A Study of Abemaciclib (LY2835219) in Combination With Another Anti-cancer Drug in Participants With Lung Cancer (NSCLC)
A Phase 1b Study of LY2835219 in Combination With Multiple Single Agent Options for Patients With Stage IV NSCLC
4 other identifiers
interventional
142
2 countries
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2014
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 4, 2014
CompletedFirst Posted
Study publicly available on registry
March 6, 2014
CompletedStudy Start
First participant enrolled
March 28, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 2, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
August 29, 2019
CompletedResults Posted
Study results publicly available
September 11, 2020
CompletedSeptember 11, 2020
November 15, 2019
4.1 years
March 4, 2014
August 22, 2020
August 22, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E
A DLT defined as adverse event(AE) occurring between Day 1 and Day 21 of Cycle 1 that was considered at least possibly related to either abemaciclib or the combination therapy and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 \[NCI-CTCAE v 4.0\] \[NCI 2009\]):Grade(Gr)≥3 nonhematological toxicity,Gr4 thrombocytopenia lasting at least 5 days and/or complicated with bleeding,Gr≥3 febrile neutropenia(ntr) and for Part D participants (pts): Gr3 hyperglycemia (fasting) of \<5 days, Gr3 hypertriglyceridemia or hyperlipidemia without optimal treatment.A DLT-equivalent defined as AE that would have met the criteria for DLT if it had occurred during Cycle 1 for pts enrolled in dose-escalation phase,but that occurs between 1)Day 1 and Day 21 of Cycle 2 and beyond for a participant enrolled in dose-escalation phase 2) at any time for a participant in dose-expansion phase.
Baseline through study completion (Up To 15 Months)
Secondary Outcomes (12)
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E
Baseline through study completion (Up To 15 Months)
Progression Free Survival Time in Part A, B, C, D and E
Date of first dose until first documented progression or death (Up To 15 Months)
Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E
Baseline, through study completion (Up To 15 Months)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib on Day 1 and at Steady State (Cycle 2 Day 1) in Part A , B, C, D and E
Cycle 1 Day 1 (C1D1) pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; Cycle 2 Day 1 (C2D1) pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
Pharmacokinetics: Maximum Concentration (Cmax) of Pemetrexed at Steady State in Part A
C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
- +7 more secondary outcomes
Study Arms (5)
Abemaciclib + Pemetrexed
EXPERIMENTAL150 milligram (mg) or 200 mg 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
EXPERIMENTAL150 mg or 200 mg abemaciclib 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
EXPERIMENTAL150 mg or 200 mg 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
EXPERIMENTAL100 mg or 150 mg or 200 mg abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100, 150, or 200 mg 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
EXPERIMENTAL100 mg or 150 mg 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.
Interventions
Administered orally
Eligibility Criteria
You may qualify if:
- 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.
- +1 more criteria
You may not qualify if:
- 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.
- 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.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companylead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (11)
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, 90095, United States
University of California, Davis - Health Systems
Sacramento, California, 95817, United States
Indiana Cancer Pavilion
Indianapolis, Indiana, 46202, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Carolinas Medical Center
Charlotte, North Carolina, 28204, United States
The West Clinic
Germantown, Tennessee, 38138, United States
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Majadahonda, 28222, Spain
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Seville, 41013, Spain
Related Publications (2)
Kim ES, Kelly K, Paz-Ares LG, Garrido P, Jalal S, Mahadevan D, Gutierrez M, Provencio M, Schaefer E, Shaheen M, Johnston EL, Turner PK, Kambhampati SRP, Beckmann R, Hossain A, John WJ, Goldman JW. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non-Small Cell Lung Cancer: A Phase Ib Study. Clin Cancer Res. 2018 Nov 15;24(22):5543-5551. doi: 10.1158/1078-0432.CCR-18-0651. Epub 2018 Aug 6.
PMID: 30082474DERIVEDGelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.
PMID: 24919854DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- 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
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
March 4, 2014
First Posted
March 6, 2014
Study Start
March 28, 2014
Primary Completion
May 2, 2018
Study Completion
August 29, 2019
Last Updated
September 11, 2020
Results First Posted
September 11, 2020
Record last verified: 2019-11-15