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NCT02981342

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

Completed Phase 2 Results posted Last updated 20 November 2019
What this trial tests

Phase 2 trial testing Abemaciclib in Pancreatic Ductal Adenocarcinoma in 106 participants. Completed in 9 November 2018.

Timeline
12 January 2017
Primary endpoint
20 April 2018
9 November 2018

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment106
Start date12 January 2017
Primary completion20 April 2018
Estimated completion9 November 2018
Sites32 locations across France, Belgium, Taiwan, United Kingdom, Israel, Australia, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Pancreatic Ductal Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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 progres

GroupValue95% CI
200mg Abemaciclib15.22.9 – 27.4
150mg Abemaciclib + 150mg LY302341412.11.0 – 23.3
Gemcitabine or Capecitabine36.420 – 52.8
Stage 2: Progression Free Survival (PFS) Primary · Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)

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 no

GroupValue95% CI
200mg Abemaciclib1.681.35 – 1.84
150mg Abemaciclib + 150mg LY30234141.811.28 – 1.91
Gemcitabine or Capecitabine3.251.05 – 5.65
Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR Secondary · Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)

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.

GroupValue95% CI
200mg Abemaciclib30 – 8.9
150mg Abemaciclib + 150mg LY30234140NA – NA
Gemcitabine or Capecitabine30 – 8.9
Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) Secondary · Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose

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

Abemaciclib
GroupValue95% CI
150mg Abemaciclib + 150mg Galunisertib356± 137
LSN2839567 (M2)
GroupValue95% CI
150mg Abemaciclib + 150mg Galunisertib85.1± 66
LSN3106726 (M20)
GroupValue95% CI
150mg Abemaciclib + 150mg Galunisertib153± 58
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 Secondary · Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)

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 defi

GroupValue95% CI
200mg Abemaciclib30 – 8.9
150mg Abemaciclib + 150mg LY302341400 – 0
Gemcitabine or Capecitabine30 – 8.9
Stage 2: Overall Survival (OS) Secondary · Baseline to Death from Any Cause (Up to 10 Months)

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.

GroupValue95% CI
200mg Abemaciclib2.711.97 – 5.36
150mg Abemaciclib + 150mg LY30234143.291.97 – 5.03
Gemcitabine or CapecitabineNA2.53 – NA
Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level Secondary · Baseline, 6 Months

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.

GroupValue95% CI
200mg Abemaciclib4281.53± 8177.89
150mg Abemaciclib + 150mg LY30234143225.29± 5730.25
Gemcitabine or Capecitabine-501.17± 7198.70
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) Secondary · Baseline, 6 Months

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 completel

Pain at its Worst in Last 24 hours
GroupValue95% CI
200mg Abemaciclib0.63± 0.47
150mg Abemaciclib + 150mg LY3023414-0.33± 0.55
Gemcitabine or Capecitabine-0.02± 0.57
Pain at its Least in Last 24 hours
GroupValue95% CI
200mg Abemaciclib0.86± 0.42
150mg Abemaciclib + 150mg LY30234140.18± 0.49
Gemcitabine or Capecitabine0.39± 0.51
Pain on the Average
GroupValue95% CI
200mg Abemaciclib0.62± 0.45
150mg Abemaciclib + 150mg LY3023414-0.03± 0.51
Gemcitabine or Capecitabine-0.07± 0.53
Pain Right Now
GroupValue95% CI
200mg Abemaciclib0.38± 0.34
150mg Abemaciclib + 150mg LY30234140.34± 0.59
Gemcitabine or Capecitabine-0.38± 0.61
Pain Interfered General Activity
GroupValue95% CI
200mg Abemaciclib0.64± 0.47
150mg Abemaciclib + 150mg LY30234140.07± 0.55
Gemcitabine or Capecitabine0.22± 0.57
Pain Interfered with Mood
GroupValue95% CI
200mg Abemaciclib0.54± 0.41
150mg Abemaciclib + 150mg LY30234140.28± 0.48
Gemcitabine or Capecitabine0.60± 0.50
Pain Interfered Walking Ability
GroupValue95% CI
200mg Abemaciclib0.05± 0.55
150mg Abemaciclib + 150mg LY30234140.83± 0.64
Gemcitabine or Capecitabine0.19± 0.67
Pain Interfered with Normal Work
GroupValue95% CI
200mg Abemaciclib1.07± 0.51
150mg Abemaciclib + 150mg LY30234140.66± 0.59
Gemcitabine or Capecitabine0.19± 0.61
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) Secondary · Baseline, 6 Months

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

Global Health Status
GroupValue95% CI
200mg Abemaciclib-6.21± 3.87
150mg Abemaciclib + 150mg LY3023414-4.82± 4.50
Gemcitabine or Capecitabine-2.40± 4.64
Functional Scales: Physical Functioning
GroupValue95% CI
200mg Abemaciclib-14.44± 4.40
150mg Abemaciclib + 150mg LY3023414-11.65± 5.12
Gemcitabine or Capecitabine-5.42± 5.12
Functional Scales: Role Functioning
GroupValue95% CI
200mg Abemaciclib-17.09± 6.17
150mg Abemaciclib + 150mg LY3023414-18.05± 7.32
Gemcitabine or Capecitabine-17.10± 7.36
Functional Scales: Emotional Functioning
GroupValue95% CI
200mg Abemaciclib-4.89± 4.49
150mg Abemaciclib + 150mg LY3023414-0.63± 5.22
Gemcitabine or Capecitabine2.06± 5.41
Functional Scales: Cognitive Functioning
GroupValue95% CI
200mg Abemaciclib-10.43± 4.10
150mg Abemaciclib + 150mg LY3023414-8.39± 4.77
Gemcitabine or Capecitabine-5.18± 4.95
Functional Scale: Social Functioning
GroupValue95% CI
200mg Abemaciclib-21.12± 4.90
150mg Abemaciclib + 150mg LY3023414-17.09± 5.72
Gemcitabine or Capecitabine-2.00± 5.95
Symptom Scales: Fatigue
GroupValue95% CI
200mg Abemaciclib14.13± 4.92
150mg Abemaciclib + 150mg LY302341414.90± 5.73
Gemcitabine or Capecitabine5.64± 5.71
Symptom Scales: Nausea and Vomiting
GroupValue95% CI
200mg Abemaciclib7.98± 5.57
150mg Abemaciclib + 150mg LY30234149.42± 6.47
Gemcitabine or Capecitabine11.88± 6.50
Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 Secondary · C2D1: 0h, C3D1: 0h, C4D1: 0h

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

GroupValue95% CI
150mg Abemaciclib + 150mg LY302341427.3± 450
Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose Secondary · C1D1: 2h Post dose

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

GroupValue95% CI
150mg Abemaciclib + 150mg LY3023414518± 67

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 30 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

150mg Abemaciclib + 150mg Galunisertib (Safety Lead - In)
Serious: 4/7 (57%)
Deaths: 5/7
200mg Abemaciclib
Serious: 17/32 (53%)
Deaths: 22/32
150mg Abemaciclib + 150mg LY3023414
Serious: 18/33 (55%)
Deaths: 21/33
Gemcitabine or Capecitabine
Serious: 15/26 (58%)
Deaths: 12/26

Serious adverse events (62 terms)

ReactionSystem150mg Abemaciclib + 150mg …200mg Abemaciclib150mg Abemaciclib + 150mg …Gemcitabine or Capecitabine
VomitingGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
StomatitisGastrointestinal disorders
PyrexiaGeneral disorders
Bile duct obstructionHepatobiliary disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
AscitesGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Duodenal stenosisGastrointestinal disorders
Gastric ulcer haemorrhageGastrointestinal disorders
Gastrointestinal perforationGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
Obstruction gastricGastrointestinal disorders
OesophagitisGastrointestinal disorders
SubileusGastrointestinal disorders
AstheniaGeneral disorders
ChillsGeneral disorders
FatigueGeneral disorders
General physical health deteriorationGeneral disorders
Other adverse events (104 terms — click to expand)

ReactionSystem150mg Abemaciclib + 150mg …200mg Abemaciclib150mg Abemaciclib + 150mg …Gemcitabine or Capecitabine
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
StomatitisGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
AstheniaGeneral disorders
Bile duct obstructionHepatobiliary disorders
Alanine aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
White blood cell count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
General physical health deteriorationGeneral disorders
Aspartate aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
Weight decreasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Confusional statePsychiatric disorders
Acute kidney injuryRenal and urinary disorders
Rash maculo-papularSkin and subcutaneous tissue disorders

Most-reported serious reactions: Vomiting, Thrombocytopenia, Abdominal pain, Stomatitis, Pyrexia, Bile duct obstruction, Pulmonary embolism, Anaemia.

Data from ClinicalTrials.gov NCT02981342 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
    Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
  2. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
    Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
  3. CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought.
    Klein ME, Kovatcheva M, Davis LE, Tap WD, et al · · 2018 · cited 308× · PMID 29731395 · DOI 10.1016/j.ccell.2018.03.023
  4. Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma.
    Qian Y, Gong Y, Fan Z, Luo G, et al · · 2020 · cited 231× · PMID 33008426 · DOI 10.1186/s13045-020-00958-3
  5. Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma.
    Daniel SK, Sullivan KM, Labadie KP, Pillarisetty VG. · · 2019 · cited 148× · PMID 30931508 · DOI 10.1186/s40169-019-0226-9
  6. Combination Therapies with CDK4/6 Inhibitors to Treat KRAS-Mutant Pancreatic Cancer.
    Goodwin CM, Waters AM, Klomp JE, Javaid S, et al · · 2023 · cited 125× · PMID 36346366 · DOI 10.1158/0008-5472.can-22-0391
  7. TAMing pancreatic cancer: combat with a double edged sword.
    Lankadasari MB, Mukhopadhyay P, Mohammed S, Harikumar KB. · · 2019 · cited 84× · PMID 30925924 · DOI 10.1186/s12943-019-0966-6
  8. Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Therapeutic Opportunities and Clinical Challenges.
    Poh AR, Ernst M. · · 2021 · cited 79× · PMID 34201127 · DOI 10.3390/cancers13122860

Verify or expand the search:

Other trials of Abemaciclib

Trials testing the same drug.

Other recruiting trials for Pancreatic Ductal Adenocarcinoma

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Other Eli Lilly and Company trials

Trials by the same sponsor.

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Data sources for this page

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