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

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The purpose of this study is to evaluate the safety and efficacy of abemaciclib alone and in combination with other drugs versus standard of care in participants with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).

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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) [Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)]. Number, percentage of Participants (95% Confidence Interval). 200mg Abemaciclib (n=33): 15.2 (2.9 to 27.4); 150mg Abemaciclib + 150mg LY3023414 (n=33): 12.1 (1.0 to 23.3); Gemcitabine or Capecitabine (n=33): 36.4 (20 to 52.8). Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: p=0.0495; Cochran-Mantel-Haenszel; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: p=0.0230; Cochran-Mantel-Haenszel; superiority.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Stage 2: Progression Free Survival (PFS) [Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)]. Median, Months (95% Confidence Interval). 200mg Abemaciclib (n=33): 1.68 (1.35 to 1.84); 150mg Abemaciclib + 150mg LY3023414 (n=33): 1.81 (1.28 to 1.91); Gemcitabine or Capecitabine (n=33): 3.25 (1.05 to 5.65). Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: p=0.0085; Log Rank; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: p=0.0123; Log Rank; superiority.

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Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR [Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)]. Number, percentage of Participants (95% Confidence Interval). 200mg Abemaciclib (n=33): 3 (0 to 8.9); 150mg Abemaciclib + 150mg LY3023414 (n=33): 0 (NA to NA) [Data did not allow it to be estimable.]; Gemcitabine or Capecitabine (n=33): 3 (0 to 8.9). Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: p=1; Cochran-Mantel-Haenszel; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: p=0.3017; Cochran-Mantel-Haenszel; superiority.

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Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) [Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose]. Geometric Mean, Nanogram per Millilitre (ng/mL) (Geometric Coefficient of Variation). Abemaciclib: 150mg Abemaciclib + 150mg Galunisertib (n=4): 356 (137). LSN2839567 (M2): 150mg Abemaciclib + 150mg Galunisertib (n=4): 85.1 (66). LSN3106726 (M20): 150mg Abemaciclib + 150mg Galunisertib (n=4): 153 (58).

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Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414 [Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)].

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Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414 [Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD [Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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 [Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)]. Number, percentage of participants (95% Confidence Interval). 200mg Abemaciclib (n=33): 3 (0 to 8.9); 150mg Abemaciclib + 150mg LY3023414 (n=33): 0 (0 to 0); Gemcitabine or Capecitabine (n=33): 3 (0 to 8.9). Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: p=1; Cochran-Mantel-Haenszel; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: p=0.3017; Cochran-Mantel-Haenszel; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 2: Duration of Response (DoR) [Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months)].

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Stage 2: Overall Survival (OS) [Baseline to Death from Any Cause (Up to 10 Months)]. Median, Months (95% Confidence Interval). 200mg Abemaciclib (n=33): 2.71 (1.97 to 5.36); 150mg Abemaciclib + 150mg LY3023414 (n=33): 3.29 (1.97 to 5.03); Gemcitabine or Capecitabine (n=33): NA (2.53 to NA) [Data did not allow it to be estimable.]. Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: Hazard Ratio (HR) 1.600 (95% CI 0.782 to 3.272); p=0.1938; Log Rank; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: Hazard Ratio (HR) 1.533 (95% CI 0.746 to 3.150); p=0.2477; Log Rank; superiority.

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Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level [Baseline, 6 Months]. Mean, U/mL (Standard Deviation). 200mg Abemaciclib (n=24): 4281.53 (8177.89); 150mg Abemaciclib + 150mg LY3023414 (n=21): 3225.29 (5730.25); Gemcitabine or Capecitabine (n=20): -501.17 (7198.70).

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Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) [Baseline, 6 Months]. Least Squares Mean, score on a scale (Standard Error). Pain at its Worst in Last 24 hours: 200mg Abemaciclib (n=19): 0.63 (0.47); 150mg Abemaciclib + 150mg LY3023414 (n=14): -0.33 (0.55); Gemcitabine or Capecitabine (n=13): -0.02 (0.57). Pain at its Least in Last 24 hours: 200mg Abemaciclib (n=19): 0.86 (0.42); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.18 (0.49); Gemcitabine or Capecitabine (n=13): 0.39 (0.51). Pain on the Average: 200mg Abemaciclib (n=19): 0.62 (0.45); 150mg Abemaciclib + 150mg LY3023414 (n=14): -0.03 (0.51); Gemcitabine or Capecitabine (n=13): -0.07 (0.53). Pain Right Now: 200mg Abemaciclib (n=19): 0.38 (0.34); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.34 (0.59); Gemcitabine or Capecitabine (n=13): -0.38 (0.61). Pain Interfered General Activity: 200mg Abemaciclib (n=19): 0.64 (0.47); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.07 (0.55); Gemcitabine or Capecitabine (n=13): 0.22 (0.57). Pain Interfered with Mood: 200mg Abemaciclib (n=19): 0.54 (0.41); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.28 (0.48); Gemcitabine or Capecitabine (n=13): 0.60 (0.50). Pain Interfered Walking Ability: 200mg Abemaciclib (n=19): 0.05 (0.55); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.83 (0.64); Gemcitabine or Capecitabine (n=13): 0.19 (0.67). Pain Interfered with Normal Work: 200mg Abemaciclib (n=19): 1.07 (0.51); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.66 (0.59); Gemcitabine or Capecitabine (n=13): 0.19 (0.61). Pain Interfered with Relations: 200mg Abemaciclib (n=19): 0.39 (0.52); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.67 (0.61); Gemcitabine or Capecitabine (n=13): 0.26 (0.63). Pain Interfered with Sleep: 200mg Abemaciclib (n=19): 0.19 (0.53); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.34 (0.61); Gemcitabine or Capecitabine (n=13): -0.56 (0.65). Pain Interfered Enjoyment of Life: 200mg Abemaciclib (n=19): 0.69 (0.62); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.39 (0.72); Gemcitabine or Capecitabine (n=13): -0.13 (0.75). BPI Mean Pain Interference Score: 200mg Abemaciclib (n=19): 0.55 (0.44); 150mg Abemaciclib + 150mg LY3023414 (n=14): 0.50 (0.51); Gemcitabine or Capecitabine (n=13): 0.05 (0.54). Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: LSMean Difference 0.65 (95% CI -0.84 to 2.13); p=0.383; Mixed Models Analysis; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: LSMean Difference -0.31 (95% CI -1.91 to 1.28); p=0.692; Mixed Models Analysis; superiority. Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: LSMean Difference 0.48 (95% CI -0.85 to 1.80); p=0.469; Mixed Models Analysis; superiority. Analysis, 150mg Abemaciclib + 150mg LY3023414 vs Gemcitabine or Capecitabine: LSMean Difference -0.20 (95% CI -1.62 to 1.22); p=0.776; Mixed Models Analysis; superiority. Analysis, 200mg Abemaciclib vs Gemcita

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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) [Baseline, 6 Months]. Least Squares Mean, units on a scale (Standard Error). Global Health Status: 200mg Abemaciclib (n=19): -6.21 (3.87); 150mg Abemaciclib + 150mg LY3023414 (n=14): -4.82 (4.50); Gemcitabine or Capecitabine (n=14): -2.40 (4.64). Functional Scales: Physical Functioning: 200mg Abemaciclib (n=19): -14.44 (4.40); 150mg Abemaciclib + 150mg LY3023414 (n=14): -11.65 (5.12); Gemcitabine or Capecitabine (n=14): -5.42 (5.12). Functional Scales: Role Functioning: 200mg Abemaciclib (n=19): -17.09 (6.17); 150mg Abemaciclib + 150mg LY3023414 (n=14): -18.05 (7.32); Gemcitabine or Capecitabine (n=14): -17.10 (7.36). Functional Scales: Emotional Functioning: 200mg Abemaciclib (n=19): -4.89 (4.49); 150mg Abemaciclib + 150mg LY3023414 (n=14): -0.63 (5.22); Gemcitabine or Capecitabine (n=14): 2.06 (5.41). Functional Scales: Cognitive Functioning: 200mg Abemaciclib (n=19): -10.43 (4.10); 150mg Abemaciclib + 150mg LY3023414 (n=14): -8.39 (4.77); Gemcitabine or Capecitabine (n=14): -5.18 (4.95). Functional Scale: Social Functioning: 200mg Abemaciclib (n=19): -21.12 (4.90); 150mg Abemaciclib + 150mg LY3023414 (n=14): -17.09 (5.72); Gemcitabine or Capecitabine (n=14): -2.00 (5.95). Symptom Scales: Fatigue: 200mg Abemaciclib (n=19): 14.13 (4.92); 150mg Abemaciclib + 150mg LY3023414 (n=14): 14.90 (5.73); Gemcitabine or Capecitabine (n=14): 5.64 (5.71). Symptom Scales: Nausea and Vomiting: 200mg Abemaciclib (n=19): 7.98 (5.57); 150mg Abemaciclib + 150mg LY3023414 (n=14): 9.42 (6.47); Gemcitabine or Capecitabine (n=14): 11.88 (6.50). Symptom Scales: Pain: 200mg Abemaciclib (n=19): 9.79 (5.63); 150mg Abemaciclib + 150mg LY3023414 (n=14): 2.68 (6.61); Gemcitabine or Capecitabine (n=14): 5.43 (6.62). Symptom Scale: Dysopnea: 200mg Abemaciclib (n=19): 0.35 (5.48); 150mg Abemaciclib + 150mg LY3023414 (n=14): 11.19 (6.38); Gemcitabine or Capecitabine (n=14): -4.51 (6.36). Symptom Scale: Insomnia: 200mg Abemaciclib (n=19): -5.19 (5.17); 150mg Abemaciclib + 150mg LY3023414 (n=14): 1.83 (6.01); Gemcitabine or Capecitabine (n=14): -6.71 (6.05). Symptom Scale: Appetite Loss: 200mg Abemaciclib (n=19): 12.54 (5.79); 150mg Abemaciclib + 150mg LY3023414 (n=14): 15.32 (6.77); Gemcitabine or Capecitabine (n=14): 9.51 (7.30). Symptom Scale: Constipation: 200mg Abemaciclib (n=19): 2.96 (5.95); 150mg Abemaciclib + 150mg LY3023414 (n=14): -6.51 (6.96); Gemcitabine or Capecitabine (n=14): 12.93 (7.15). Symptom Scale: Diarrhoea: 200mg Abemaciclib (n=19): 15.71 (6.76); 150mg Abemaciclib + 150mg LY3023414 (n=14): 26.28 (7.83); Gemcitabine or Capecitabine (n=14): 20.51 (7.98). Symptom Scale: Financial difficulties: 200mg Abemaciclib (n=19): 3.96 (4.82); 150mg Abemaciclib + 150mg LY3023414 (n=14): 2.45 (5.68); Gemcitabine or Capecitabine (n=14): -3.30 (5.87). Analysis, 200mg Abemaciclib vs Gemcitabine or Capecitabine: LSMe

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Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 [C2D1: 0h, C3D1: 0h, C4D1: 0h]. Geometric Mean, ng/mL (Geometric Coefficient of Variation). 150mg Abemaciclib + 150mg LY3023414 (n=9): 27.3 (450).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose [C1D1: 2h Post dose]. Geometric Mean, ng/mL (Geometric Coefficient of Variation). 150mg Abemaciclib + 150mg LY3023414 (n=28): 518 (67).