Trial Outcomes & Findings for A Study of Abemaciclib (LY2835219) Alone or in Combination With Other Agents in Participants With Previously Treated Pancreatic Ductal Adenocarcinoma (NCT NCT02981342)

Last Updated: 2019-11-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

106 participants

Primary outcome timeframe

Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)

Results posted on

2019-11-20

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in) 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.	200mg Abemaciclib Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine 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 Study STARTED	7	33	33	33
Overall Study Received at Least One Dose of Study Drug	7	32	33	26
Overall Study COMPLETED	7	22	20	19
Overall Study NOT COMPLETED	0	11	13	14

Reasons for withdrawal

Reasons for withdrawal
Measure	200mg Abemaciclib Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine 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 Study Adverse Event	0	0	1
Overall Study Death	9	9	4
Overall Study Withdrawal by Subject	0	3	1
Overall Study Study closed by sponsor	0	1	1
Overall Study Randomized, Never Treated	1	0	7
Overall Study Lost to Follow-up	1	0	0

Baseline Characteristics

All randomized participants who received at least one dose of study drug.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	150mg Abemaciclib + 150mg Galunisertib (Safety Lead-in) n=7 Participants 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.	200mg Abemaciclib n=33 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=33 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=33 Participants 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 n=106 Participants Total of all reporting groups
Age, Continuous	65.29 years STANDARD_DEVIATION 6.99 • n=7 Participants • All randomized participants who received at least one dose of study drug.	61.09 years STANDARD_DEVIATION 7.83 • n=32 Participants • All randomized participants who received at least one dose of study drug.	62.52 years STANDARD_DEVIATION 8.97 • n=33 Participants • All randomized participants who received at least one dose of study drug.	66.85 years STANDARD_DEVIATION 7.61 • n=26 Participants • All randomized participants who received at least one dose of study drug.	63.40 years STANDARD_DEVIATION 8.34 • n=98 Participants • All randomized participants who received at least one dose of study drug.
Sex: Female, Male Female	4 Participants n=7 Participants	18 Participants n=33 Participants	16 Participants n=33 Participants	19 Participants n=33 Participants	57 Participants n=106 Participants
Sex: Female, Male Male	3 Participants n=7 Participants	15 Participants n=33 Participants	17 Participants n=33 Participants	14 Participants n=33 Participants	49 Participants n=106 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=7 Participants	2 Participants n=33 Participants	4 Participants n=33 Participants	3 Participants n=33 Participants	9 Participants n=106 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=7 Participants	30 Participants n=33 Participants	28 Participants n=33 Participants	24 Participants n=33 Participants	89 Participants n=106 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	6 Participants n=33 Participants	8 Participants n=106 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=106 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	7 Participants n=33 Participants	5 Participants n=33 Participants	4 Participants n=33 Participants	16 Participants n=106 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=106 Participants
Race (NIH/OMB) Black or African American	0 Participants n=7 Participants	0 Participants n=33 Participants	1 Participants n=33 Participants	3 Participants n=33 Participants	4 Participants n=106 Participants
Race (NIH/OMB) White	7 Participants n=7 Participants	26 Participants n=33 Participants	26 Participants n=33 Participants	25 Participants n=33 Participants	84 Participants n=106 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=106 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=33 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	2 Participants n=106 Participants
Region of Enrollment Belgium	0 Participants n=7 Participants	8 Participants n=33 Participants	6 Participants n=33 Participants	5 Participants n=33 Participants	19 Participants n=106 Participants
Region of Enrollment United States	7 Participants n=7 Participants	8 Participants n=33 Participants	10 Participants n=33 Participants	8 Participants n=33 Participants	33 Participants n=106 Participants
Region of Enrollment Taiwan	0 Participants n=7 Participants	7 Participants n=33 Participants	4 Participants n=33 Participants	3 Participants n=33 Participants	14 Participants n=106 Participants
Region of Enrollment United Kingdom	0 Participants n=7 Participants	1 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=33 Participants	1 Participants n=106 Participants
Region of Enrollment Israel	0 Participants n=7 Participants	2 Participants n=33 Participants	4 Participants n=33 Participants	5 Participants n=33 Participants	11 Participants n=106 Participants
Region of Enrollment Australia	0 Participants n=7 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	3 Participants n=33 Participants	5 Participants n=106 Participants
Region of Enrollment France	0 Participants n=7 Participants	1 Participants n=33 Participants	1 Participants n=33 Participants	6 Participants n=33 Participants	8 Participants n=106 Participants
Region of Enrollment Spain	0 Participants n=7 Participants	5 Participants n=33 Participants	7 Participants n=33 Participants	3 Participants n=33 Participants	15 Participants n=106 Participants

PRIMARY outcome

Timeframe: Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)

Population: All randomized participants.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=33 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=33 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=33 Participants 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.
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)	15.2 percentage of Participants Interval 2.9 to 27.4	12.1 percentage of Participants Interval 1.0 to 23.3	36.4 percentage of Participants Interval 20.0 to 52.8

PRIMARY outcome

Timeframe: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=33 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=33 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=33 Participants 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.
Stage 2: Progression Free Survival (PFS)	1.68 Months Interval 1.35 to 1.84	1.81 Months Interval 1.28 to 1.91	3.25 Months Interval 1.05 to 5.65

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)

Population: All randomized participants.

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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=33 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=33 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=33 Participants 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.
Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR	3 percentage of Participants Interval 0.0 to 8.9	0 percentage of Participants Data did not allow it to be estimable.	3 percentage of Participants Interval 0.0 to 8.9

SECONDARY outcome

Timeframe: Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose

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

Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax).

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=4 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine 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.
Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) Abemaciclib	356 Nanogram per Millilitre (ng/mL) Geometric Coefficient of Variation 137	—	—
Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) LSN2839567 (M2)	85.1 Nanogram per Millilitre (ng/mL) Geometric Coefficient of Variation 66	—	—
Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) LSN3106726 (M20)	153 Nanogram per Millilitre (ng/mL) Geometric Coefficient of Variation 58	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)

Population: All randomized participants.

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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=33 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=33 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=33 Participants 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.
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	3 percentage of participants Interval 0.0 to 8.9	0 percentage of participants Interval 0.0 to 0.0	3 percentage of participants Interval 0.0 to 8.9

SECONDARY outcome

Timeframe: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months)

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Death from Any Cause (Up to 10 Months)

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

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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=33 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=33 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=33 Participants 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.
Stage 2: Overall Survival (OS)	2.71 Months Interval 1.97 to 5.36	3.29 Months Interval 1.97 to 5.03	NA Months Interval 2.53 to Data did not allow it to be estimable.

SECONDARY outcome

Timeframe: Baseline, 6 Months

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

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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=24 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=21 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=20 Participants 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.
Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level	4281.53 U/mL Standard Deviation 8177.89	3225.29 U/mL Standard Deviation 5730.25	-501.17 U/mL Standard Deviation 7198.70

SECONDARY outcome

Timeframe: Baseline, 6 Months

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

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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=19 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=14 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=13 Participants 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.
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain at its Worst in Last 24 hours	0.63 score on a scale Standard Error 0.47	-0.33 score on a scale Standard Error 0.55	-0.02 score on a scale Standard Error 0.57
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain at its Least in Last 24 hours	0.86 score on a scale Standard Error 0.42	0.18 score on a scale Standard Error 0.49	0.39 score on a scale Standard Error 0.51
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain on the Average	0.62 score on a scale Standard Error 0.45	-0.03 score on a scale Standard Error 0.51	-0.07 score on a scale Standard Error 0.53
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Right Now	0.38 score on a scale Standard Error 0.34	0.34 score on a scale Standard Error 0.59	-0.38 score on a scale Standard Error 0.61
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered General Activity	0.64 score on a scale Standard Error 0.47	0.07 score on a scale Standard Error 0.55	0.22 score on a scale Standard Error 0.57
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered with Mood	0.54 score on a scale Standard Error 0.41	0.28 score on a scale Standard Error 0.48	0.60 score on a scale Standard Error 0.50
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered Walking Ability	0.05 score on a scale Standard Error 0.55	0.83 score on a scale Standard Error 0.64	0.19 score on a scale Standard Error 0.67
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered with Normal Work	1.07 score on a scale Standard Error 0.51	0.66 score on a scale Standard Error 0.59	0.19 score on a scale Standard Error 0.61
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered with Relations	0.39 score on a scale Standard Error 0.52	0.67 score on a scale Standard Error 0.61	0.26 score on a scale Standard Error 0.63
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered with Sleep	0.19 score on a scale Standard Error 0.53	0.34 score on a scale Standard Error 0.61	-0.56 score on a scale Standard Error 0.65
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Pain Interfered Enjoyment of Life	0.69 score on a scale Standard Error 0.62	0.39 score on a scale Standard Error 0.72	-0.13 score on a scale Standard Error 0.75
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) BPI Mean Pain Interference Score	0.55 score on a scale Standard Error 0.44	0.50 score on a scale Standard Error 0.51	0.05 score on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline, 6 Months

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

The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: 1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). 2. 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) 3. 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.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=19 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 n=14 Participants Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine n=14 Participants 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.
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) Global Health Status	-6.21 units on a scale Standard Error 3.87	-4.82 units on a scale Standard Error 4.50	-2.40 units on a scale Standard Error 4.64
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) Functional Scales: Physical Functioning	-14.44 units on a scale Standard Error 4.40	-11.65 units on a scale Standard Error 5.12	-5.42 units on a scale Standard Error 5.12
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) Functional Scales: Role Functioning	-17.09 units on a scale Standard Error 6.17	-18.05 units on a scale Standard Error 7.32	-17.10 units on a scale Standard Error 7.36
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) Functional Scales: Emotional Functioning	-4.89 units on a scale Standard Error 4.49	-0.63 units on a scale Standard Error 5.22	2.06 units on a scale Standard Error 5.41
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) Functional Scales: Cognitive Functioning	-10.43 units on a scale Standard Error 4.10	-8.39 units on a scale Standard Error 4.77	-5.18 units on a scale Standard Error 4.95
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) Functional Scale: Social Functioning	-21.12 units on a scale Standard Error 4.90	-17.09 units on a scale Standard Error 5.72	-2.00 units on a scale Standard Error 5.95
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) Symptom Scales: Fatigue	14.13 units on a scale Standard Error 4.92	14.90 units on a scale Standard Error 5.73	5.64 units on a scale Standard Error 5.71
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) Symptom Scales: Nausea and Vomiting	7.98 units on a scale Standard Error 5.57	9.42 units on a scale Standard Error 6.47	11.88 units on a scale Standard Error 6.50
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) Symptom Scales: Pain	9.79 units on a scale Standard Error 5.63	2.68 units on a scale Standard Error 6.61	5.43 units on a scale Standard Error 6.62
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) Symptom Scale: Dysopnea	0.35 units on a scale Standard Error 5.48	11.19 units on a scale Standard Error 6.38	-4.51 units on a scale Standard Error 6.36
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) Symptom Scale: Insomnia	-5.19 units on a scale Standard Error 5.17	1.83 units on a scale Standard Error 6.01	-6.71 units on a scale Standard Error 6.05
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) Symptom Scale: Appetite Loss	12.54 units on a scale Standard Error 5.79	15.32 units on a scale Standard Error 6.77	9.51 units on a scale Standard Error 7.30
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) Symptom Scale: Constipation	2.96 units on a scale Standard Error 5.95	-6.51 units on a scale Standard Error 6.96	12.93 units on a scale Standard Error 7.15
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) Symptom Scale: Diarrhoea	15.71 units on a scale Standard Error 6.76	26.28 units on a scale Standard Error 7.83	20.51 units on a scale Standard Error 7.98
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) Symptom Scale: Financial difficulties	3.96 units on a scale Standard Error 4.82	2.45 units on a scale Standard Error 5.68	-3.30 units on a scale Standard Error 5.87

SECONDARY outcome

Timeframe: C2D1: 0h, C3D1: 0h, C4D1: 0h

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

Mean steady state exposure was reported by trough pre-dose plasma concentrations.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=9 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine 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.
Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414	27.3 ng/mL Geometric Coefficient of Variation 450	—	—

SECONDARY outcome

Timeframe: C1D1: 2h Post dose

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

Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose.

Outcome measures

Outcome measures
Measure	200mg Abemaciclib n=28 Participants Participants received oral dose of 200mg Abemaciclib twice daily (BID) for 28 day cycles.	150mg Abemaciclib + 150mg LY3023414 Participants received oral dose of 150mg Abemaciclib along with 150mg LY3023414 twice daily for 28 day cycles.	Gemcitabine or Capecitabine 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.
Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose	518 ng/mL Geometric Coefficient of Variation 67	—	—

Adverse Events

150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In)

Serious events: 4 serious events

Other events: 7 other events

Deaths: 5 deaths

200mg Abemaciclib

Serious events: 17 serious events

Other events: 30 other events

Deaths: 22 deaths

150mg Abemaciclib + 150mg LY3023414

Serious events: 18 serious events

Other events: 33 other events

Deaths: 21 deaths

Gemcitabine or Capecitabine

Serious events: 15 serious events

Other events: 25 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place