A Study of Abemaciclib (LY2835219) Alone or in Combination With Other Agents in Participants With Previously Treated Pancreatic Ductal Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT02981342
• Recruitment Status: Completed
• First Posted: December 5, 2016
• Results First Posted: June 25, 2019
• Last Update Posted: November 20, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: Abemaciclib; Drug: LY3023414; Drug: Gemcitabine; Drug: Capecitabine
• Enrollment: 106

Participant Flow

Recruitment Details	Study was planned for stage 1 & stage 2. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1. Completed participants are those who has CR, PR, SD, or PD and is off treatment.
Pre-assignment Details	Per protocol, no efficacy analysis was planned for safety lead in. Purpose of safety lead in was only safety evaluation. All efficacy was done on randomized pts.

Arm/Group Title	150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in)	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description	Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle.	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Period Title: Overall Study
Started	7	33	33	33
Received at Least One Dose of Study Drug	7	32	33	26
Completed	7	22	20	19
Not Completed	0	11	13	14
Reason Not Completed
Adverse Event	0	0	0	1
Death	0	9	9	4
Withdrawal by Subject	0	0	3	1
Study closed by sponsor	0	0	1	1
Randomized, Never Treated	0	1	0	7
Lost to Follow-up	0	1	0	0

Baseline Characteristics

Arm/Group Title		150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in)	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine	Total
Arm/Group Description		Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle.	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		7	33	33	33	106
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	7 participants	32 participants	33 participants	26 participants	98 participants
		65.29 (6.99)	61.09 (7.83)	62.52 (8.97)	66.85 (7.61)	63.40 (8.34)
		[1] Measure Analysis Population Description: All randomized participants who received at least one dose of study drug.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
	Female	4	18	16	19	57
	Male	3	15	17	14	49
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
	Hispanic or Latino	0	2	4	3	9
	Not Hispanic or Latino	7	30	28	24	89
	Unknown or Not Reported	0	1	1	6	8
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
	American Indian or Alaska Native	0	0	0	0	0
	Asian	0	7	5	4	16
	Native Hawaiian or Other Pacific Islander	0	0	0	0	0
	Black or African American	0	0	1	3	4
	White	7	26	26	25	84
	More than one race	0	0	0	0	0
	Unknown or Not Reported	0	0	1	1	2
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
Belgium	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	8	6	5	19
United States	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		7	8	10	8	33
Taiwan	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	7	4	3	14
United Kingdom	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	1	0	0	1
Israel	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	2	4	5	11
Australia	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	1	1	3	5
France	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	1	1	6	8
Spain	Number Analyzed	7 participants	33 participants	33 participants	33 participants	106 participants
		0	5	7	3	15

Outcome Measures

1. Primary Outcome

Title	Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
Description	Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time Frame	Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	33	33	33
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of Participants
	15.2; (2.9 to 27.4)	12.1; (1.0 to 23.3)	36.4; (20 to 52.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0495
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0230
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

2. Primary Outcome

Title	Stage 2: Progression Free Survival (PFS)
Description	PFS was defined as the time from the date of randomization until first observation of objective progressive disease as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a patient does not have a complete baseline disease assessment, then the PFS time will be censored at the randomization date, regardless of whether or not objectively determined disease progression or death has been observed for the patient; otherwise, if a patient is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time will be censored at the last complete objective progression-free disease assessment date.
Time Frame	Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Abemaciclib 200 mg: 3, Abemaciclib 150mg + LY3023414 150mg: 8, Gemcitabine & Capecitabine: 18; No participants were enrolled in stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled in stage 1.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	33	33	33
Median (95% Confidence Interval); Unit of Measure: Months
	1.68; (1.35 to 1.84)	1.81; (1.28 to 1.91)	3.25; (1.05 to 5.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0085
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0123
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

3. Secondary Outcome

Title	Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR
Description	Objective response rate (ORR) is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
Time Frame	Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	33	33	33
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of Participants
	3; (0 to 8.9)	0 [1]; (NA to NA)	3; (0 to 8.9)

[1]

Data did not allow it to be estimable.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3017
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

4. Secondary Outcome

Title	Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20))
Description	Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax).
Time Frame	Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of Abemaciclib along with Galunisertib and had evaluable PK samples.

Arm/Group Title	150mg Abemaciclib + 150mg Galunisertib
Arm/Group Description:	Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle.
Overall Number of Participants Analyzed	4
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nanogram per Millilitre (ng/mL)
Abemaciclib	356; (137%)
LSN2839567 (M2)	85.1; (66%)
LSN3106726 (M20)	153; (58%)

5. Secondary Outcome

Title	Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414
Description	[Not Specified]
Time Frame	Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)

Outcome Measure Data

Analysis Population Description

Zero Participants Analyzed: AUC cannot be calculated due to insufficient data collected.

Arm/Group Title	150mg Abemaciclib + 150mg LY3023414
Arm/Group Description:	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

6. Secondary Outcome

Title	Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414
Description	[Not Specified]
Time Frame	Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)

Outcome Measure Data

Analysis Population Description

Zero Participants Analyzed: Cmax cannot be calculated due to insufficient data collected.

Arm/Group Title	150mg Abemaciclib + 150mg LY3023414
Arm/Group Description:	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

7. Secondary Outcome

Title	Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD
Description	[Not Specified]
Time Frame	Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)

Outcome Measure Data

Analysis Population Description

Data not reported, no patients were enrolled to stage 2.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months
Description	Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD ≥6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time Frame	Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	33	33	33
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	3; (0 to 8.9)	0; (0 to 0)	3; (0 to 8.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	1
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3017
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

9. Secondary Outcome

Title	Stage 2: Duration of Response (DoR)
Description	[Not Specified]
Time Frame	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months)

Outcome Measure Data

Analysis Population Description

The population for analyzing DoR is the number of participants with response of CR or PR. There was only one participant in 200 mg Abemaciclib arm and one participant in Gemcitabine/Capecitabine arm. Due to small number of participants, the data is not analyzable using the planned time to event analysis.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

10. Secondary Outcome

Title	Stage 2: Overall Survival (OS)
Description	OS duration is measured from the date of randomization to the date of death from any cause. for participants who is not known to have died as of the data-inclusion cutoff date, OS was censored at the last known alive date. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time Frame	Baseline to Death from Any Cause (Up to 10 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Abemaciclib 200mg: 11, Abemaciclib 150mg + LY3023414 150mg: 12, Gemcitabine + Capecitabine: 21;

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	33	33	33
Median (95% Confidence Interval); Unit of Measure: Months
	2.71; (1.97 to 5.36)	3.29; (1.97 to 5.03)	NA [1]; (2.53 to NA)

[1]

Data did not allow it to be estimable.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1938
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.600
	Confidence Interval	(2-Sided) 95%; 0.782 to 3.272
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2477
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.533
	Confidence Interval	(2-Sided) 95%; 0.746 to 3.150
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level
Description	No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and post baseline CA 19-9 measurement.

Arm/Group Title	200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:	Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed	24	21	20
Mean (Standard Deviation); Unit of Measure: U/mL
	4281.53 (8177.89)	3225.29 (5730.25)	-501.17 (7198.70)

12. Secondary Outcome

Title	Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)
Description	mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours, and typical completion time for this instrument is less than 5 minutes. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline & post baseline value for the mBPI-sf specified item.

Arm/Group Title		200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:		Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed		19	14	13
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
Pain at its Worst in Last 24 hours	Number Analyzed	19 participants	14 participants	13 participants
		0.63 (0.47)	-0.33 (0.55)	-0.02 (0.57)
Pain at its Least in Last 24 hours	Number Analyzed	19 participants	14 participants	13 participants
		0.86 (0.42)	0.18 (0.49)	0.39 (0.51)
Pain on the Average	Number Analyzed	18 participants	14 participants	13 participants
		0.62 (0.45)	-0.03 (0.51)	-0.07 (0.53)
Pain Right Now	Number Analyzed	19 participants	14 participants	13 participants
		0.38 (0.34)	0.34 (0.59)	-0.38 (0.61)
Pain Interfered General Activity	Number Analyzed	19 participants	14 participants	13 participants
		0.64 (0.47)	0.07 (0.55)	0.22 (0.57)
Pain Interfered with Mood	Number Analyzed	19 participants	14 participants	13 participants
		0.54 (0.41)	0.28 (0.48)	0.60 (0.50)
Pain Interfered Walking Ability	Number Analyzed	19 participants	14 participants	13 participants
		0.05 (0.55)	0.83 (0.64)	0.19 (0.67)
Pain Interfered with Normal Work	Number Analyzed	19 participants	14 participants	13 participants
		1.07 (0.51)	0.66 (0.59)	0.19 (0.61)
Pain Interfered with Relations	Number Analyzed	19 participants	14 participants	13 participants
		0.39 (0.52)	0.67 (0.61)	0.26 (0.63)
Pain Interfered with Sleep	Number Analyzed	19 participants	14 participants	13 participants
		0.19 (0.53)	0.34 (0.61)	-0.56 (0.65)
Pain Interfered Enjoyment of Life	Number Analyzed	19 participants	14 participants	13 participants
		0.69 (0.62)	0.39 (0.72)	-0.13 (0.75)
BPI Mean Pain Interference Score	Number Analyzed	19 participants	14 participants	13 participants
		0.55 (0.44)	0.50 (0.51)	0.05 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain at its Worst in Last 24 Hours
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.383
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; -0.84 to 2.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain at its Worst in Last 24 Hours
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.692
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -1.91 to 1.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain at its Least in Last 24 Hours
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.469
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; -0.85 to 1.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.66
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain at its Least in Last 24 Hours
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.776
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -1.62 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain on the Average
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.328
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; -0.72 to 2.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain on the Average
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.954
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -1.45 to 1.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Right Now
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.350
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -0.85 to 2.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.80
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain right now.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.405
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; -1.01 to 2.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered General Activity
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.565
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; -1.06 to 1.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain Interfered General Activity
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.848
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -1.74 to 1.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered with Mood
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.928
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -1.37 to 1.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.65
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain Interfered with Mood
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.650
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -1.71 to 1.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.69
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered Walking Ability
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.865
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -1.89 to 1.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.86
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain Interfered Walking Ability
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.497
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; -1.23 to 2.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.92
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered with Normal Work
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.272
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; -0.72 to 2.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.80
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain Interfered with Normal Work
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.583
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; -1.25 to 2.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered with Relations
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.876
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; -1.53 to 1.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.82
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered with relations.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.644
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; -1.37 to 2.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered with Sleep
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.384
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -0.97 to 2.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.318
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; -0.90 to 2.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.89
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Pain Interfered Enjoyment of Life
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.407
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; -1.15 to 2.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.97
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Pain Interfered Enjoyment of Life
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.620
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; -1.58 to 2.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.04
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	BPI-Mean Interference Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.475
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -0.90 to 1.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	BPI-Mean Interference Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.540
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; -1.04 to 1.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Description	The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent).; Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much); Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline & post baseline value for the EORTC QLQ-C30 specified item.

Arm/Group Title		200mg Abemaciclib	150mg Abemaciclib + 150mg LY3023414	Gemcitabine or Capecitabine
Arm/Group Description:		Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
Overall Number of Participants Analyzed		19	14	14
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
Global Health Status	Number Analyzed	19 participants	14 participants	13 participants
		-6.21 (3.87)	-4.82 (4.50)	-2.40 (4.64)
Functional Scales: Physical Functioning	Number Analyzed	19 participants	14 participants	14 participants
		-14.44 (4.40)	-11.65 (5.12)	-5.42 (5.12)
Functional Scales: Role Functioning	Number Analyzed	19 participants	14 participants	14 participants
		-17.09 (6.17)	-18.05 (7.32)	-17.10 (7.36)
Functional Scales: Emotional Functioning	Number Analyzed	19 participants	14 participants	13 participants
		-4.89 (4.49)	-0.63 (5.22)	2.06 (5.41)
Functional Scales: Cognitive Functioning	Number Analyzed	19 participants	14 participants	13 participants
		-10.43 (4.10)	-8.39 (4.77)	-5.18 (4.95)
Functional Scale: Social Functioning	Number Analyzed	19 participants	14 participants	13 participants
		-21.12 (4.90)	-17.09 (5.72)	-2.00 (5.95)
Symptom Scales: Fatigue	Number Analyzed	19 participants	14 participants	14 participants
		14.13 (4.92)	14.90 (5.73)	5.64 (5.71)
Symptom Scales: Nausea and Vomiting	Number Analyzed	19 participants	14 participants	14 participants
		7.98 (5.57)	9.42 (6.47)	11.88 (6.50)
Symptom Scales: Pain	Number Analyzed	19 participants	14 participants	14 participants
		9.79 (5.63)	2.68 (6.61)	5.43 (6.62)
Symptom Scale: Dysopnea	Number Analyzed	19 participants	14 participants	14 participants
		0.35 (5.48)	11.19 (6.38)	-4.51 (6.36)
Symptom Scale: Insomnia	Number Analyzed	19 participants	14 participants	14 participants
		-5.19 (5.17)	1.83 (6.01)	-6.71 (6.05)
Symptom Scale: Appetite Loss	Number Analyzed	19 participants	14 participants	12 participants
		12.54 (5.79)	15.32 (6.77)	9.51 (7.30)
Symptom Scale: Constipation	Number Analyzed	19 participants	14 participants	13 participants
		2.96 (5.95)	-6.51 (6.96)	12.93 (7.15)
Symptom Scale: Diarrhoea	Number Analyzed	19 participants	14 participants	13 participants
		15.71 (6.76)	26.28 (7.83)	20.51 (7.98)
Symptom Scale: Financial difficulties	Number Analyzed	19 participants	14 participants	13 participants
		3.96 (4.82)	2.45 (5.68)	-3.30 (5.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Global health status
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.818
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-1.39
	Confidence Interval	(2-Sided) 95%; -13.46 to 10.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.98
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Global health status
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.533
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.80
	Confidence Interval	(2-Sided) 95%; -16.03 to 8.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.06
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Functional Scales: Physical functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.681
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.79
	Confidence Interval	(2-Sided) 95%; -16.40 to 10.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.75
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Functional Scales: Physical functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.189
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-9.02
	Confidence Interval	(2-Sided) 95%; -22.63 to 4.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.75
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Functional Scales: Role functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.921
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; -18.29 to 20.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.54
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Functional Scales: Role functioning.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.999
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -19.40 to 19.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.62
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Functional Scales: Emotional functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.541
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-4.26
	Confidence Interval	(2-Sided) 95%; -18.20 to 9.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.91
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Functional Scales: Emotional functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.330
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-6.95
	Confidence Interval	(2-Sided) 95%; -21.17 to 7.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.05
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Functional Scales: Cognitive Functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.747
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.04
	Confidence Interval	(2-Sided) 95%; -14.74 to 10.66
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.29
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Functional Scales: Cognitive functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.419
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-5.25
	Confidence Interval	(2-Sided) 95%; -18.22 to 7.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.43
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Functional Scales: Social functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.596
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-4.02
	Confidence Interval	(2-Sided) 95%; -19.23 to 11.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.53
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Functional Scales: Social functioning
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.017
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-19.12
	Confidence Interval	(2-Sided) 95%; -34.68 to -3.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.71
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptoms Scales: Fatigue
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.919
	Comments	Social Scales: Fatigue
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -16.03 to 14.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.57
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Fatigue
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.267
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	8.48
	Confidence Interval	(2-Sided) 95%; -6.72 to 23.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.54
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Nausea and Vomiting
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.866
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-1.45
	Confidence Interval	(2-Sided) 95%; -18.66 to 15.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.54
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Nausea and Vomiting
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.652
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.90
	Confidence Interval	(2-Sided) 95%; -21.23 to 13.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.59
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Pain
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.417
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	7.11
	Confidence Interval	(2-Sided) 95%; -10.39 to 24.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.67
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Pain
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.618
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	4.36
	Confidence Interval	(2-Sided) 95%; -13.16 to 21.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.69
	Estimation Comments	[Not Specified]

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Dyspnoea
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.206
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-10.84
	Confidence Interval	(2-Sided) 95%; -27.85 to 6.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.44
	Estimation Comments	[Not Specified]

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Dyspnoea
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.566
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	4.86
	Confidence Interval	(2-Sided) 95%; -12.08 to 21.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.40
	Estimation Comments	[Not Specified]

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Insomnia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.380
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-7.02
	Confidence Interval	(2-Sided) 95%; -23.01 to 8.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.93
	Estimation Comments	[Not Specified]

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Insomnia
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.850
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	1.52
	Confidence Interval	(2-Sided) 95%; -14.60 to 17.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.99
	Estimation Comments	[Not Specified]

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Appetite loss
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.756
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.79
	Confidence Interval	(2-Sided) 95%; -20.78 to 15.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.91
	Estimation Comments	[Not Specified]

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Appetite loss
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.747
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	3.02
	Confidence Interval	(2-Sided) 95%; -15.77 to 21.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.31
	Estimation Comments	[Not Specified]

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Constipation
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.311
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	9.47
	Confidence Interval	(2-Sided) 95%; -9.16 to 28.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.23
	Estimation Comments	[Not Specified]

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Constipation
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.290
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-9.97
	Confidence Interval	(2-Sided) 95%; -28.75 to 8.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.30
	Estimation Comments	[Not Specified]

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Diarrhoea
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.323
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-10.57
	Confidence Interval	(2-Sided) 95%; -31.93 to 10.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.58
	Estimation Comments	[Not Specified]

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Diarrhoea
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.651
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-4.80
	Confidence Interval	(2-Sided) 95%; -26.08 to 16.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 10.54
	Estimation Comments	[Not Specified]

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	200mg Abemaciclib, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Financial Difficulties
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.841
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; -13.57 to 16.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.47
	Estimation Comments	[Not Specified]

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	150mg Abemaciclib + 150mg LY3023414, Gemcitabine or Capecitabine
	Comments	Symptom Scales: Financial Difficulties
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.344
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	7.26
	Confidence Interval	(2-Sided) 95%; -8.03 to 22.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.57
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414
Description	Mean steady state exposure was reported by trough pre-dose plasma concentrations.
Time Frame	C2D1: 0h, C3D1: 0h, C4D1: 0h

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of 150mg LY3023414 and had evaluable PK samples.

Arm/Group Title	150mg Abemaciclib + 150mg LY3023414
Arm/Group Description:	Participants received oral dose of 150mg Abemaciclib twice daily along with 150mg LY3023414 twice daily for 28 day cycles.
Overall Number of Participants Analyzed	9
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	27.3; (450%)

15. Secondary Outcome

Title	Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose
Description	Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose.
Time Frame	C1D1: 2h Post dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of 150mg LY3023414 and had evaluable PK samples.

Arm/Group Title	150mg Abemaciclib + 150mg LY3023414
Arm/Group Description:	Participants received oral dose of 150mg Abemaciclib twice daily along with 150mg LY3023414 twice daily for 28 day cycles.
Overall Number of Participants Analyzed	28
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	518; (67%)

Adverse Events

Time Frame	Up to 30 weeks
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Arm/Group Title	150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In)		200mg Abemaciclib		150mg Abemaciclib + 150mg LY3023414		Gemcitabine or Capecitabine
Arm/Group Description	Participants received oral dose of 150mg Abemaciclib twice daily for 28 day cycles along with oral dose of 150 mg Galunisertib twice daily for 14 days of 28 days cycle.		Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.		Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.		Participants received either 1000 milligram per square meter (mg/m^2) of Gemcitabine by intravenous infusion on days 1, 8, 15 and 22 of 28 day cycle or 1250 mg/m^2 oral dose of Capecitabine twice daily for 14 days of 21 day cycle.
All-Cause Mortality
	150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In)		200mg Abemaciclib		150mg Abemaciclib + 150mg LY3023414		Gemcitabine or Capecitabine
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	5/7 (71.43%)		22/32 (68.75%)		21/33 (63.64%)		12/26 (46.15%)
Serious Adverse Events
	150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In)		200mg Abemaciclib		150mg Abemaciclib + 150mg LY3023414		Gemcitabine or Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.14%)		17/32 (53.13%)		18/33 (54.55%)		15/26 (57.69%)
Blood and lymphatic system disorders
Anaemia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Febrile neutropenia † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	1	1/26 (3.85%)	1
Neutropenia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Thrombocytopenia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	8	0/26 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/7 (0.00%)	0	2/32 (6.25%)	2	0/33 (0.00%)	0	1/26 (3.85%)	1
Ascites † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Diarrhoea † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	1	1/26 (3.85%)	1
Duodenal stenosis † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Gastric ulcer haemorrhage † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Gastrointestinal perforation † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Intestinal obstruction † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Large intestinal obstruction † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Nausea † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	1/26 (3.85%)	1
Obstruction gastric † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Oesophagitis † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Stomatitis † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	2	1/26 (3.85%)	1
Subileus † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Vomiting † 1	0/7 (0.00%)	0	1/32 (3.13%)	2	2/33 (6.06%)	2	4/26 (15.38%)	4
General disorders
Asthenia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Chills † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Fatigue † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	1/33 (3.03%)	1	0/26 (0.00%)	0
General physical health deterioration † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Malaise † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Multiple organ dysfunction syndrome † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Pyrexia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	3	0/26 (0.00%)	0
Systemic inflammatory response syndrome † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Hepatobiliary disorders
Bile duct obstruction † 1	0/7 (0.00%)	0	2/32 (6.25%)	2	0/33 (0.00%)	0	1/26 (3.85%)	1
Cholangitis † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	2	1/26 (3.85%)	1
Cholangitis acute † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	2
Infections and infestations
Abdominal infection † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	2	0/26 (0.00%)	0
Bacteraemia † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	1	1/26 (3.85%)	1
Escherichia bacteraemia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Peritonitis bacterial † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Sepsis † 1	1/7 (14.29%)	1	1/32 (3.13%)	2	1/33 (3.03%)	1	0/26 (0.00%)	0
Upper respiratory tract infection † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Urosepsis † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Investigations
Blood creatinine increased † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	1	0/26 (0.00%)	0
Platelet count decreased † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
White blood cell count decreased † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Metabolism and nutrition disorders
Acidosis † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Decreased appetite † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Dehydration † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Failure to thrive † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Hypokalaemia † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Hyponatraemia † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	1	1/26 (3.85%)	1
Hypophosphataemia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	1/26 (3.85%)	1
Tumour lysis syndrome † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Muscular weakness † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Nervous system disorders
Cerebrovascular accident † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	1/33 (3.03%)	2	0/26 (0.00%)	0
Ischaemic cerebral infarction † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Psychiatric disorders
Confusional state † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Mental status changes † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Pleural effusion † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Pulmonary embolism † 1	1/7 (14.29%)	1	2/32 (6.25%)	2	1/33 (3.03%)	1	1/26 (3.85%)	1
Respiratory failure † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Vascular disorders
Deep vein thrombosis † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Embolism † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Hypotension † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In)		200mg Abemaciclib		150mg Abemaciclib + 150mg LY3023414		Gemcitabine or Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100.00%)		30/32 (93.75%)		33/33 (100.00%)		25/26 (96.15%)
Blood and lymphatic system disorders
Anaemia † 1	3/7 (42.86%)	14	10/32 (31.25%)	18	6/33 (18.18%)	7	11/26 (42.31%)	19
Cytopenia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Leukopenia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Neutropenia † 1	2/7 (28.57%)	2	4/32 (12.50%)	9	0/33 (0.00%)	0	2/26 (7.69%)	5
Thrombocytopenia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	5/33 (15.15%)	5	4/26 (15.38%)	17
Cardiac disorders
Tachycardia † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	1/33 (3.03%)	1	0/26 (0.00%)	0
Endocrine disorders
Hypothyroidism † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Eye disorders
Photopsia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Visual impairment † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	2/7 (28.57%)	2	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Abdominal distension † 1	1/7 (14.29%)	2	1/32 (3.13%)	1	0/33 (0.00%)	0	1/26 (3.85%)	1
Abdominal pain † 1	1/7 (14.29%)	1	7/32 (21.88%)	8	5/33 (15.15%)	5	6/26 (23.08%)	8
Abdominal pain upper † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	1/33 (3.03%)	1	4/26 (15.38%)	4
Ascites † 1	0/7 (0.00%)	0	4/32 (12.50%)	5	2/33 (6.06%)	2	3/26 (11.54%)	3
Constipation † 1	1/7 (14.29%)	2	5/32 (15.63%)	6	2/33 (6.06%)	2	7/26 (26.92%)	7
Diarrhoea † 1	4/7 (57.14%)	4	12/32 (37.50%)	21	17/33 (51.52%)	19	8/26 (30.77%)	16
Dry mouth † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	2	0/26 (0.00%)	0
Dyspepsia † 1	0/7 (0.00%)	0	2/32 (6.25%)	2	0/33 (0.00%)	0	0/26 (0.00%)	0
Eructation † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Flatulence † 1	0/7 (0.00%)	0	2/32 (6.25%)	2	1/33 (3.03%)	1	0/26 (0.00%)	0
Gastrointestinal pain † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Nausea † 1	5/7 (71.43%)	5	9/32 (28.13%)	14	15/33 (45.45%)	18	9/26 (34.62%)	10
Stomatitis † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	12/33 (36.36%)	16	6/26 (23.08%)	9
Vomiting † 1	2/7 (28.57%)	3	10/32 (31.25%)	12	15/33 (45.45%)	22	6/26 (23.08%)	8
General disorders
Asthenia † 1	1/7 (14.29%)	1	4/32 (12.50%)	5	0/33 (0.00%)	0	0/26 (0.00%)	0
Chills † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	2/33 (6.06%)	2	0/26 (0.00%)	0
Fatigue † 1	4/7 (57.14%)	7	16/32 (50.00%)	22	17/33 (51.52%)	25	11/26 (42.31%)	12
Feeling cold † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
General physical health deterioration † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	2/33 (6.06%)	3	3/26 (11.54%)	3
Malaise † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	0/33 (0.00%)	0	0/26 (0.00%)	0
Non-cardiac chest pain † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	2/26 (7.69%)	2
Oedema † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Oedema peripheral † 1	2/7 (28.57%)	2	4/32 (12.50%)	4	5/33 (15.15%)	6	1/26 (3.85%)	1
Peripheral swelling † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Pyrexia † 1	2/7 (28.57%)	2	3/32 (9.38%)	5	5/33 (15.15%)	6	0/26 (0.00%)	0
Hepatobiliary disorders
Bile duct obstruction † 1	0/7 (0.00%)	0	4/32 (12.50%)	4	0/33 (0.00%)	0	0/26 (0.00%)	0
Infections and infestations
Bacterial sepsis † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Upper respiratory tract infection † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	2/26 (7.69%)	2
Urinary tract infection † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	0/33 (0.00%)	0	1/26 (3.85%)	1
Injury, poisoning and procedural complications
Fall † 1	0/7 (0.00%)	0	1/32 (3.13%)	1	2/33 (6.06%)	2	0/26 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/7 (14.29%)	1	4/32 (12.50%)	8	0/33 (0.00%)	0	1/26 (3.85%)	1
Aspartate aminotransferase increased † 1	2/7 (28.57%)	3	3/32 (9.38%)	6	0/33 (0.00%)	0	1/26 (3.85%)	3
Blood alkaline phosphatase increased † 1	1/7 (14.29%)	1	5/32 (15.63%)	9	3/33 (9.09%)	5	1/26 (3.85%)	1
Blood bilirubin increased † 1	0/7 (0.00%)	0	5/32 (15.63%)	16	1/33 (3.03%)	1	1/26 (3.85%)	2
Blood creatinine increased † 1	1/7 (14.29%)	1	1/32 (3.13%)	2	3/33 (9.09%)	5	1/26 (3.85%)	3
Blood potassium decreased † 1	0/7 (0.00%)	0	2/32 (6.25%)	2	0/33 (0.00%)	0	0/26 (0.00%)	0
Blood sodium decreased † 1	0/7 (0.00%)	0	2/32 (6.25%)	3	0/33 (0.00%)	0	0/26 (0.00%)	0
International normalised ratio increased † 1	0/7 (0.00%)	0	2/32 (6.25%)	2	0/33 (0.00%)	0	0/26 (0.00%)	0
Lymphocyte count decreased † 1	0/7 (0.00%)	0	2/32 (6.25%)	3	0/33 (0.00%)	0	2/26 (7.69%)	4
Neutrophil count decreased † 1	0/7 (0.00%)	0	4/32 (12.50%)	7	1/33 (3.03%)	3	2/26 (7.69%)	8
Occult blood positive † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Platelet count decreased † 1	0/7 (0.00%)	0	10/32 (31.25%)	20	5/33 (15.15%)	11	4/26 (15.38%)	9
Weight decreased † 1	2/7 (28.57%)	2	0/32 (0.00%)	0	3/33 (9.09%)	3	1/26 (3.85%)	1
White blood cell count decreased † 1	2/7 (28.57%)	3	4/32 (12.50%)	4	1/33 (3.03%)	3	3/26 (11.54%)	5
Metabolism and nutrition disorders
Decreased appetite † 1	3/7 (42.86%)	4	9/32 (28.13%)	11	8/33 (24.24%)	9	8/26 (30.77%)	8
Dehydration † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	2/33 (6.06%)	2	1/26 (3.85%)	1
Failure to thrive † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Fluid retention † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Hyperglycaemia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	3/33 (9.09%)	5	1/26 (3.85%)	1
Hyperkalaemia † 1	0/7 (0.00%)	0	1/32 (3.13%)	2	2/33 (6.06%)	2	2/26 (7.69%)	2
Hypoalbuminaemia † 1	2/7 (28.57%)	5	1/32 (3.13%)	1	3/33 (9.09%)	3	1/26 (3.85%)	1
Hypocalcaemia † 1	1/7 (14.29%)	2	1/32 (3.13%)	4	0/33 (0.00%)	0	0/26 (0.00%)	0
Hypokalaemia † 1	0/7 (0.00%)	0	3/32 (9.38%)	4	3/33 (9.09%)	3	4/26 (15.38%)	5
Hypomagnesaemia † 1	1/7 (14.29%)	1	3/32 (9.38%)	3	1/33 (3.03%)	1	1/26 (3.85%)	1
Hyponatraemia † 1	4/7 (57.14%)	6	1/32 (3.13%)	1	3/33 (9.09%)	6	1/26 (3.85%)	1
Hypophagia † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Hypophosphataemia † 1	0/7 (0.00%)	0	2/32 (6.25%)	3	1/33 (3.03%)	2	1/26 (3.85%)	1
Musculoskeletal and connective tissue disorders
Arthropathy † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Back pain † 1	1/7 (14.29%)	1	3/32 (9.38%)	3	0/33 (0.00%)	0	0/26 (0.00%)	0
Flank pain † 1	1/7 (14.29%)	2	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Muscular weakness † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	3	0/26 (0.00%)	0
Musculoskeletal pain † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Myalgia † 1	0/7 (0.00%)	0	2/32 (6.25%)	3	1/33 (3.03%)	2	0/26 (0.00%)	0
Pain in extremity † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	1/33 (3.03%)	1	1/26 (3.85%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	0/7 (0.00%)	0	2/32 (6.25%)	3	0/33 (0.00%)	0	0/26 (0.00%)	0
Nervous system disorders
Dizziness † 1	2/7 (28.57%)	2	1/32 (3.13%)	1	3/33 (9.09%)	3	0/26 (0.00%)	0
Dysgeusia † 1	0/7 (0.00%)	0	3/32 (9.38%)	3	4/33 (12.12%)	4	0/26 (0.00%)	0
Psychiatric disorders
Anxiety † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	0/33 (0.00%)	0	1/26 (3.85%)	1
Confusional state † 1	0/7 (0.00%)	0	3/32 (9.38%)	3	0/33 (0.00%)	0	1/26 (3.85%)	1
Depression † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	1/33 (3.03%)	1	0/26 (0.00%)	0
Insomnia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	3	0/26 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/7 (0.00%)	0	1/32 (3.13%)	2	0/33 (0.00%)	0	3/26 (11.54%)	3
Haematuria † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Hydronephrosis † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Reproductive system and breast disorders
Prostatomegaly † 1	0/3 (0.00%)	0	0/14 (0.00%)	0	1/17 (5.88%)	1	0/10 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Cough † 1	1/7 (14.29%)	1	2/32 (6.25%)	2	2/33 (6.06%)	2	2/26 (7.69%)	2
Dysphonia † 1	1/7 (14.29%)	2	0/32 (0.00%)	0	0/33 (0.00%)	0	1/26 (3.85%)	1
Dyspnoea † 1	2/7 (28.57%)	2	2/32 (6.25%)	2	4/33 (12.12%)	5	3/26 (11.54%)	5
Hypoxia † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	2	0/26 (0.00%)	0
Pleural effusion † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	2/33 (6.06%)	2	1/26 (3.85%)	1
Pneumothorax † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	2/26 (7.69%)	4
Upper-airway cough syndrome † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Skin and subcutaneous tissue disorders
Dry skin † 1	1/7 (14.29%)	1	1/32 (3.13%)	1	1/33 (3.03%)	1	1/26 (3.85%)	1
Ecchymosis † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Palmar-plantar erythrodysaesthesia syndrome † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	2/33 (6.06%)	2	10/26 (38.46%)	24
Pruritus † 1	2/7 (28.57%)	2	2/32 (6.25%)	2	2/33 (6.06%)	2	1/26 (3.85%)	1
Rash † 1	2/7 (28.57%)	3	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Rash maculo-papular † 1	0/7 (0.00%)	0	1/32 (3.13%)	3	3/33 (9.09%)	3	1/26 (3.85%)	1
Skin discolouration † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
Skin ulcer † 1	0/7 (0.00%)	0	0/32 (0.00%)	0	0/33 (0.00%)	0	2/26 (7.69%)	2
Vascular disorders
Hot flush † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	1/33 (3.03%)	1	0/26 (0.00%)	0
Hypotension † 1	1/7 (14.29%)	1	3/32 (9.38%)	3	1/33 (3.03%)	1	0/26 (0.00%)	0
Peripheral coldness † 1	1/7 (14.29%)	1	0/32 (0.00%)	0	0/33 (0.00%)	0	0/26 (0.00%)	0
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

Study was planned for stage 1 & stage 2. Stage 2 did not occur, no participants were enrolled to stage 2;

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979
• EMail: ClinicalTrials.gov@lilly.com

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02981342
• Other Study ID Numbers: 16342; I3Y-MC-JPCJ ( Other Identifier: Eli Lilly and Company ); 2016-002218-36 ( EudraCT Number )
• First Submitted: December 1, 2016
• First Posted: December 5, 2016
• Results First Submitted: April 18, 2019
• Results First Posted: June 25, 2019
• Last Update Posted: November 20, 2019