A Study of Abemaciclib (LY2835219) in Combination With Another Anti-cancer Drug in Participants With Lung Cancer (NSCLC)

ID: NCT02079636
Status: Recruiting
Phase: Phase 1
Start Date: March 01, 2014
First Submitted: March 04, 2014
Last Updated: February 14, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company, Merck Sharp & Dohme Corp.
Location: Spain, United States
Conditions: Carcinoma, Non-small Cell Lung
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Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of abemaciclib in combination with another anti-cancer drug in participants with NSCLC that is advanced or has spread to other parts of the body (stage IV). The study will also investigate how the body processes the combination treatment and how the study drug affects the body. The study will also collect disease-related symptoms and participant-reported pain related to NSCLC.

Detailed Description

Condition or disease Intervention/treatment Phase

Carcinoma, Non-small Cell Lung

Drug: Abemaciclib
Other Names
LY2835219
Drug: Pemetrexed
Other Names
Alimta
Drug: Gemcitabine
Other Names
Gemzar
Drug: Ramucirumab
Other Names
Cyramza
Drug: LY3023414
Other Names
Drug: Pembrolizumab
Other Names
Phase 1

Tracking Information

First Submitted DateMarch 04, 2014
Last Update Posted DateFebruary 14, 2018
Start DateMarch 01, 2014
Anticipated Completion DateNovember 01, 2018
Primary Completion DateMay 01, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Number of Participants with One or More Drug Related Adverse Events [Time Frame: Baseline through study completion (15 months)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Pharmacokinetics: Maximum Concentration (Cmax) of Abemaciclib, Pemetrexed, Gemcitabine, Ramucirumab, and LY3023414 [Time Frame: Baseline through study completion (15 months)]

  • Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate) [Time Frame: Baseline through study completion (15 months)]

  • Progression Free Survival Time [Time Frame: Date of first dose until first documented progression or death (15 months)]

  • Change from Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) [Time Frame: Baseline, through study completion (15 months)]

  • Pharmacokinetics: Area Under the Concentration Curve (AUC) of Abemaciclib, Pemetrexed, Gemcitabine, Ramucirumab, and LY3023414 [Time Frame: Baseline through study completion (15 months)]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Abemaciclib (LY2835219) in Combination With Another Anti-cancer Drug in Participants With Lung Cancer (NSCLC)
Official TitleA Phase 1b Study of LY2835219 in Combination With Multiple Single Agent Options for Patients With Stage IV NSCLC
Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of abemaciclib in combination with another anti-cancer drug in participants with NSCLC that is advanced or has spread to other parts of the body (stage IV). The study will also investigate how the body processes the combination treatment and how the study drug affects the body. The study will also collect disease-related symptoms and participant-reported pain related to NSCLC.

Detailed Description

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
150
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Carcinoma, Non-small Cell Lung
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Abemaciclib

Administered orally

Other Names
LY2835219
Drug: Pemetrexed

Administered IV

Other Names
Alimta
Drug: Gemcitabine

Administered IV

Other Names
Gemzar
Drug: Ramucirumab

Administered IV

Other Names
Cyramza
Drug: LY3023414

Administered orally

Other Names
Drug: Pembrolizumab

Administered IV

Other Names
Study Groups/Cohorts
Abemaciclib + Pemetrexed
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 500 milligrams/square meter (mg/m^2) pemetrexed given intravenously (IV) over approximately 10 minutes on Day 1 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib + Gemcitabine
Abemacicilib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 milligram/square meter (mg/m^2) gemcitabine given intravenously over approximately 30 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib + Ramucirumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Day 1 or 8 to 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib + LY3023414
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100, 150, or 200mg LY3023414 given orally every 12 hours on Days 1 through 21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Abemaciclib + Pembrolizumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 200 mg pembrolizumab given intravenously over approximately 30 minutes on day 1 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Study Arms
Experimental Abemaciclib + Gemcitabine
Abemacicilib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 milligram/square meter (mg/m^2) gemcitabine given intravenously over approximately 30 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Gemcitabine
Abemacicilib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 milligram/square meter (mg/m^2) gemcitabine given intravenously over approximately 30 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Administered IV

Experimental Abemaciclib + LY3023414
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100, 150, or 200mg LY3023414 given orally every 12 hours on Days 1 through 21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : LY3023414
Administered orally

Experimental Abemaciclib + LY3023414
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100, 150, or 200mg LY3023414 given orally every 12 hours on Days 1 through 21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Pembrolizumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 200 mg pembrolizumab given intravenously over approximately 30 minutes on day 1 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Pembrolizumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 200 mg pembrolizumab given intravenously over approximately 30 minutes on day 1 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Pembrolizumab
Administered IV

Experimental Abemaciclib + Pemetrexed
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 500 milligrams/square meter (mg/m^2) pemetrexed given intravenously (IV) over approximately 10 minutes on Day 1 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Pemetrexed
Administered IV

Experimental Abemaciclib + Pemetrexed
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 500 milligrams/square meter (mg/m^2) pemetrexed given intravenously (IV) over approximately 10 minutes on Day 1 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Ramucirumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Day 1 or 8 to 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Ramucirumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Day 1 or 8 to 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Ramucirumab
Administered IV

Arm Intervention/Treatment
Experimental Abemaciclib + Gemcitabine
Abemacicilib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 milligram/square meter (mg/m^2) gemcitabine given intravenously over approximately 30 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Abemaciclib + Gemcitabine
Abemacicilib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 milligram/square meter (mg/m^2) gemcitabine given intravenously over approximately 30 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Experimental Abemaciclib + LY3023414
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100, 150, or 200mg LY3023414 given orally every 12 hours on Days 1 through 21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : LY3023414
Experimental Abemaciclib + LY3023414
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100, 150, or 200mg LY3023414 given orally every 12 hours on Days 1 through 21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Abemaciclib + Pembrolizumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 200 mg pembrolizumab given intravenously over approximately 30 minutes on day 1 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Abemaciclib + Pembrolizumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 200 mg pembrolizumab given intravenously over approximately 30 minutes on day 1 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Pembrolizumab
Experimental Abemaciclib + Pemetrexed
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 500 milligrams/square meter (mg/m^2) pemetrexed given intravenously (IV) over approximately 10 minutes on Day 1 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Pemetrexed
Experimental Abemaciclib + Pemetrexed
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 500 milligrams/square meter (mg/m^2) pemetrexed given intravenously (IV) over approximately 10 minutes on Day 1 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Abemaciclib + Ramucirumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Day 1 or 8 to 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Abemaciclib + Ramucirumab
Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Day 1 or 8 to 10 milligram/kilogram (mg/kg) ramucirumab given intravenously over approximately 60 minutes on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Ramucirumab

Recruitment Information

Recruitment Status:Recruiting
Enrollment150
Completion DateNovember 01, 2018
Eligibility Criteria: Inclusion Criteria:
- For all Parts: The participant must have stage IV non-small cell lung cancer (NSCLC).
- For Part A (abemaciclib + pemetrexed): Non-squamous subtypes only. The participant must have received at least one but no more than three prior therapies for advanced/metastatic NSCLC.
- For Part B (abemaciclib + gemcitabine): Any subtype. The participant must have received at least one but not more than three prior therapies for advanced/metastatic NSCLC.
- For Part C (abemaciclib + ramucirumab): Any subtype. The participant must have received at least two but not more than three prior therapies for advanced/metastatic NSCLC.
- For Part D (abemaciclib + LY3023414): Any subtype. The participant must have received at least two, but not more than three prior therapies for advanced/metastatic NSCLC. The participant must not have received prior treatment with any phosphoinositide 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitor.
- For Part E (abemaciclib + pembrolizumab): Any subtype. The participant must have received at least one but no more than three prior therapies for advanced/metastatic NSCLC.
- Have either measureable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
- Have adequate organ function including:
- Hematologic: Absolute neutrophil count (ANC) 1.5 x 109/liter (L), platelets 100 x 109/L, and hemoglobin 8 gram/deciliter (g/dL).
- Hepatic: Bilirubin 1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT) and aspartate transaminase (AST) 3.0 times ULN. For participants with tumor involvement of the liver, AST and ALT equaling ≤5.0 times ULN are acceptable. Alkaline phosphatase ≤5.0 times ULN for participants with tumor involvement of the bone is acceptable.
- Renal: Serum creatinine 1.5 times ULN.
- Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia.
- Male and female participants of reproductive potential must agree to use medically approved contraceptive precautions during the trial and 3 to 4 months (as appropriate) following last dose of study drug.
- Have an estimated life expectancy of ≥12 weeks.
- Are able to swallow oral medications.

Exclusion Criteria:
- Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment are eligible.
- Parts A, B, D and E: Have central nervous system (CNS) metastasis with development of associated neurological changes 14 days prior to receiving study drug.
- Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix or breast), unless in complete remission with no therapy for a minimum of 3 years.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 3 to 4 months after the last dose of trial treatment (as appropriate).
- Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen [HBSAg], or hepatitis C antibodies). Screening is not required for enrollment.
- Parts A, B, C, and E: Have QTc interval of > 470 millisecond (msec) on screening electrocardiogram (ECG). Part D participants have QTc interval of >450msec on screening ECG.
Additional
Exclusion Criteria For Part C
- History or evidence of cardiovascular risk including any of the following:
- History of acute coronary syndromes (including myocardial infarction and angina), coronary angioplasty, or stenting within 6 months prior to enrollment.
- History or evidence of current ≥Class II congestive heart failure as defined by New York Heart Association.
- Treatment refractory hypertension defined as a blood pressure of systolic >140 millimeter of mercury (mmHg) and/or diastolic >90 mmHg which cannot be controlled by antihypertensive therapy.
- Participants with intracardiac defibrillators.
- History or evidence of CNS disease. Radiographic screening of all participants without history of CNS metastasis is required.
- Radiographically documented evidence of major vessel invasion or encasement by cancer.
- Uncontrolled thromboembolic or hemorrhagic disorders.
- Participants receiving daily treatment with aspirin >325mg/day or other known inhibitors of platelet function.
- History of gross hemoptysis within 2 months of study entry.
- Evidence of nonhealing wounds, ulcers, or bone fractures within 28 days prior to study entry.
- Undergone major surgery within 28 days prior to first dose of study drug or have subcutaneous venous access device placement within 7 days prior to first dose.
Additional
Exclusion Criteria For Part D
- Have insulin-dependent diabetes mellitus or a history of gestational diabetes mellitus.
- Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetic agents as documented by hemoglobin A1c (HbA1c) <7%.
- History or evidence of cardiovascular risk including any of the following -- History of acute coronary syndromes (including myocardial infarction and angina), coronary angioplasty, or stenting within 6 months prior to enrollment.
Additional
Exclusion Criteria for Part E
- Received prior monoclonal antibody (mAb) within 4 weeks prior to study.
- Has active autoimmune disease that has required treatment in the past 2 years.
- Has history of interstitial lung disease or pneumonitis.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Spain
United States

Administrative Information

NCT Number:NCT02079636
Other Study ID Numbers
15266
I3Y-MC-JPBJ
2013-004648-41
KEYNOTE-238
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company