	13
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone	Total
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Total of all reporting groups
Overall Participants	26	13	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.3 (9.9)	57.8 (9.9)	60.8 (10)
Sex: Female, Male (Count of Participants)
Female	26 100%	13 100%	39 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	26 100%	13 100%	39 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 19.2%	4 30.8%	9 23.1%
White	21 80.8%	9 69.2%	30 76.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	13 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Change in Tumor Size (CTS) From Baseline to the End of Cycle 2
Description	The log ratio of tumor size at Cycle 2 to tumor size at baseline is calculated for each participant, where the tumor size is the sum of the target lesion measurements at each assessment.
Time Frame	Baseline up to end of Cycle 2 (Day 42)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication (LY2523355 or ixabepilone) and who had target lesion measurements at both baseline and the end of Cycle 2. One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis.

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
Measure Participants	17	11
Mean (Standard Deviation) [log ratio of end of Cycle 2 to baseline]	-0.0 (0.08)	-0.1 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2523355 + Pegfilgrastim or Filgrastim, Ixabepilone
	Comments	This measure is compared between two treatment arms using a one-sided t-test. This measure followed a normal distribution.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.344
	Comments
	Method	t-test, 1 sided
	Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving an Overall Response (Overall Response Rate)
Description	Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.
Time Frame	Baseline to measured progressive disease or date of death from any cause (up to 423 days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication (LY2523355 or ixabepilone). One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis.

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
Measure Participants	26	13
Number (90% Confidence Interval) [percentage of responders]	3.8	7.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2523355 + Pegfilgrastim or Filgrastim, Ixabepilone
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival (PFS) is the time from the date of randomization to the first date of progressive disease (PD) or death due to any cause, whichever occurs first. PD is as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines, and is defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 millimeter (mm) (the appearance of 1 or more new lesions was considered progression). Kaplan-Meier analysis was performed on the observed distribution of PFS. Participants were censored from analysis for the following reasons: lack of disease assessment, lost to follow-up, and further anticancer therapy started. Median PFS is presented.
Time Frame	Baseline to measured progressive disease or date of death from any cause (up to 423 days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication (LY2523355 or ixabepilone). The total number of participants censored is 7. One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis.

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
Measure Participants	22	10
Median (90% Confidence Interval) [months]	1.71	2.76

4. Secondary Outcome

Title	Percentage of Participants Achieving a Clinical Benefit (Clinical Benefit Rate)
Description	Clinical benefit rate is the proportion of participants who achieve a best response of complete response (CR), partial response (PR), or stable disease (SD) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with measurable disease, multiplied by 100.
Time Frame	Baseline to measured progressive disease or date of death from any cause (up to 423 days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication (LY2523355 or ixabepilone). One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis.

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
Measure Participants	26	13
Number (90% Confidence Interval) [percentage of responders]	46.2	61.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2523355 + Pegfilgrastim or Filgrastim, Ixabepilone
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.365
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355
Description	Cmax is the maximum plasma concentration of LY2523355 after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1.
Time Frame	Cycle 1: Day 1 and Day 3

Outcome Measure Data

Analysis Population Description

Participants who received 1 dose of LY2523355 on Day 1 and Day 3 of Cycle 1 and who have evaluable pharmacokinetic data to enable estimation of the LY2523355 Cmax on Day 1 and Day 3 of Cycle 1. One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2, and is not included in this analysis.

Arm/Group Title	LY2523355
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]).
Measure Participants	24
Cycle 1, Day 1	161 (81)
Cycle 1, Day 3	150 (56)

6. Other Pre-specified Outcome

Title	Percentage of Deaths on Study Through the Follow-up Period
Description	The percentage of participants who died through the follow-up period of the study; the cause of death was not captured. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Baseline through end of treatment follow-up (up to 423 days)

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication (LY2523355 or ixabepilone). One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis.

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim	Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.	Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
Measure Participants	26	13
Number [percentage of participants]	7.7 29.6%	15.4 118.5%

7. Secondary Outcome

Title	Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LSN2546307
Description	Cmax is the maximum plasma concentration of LSN2546307 (metabolite) after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1.
Time Frame	Cycle 1: Day 1 and Day 3

Outcome Measure Data

Analysis Population Description

Participants who received 1 dose of LY2523355 on Day 1 and Day 3 of Cycle 1 and who have evaluable pharmacokinetic data to enable estimation of the LSN2546307 Cmax on Day 1 and Day 3 of Cycle 1.One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2, and is not included in this analysis.

Arm/Group Title	LSN2546307
Arm/Group Description	LSN2546307 is the metabolite of LY2523355. LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]).
Measure Participants	24
Cycle 1, Day 1	5.08 (57)
Cycle1, Day 3	5.53 (67)

8. Secondary Outcome

Title	Pharmacokinetics, Intracycle Accumulation Ration (Ra) of LY2523355
Description	The intracycle accumulation ratio (Ra) is defined as the LY2523355 Cmax on Day 3 of Cycle 1 to the LY2523355 Cmax on Day 1 of Cycle 1 after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1.
Time Frame	Cycle 1: Day 1 and Day 3

Outcome Measure Data

Analysis Population Description

Participants who received 1-dose of LY2523355 on Day 1 and Day 3 of Cycle 1 and who have evaluable pharmacokinetic data to enable estimation of the LY2523355 Cmax on Day 1 and Day 3 of Cycle 1. One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2, and is not included in this analysis.

Arm/Group Title	LY2523355
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]).
Measure Participants	21
Geometric Mean (Geometric Coefficient of Variation) [unitless ratio]	0.92 (77)

Adverse Events

Arm/Group Title	LY2523355 + Pegfilgrastim or Filgrastim		Ixabepilone
Arm/Group Description	LY2523355 administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (5 milligrams per meter squared per day [mg/m^2/day]). One participant was mistakenly dosed with 6 mg/m^2/day in Cycle 1 and for 2 doses in Cycle 2. The dose was subsequently corrected and the participant is included in this analysis. Pegfilgrastim or filgrastim administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. Dosage is determined by standard of care. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.		Ixabepilone administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. Dosage determined by calculating participant's body surface area (40 mg/m^2). If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met.
All Cause Mortality
	LY2523355 + Pegfilgrastim or Filgrastim		Ixabepilone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2523355 + Pegfilgrastim or Filgrastim		Ixabepilone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/26 (19.2%)		4/13 (30.8%)
Blood and lymphatic system disorders
Febrile neutropenia	1/26 (3.8%)	1	1/13 (7.7%)	1
Gastrointestinal disorders
Abdominal pain	0/26 (0%)	0	1/13 (7.7%)	1
Constipation	0/26 (0%)	0	1/13 (7.7%)	1
Nausea	1/26 (3.8%)	1	0/13 (0%)	0
Pancreatitis	1/26 (3.8%)	1	0/13 (0%)	0
Vomiting	2/26 (7.7%)	2	0/13 (0%)	0
General disorders
Pain	0/26 (0%)	0	1/13 (7.7%)	1
Infections and infestations
Pneumonia	0/26 (0%)	0	1/13 (7.7%)	1
Urinary tract infection	1/26 (3.8%)	1	0/13 (0%)	0
Injury, poisoning and procedural complications
Lumbar vertebral fracture	1/26 (3.8%)	1	0/13 (0%)	0
Investigations
Ammonia increased	1/26 (3.8%)	1	0/13 (0%)	0
Nervous system disorders
Hepatic encephalopathy	1/26 (3.8%)	1	0/13 (0%)	0
Other (Not Including Serious) Adverse Events
	LY2523355 + Pegfilgrastim or Filgrastim		Ixabepilone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		12/13 (92.3%)
Blood and lymphatic system disorders
Anaemia	8/26 (30.8%)	8	1/13 (7.7%)	1
Leukopenia	3/26 (11.5%)	3	1/13 (7.7%)	1
Lymphopenia	1/26 (3.8%)	1	1/13 (7.7%)	1
Neutropenia	6/26 (23.1%)	6	1/13 (7.7%)	1
Thrombocytopenia	3/26 (11.5%)	3	2/13 (15.4%)	2
Eye disorders
Lacrimation increased	2/26 (7.7%)	2	0/13 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/26 (0%)	0	1/13 (7.7%)	1
Bowel movement irregularity	0/26 (0%)	0	1/13 (7.7%)	1
Constipation	3/26 (11.5%)	3	3/13 (23.1%)	3
Diarrhoea	2/26 (7.7%)	2	3/13 (23.1%)	3
Dry mouth	0/26 (0%)	0	1/13 (7.7%)	1
Nausea	8/26 (30.8%)	8	5/13 (38.5%)	5
Oral disorder	0/26 (0%)	0	1/13 (7.7%)	1
Oral pain	2/26 (7.7%)	2	1/13 (7.7%)	1
Stomatitis	4/26 (15.4%)	4	0/13 (0%)	0
Vomiting	2/26 (7.7%)	2	3/13 (23.1%)	3
General disorders
Asthenia	0/26 (0%)	0	1/13 (7.7%)	1
Chills	0/26 (0%)	0	1/13 (7.7%)	1
Device malfunction	0/26 (0%)	0	1/13 (7.7%)	1
Fatigue	13/26 (50%)	13	5/13 (38.5%)	5
Mucosal inflammation	1/26 (3.8%)	1	2/13 (15.4%)	2
Oedema	0/26 (0%)	0	1/13 (7.7%)	1
Oedema peripheral	3/26 (11.5%)	3	0/13 (0%)	0
Pain	2/26 (7.7%)	2	1/13 (7.7%)	1
Pyrexia	2/26 (7.7%)	2	0/13 (0%)	0
Immune system disorders
Hypersensitivity	1/26 (3.8%)	1	1/13 (7.7%)	1
Infections and infestations
Herpes zoster	0/26 (0%)	0	1/13 (7.7%)	1
Investigations
Blood alkaline phosphatase increased	1/26 (3.8%)	1	1/13 (7.7%)	1
Blood bilirubin decreased	0/26 (0%)	0	1/13 (7.7%)	1
Globulins decreased	0/26 (0%)	0	1/13 (7.7%)	1
Platelet count decreased	1/26 (3.8%)	1	1/13 (7.7%)	1
Weight decreased	1/26 (3.8%)	1	1/13 (7.7%)	1
White blood cell count decreased	3/26 (11.5%)	3	0/13 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	6/26 (23.1%)	6	0/13 (0%)	0
Dehydration	1/26 (3.8%)	1	3/13 (23.1%)	3
Hyperglycaemia	1/26 (3.8%)	1	1/13 (7.7%)	1
Hyperkalaemia	0/26 (0%)	0	1/13 (7.7%)	1
Hyperphosphataemia	0/26 (0%)	0	1/13 (7.7%)	1
Hypocalcaemia	2/26 (7.7%)	2	1/13 (7.7%)	1
Hypokalaemia	3/26 (11.5%)	3	1/13 (7.7%)	1
Hypophagia	0/26 (0%)	0	1/13 (7.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/26 (7.7%)	2	5/13 (38.5%)	5
Back pain	3/26 (11.5%)	3	0/13 (0%)	0
Bone pain	1/26 (3.8%)	1	3/13 (23.1%)	3
Myalgia	2/26 (7.7%)	2	2/13 (15.4%)	2
Pain in extremity	1/26 (3.8%)	1	1/13 (7.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/26 (3.8%)	1	1/13 (7.7%)	1
Nervous system disorders
Dizziness	3/26 (11.5%)	3	0/13 (0%)	0
Dizziness postural	0/26 (0%)	0	1/13 (7.7%)	1
Dysgeusia	3/26 (11.5%)	3	1/13 (7.7%)	1
Headache	2/26 (7.7%)	2	2/13 (15.4%)	2
Neuropathy peripheral	0/26 (0%)	0	4/13 (30.8%)	4
Paraesthesia	1/26 (3.8%)	1	1/13 (7.7%)	1
Parosmia	0/26 (0%)	0	1/13 (7.7%)	1
Peripheral sensory neuropathy	1/26 (3.8%)	1	3/13 (23.1%)	3
Tremor	0/26 (0%)	0	1/13 (7.7%)	1
Psychiatric disorders
Anxiety	0/26 (0%)	0	1/13 (7.7%)	1
Insomnia	3/26 (11.5%)	3	2/13 (15.4%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/26 (15.4%)	4	2/13 (15.4%)	2
Dyspnoea	5/26 (19.2%)	5	2/13 (15.4%)	2
Pleural effusion	0/26 (0%)	0	1/13 (7.7%)	1
Pneumonitis	0/26 (0%)	0	1/13 (7.7%)	1
Wheezing	1/26 (3.8%)	1	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/26 (3.8%)	1	1/13 (7.7%)	1
Skin ulcer	0/26 (0%)	0	1/13 (7.7%)	1
Vascular disorders
Hot flush	1/26 (3.8%)	1	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.