Carcinoma, Non-small Cell LungPhase 1NCT02079636

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

A Phase 1 study testing Abemaciclib, Pemetrexed and Gemcitabine in people with Carcinoma, Non-small Cell Lung, run by Eli Lilly and Company at 11 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Carcinoma, Non-small Cell Lung
What is being tested?: Abemaciclib, Pemetrexed and Gemcitabine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 142 participants
Where: 11 sitesin 2 countries
Study dates: 28 Mar 2014to 29 Aug 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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.

Trial locations and contacts

11 sites in 2 countries.

Country

City, postcode or hospital

11 sites in 2 countries

United States8 sites

University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102
Carolinas Medical Center
Charlotte, North Carolina, 28204
Highlands Oncology Group
Fayetteville, Arkansas, 72703
The West Clinic
Germantown, Tennessee, 38138
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Indiana Cancer Pavilion
Indianapolis, Indiana, 46202
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, 90095
University of California, Davis - Health Systems
Sacramento, California, 95817

Other trials in United States

Spain3 sites

Hospital Universitario Ramon y Cajal
Madrid, 28034
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
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

Other trials in Spain

About this study

Official title: A Phase 1b Study of LY2835219 in Combination With Multiple Single Agent Options for Patients With Stage IV NSCLC

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.

Conditions: Carcinoma, Non-small Cell Lung
Being tested: Abemaciclib, Pemetrexed, Gemcitabine, Ramucirumab, LY3023414
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AbemaciclibDrug
Also called LY2835219
Administered orally
PemetrexedDrug
Also called Alimta
Administered IV
GemcitabineDrug
Also called Gemzar
Administered IV
RamucirumabDrug
Also called Cyramza
Administered IV
LY3023414Drug
Administered orally
PembrolizumabDrug
Also called Keytruda
Administered IV

Study groups in NCT02079636
Study group	Role	What they receive
Abemaciclib + Pemetrexed	Experimental	150 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. Receives: Drug: Abemaciclib; Drug: Pemetrexed
Abemaciclib + Gemcitabine	Experimental	150 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. Receives: Drug: Abemaciclib; Drug: Gemcitabine
Abemaciclib + Ramucirumab	Experimental	150 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. Receives: Drug: Abemaciclib; Drug: Ramucirumab
Abemaciclib + LY3023414	Experimental	100 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. Receives: Drug: Abemaciclib; Drug: LY3023414
Abemaciclib + Pembrolizumab	Experimental	100 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. Receives: Drug: Abemaciclib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
ORR is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Measured: Baseline through study completion (Up To 15 Months)
Progression Free Survival Time in Part A, B, C, D and E
Progression free survival (PFS) defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was 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 participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. PFS time was summarized using Kaplan-Meier estimates.
Measured: 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
The MDASI-LC is a self-reported lung cancer instrument included 22 items covered by one of the following dimensions: Mean core symptom severity (Core items 1-13: pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sad, vomiting, numbness/tingling), Lung cancer symptoms (3 items: coughing, constipation, sore throat), Mean symptom severity (13 core items plus 3 lung items) and Interference with mood or functional status (6 items: general activity, mood, work, relations with other people, walking, enjoyment of life). The mean of all symptom subscale items was calculated where 0 equals "not present" and 10 equals "as bad as you can imagine." A change from baseline with negative values indicate improvement, positive values indicate worsening.
Measured: 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
Cmax of Abemaciclib on day 1 and at steady State (Cycle 2 Day 1) Part A , B, C, D and E was evaluated.
Measured: 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
Cmax of pemetrexed at steady state in Part A was evaluated.
Measured: C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Dose-normalized Maximum Concentration (Cmax) of Active Gemcitabine Metabolite: 2',2'-Difluorodeoxyuridine (dFdU) on Day 1 and at Steady State (Cycle 2 Day 1) in Part B
Cmax of active gemcitabine metabolite (dFdU) on day 1 and at steady state (Cycle 2 Day 1) dose-normalized to 1250 mg/m^2 in Part B was evaluated.
Measured: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C
Cmax of ramucirumab at 1 hour post-end-of-Infusion in Part C was evaluated.
Measured: C1D1 and C2D1: 1 hour post-end-of-infusion
PK: Maximum Concentration (Cmax) of LY3023414 in Part D
Cmax of LY3023414 in Part D was evaluated.
Measured: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E
Area under the concentration time curve from zero to 8 hours AUC(0-8h) of abemaciclib in Part A, B, C, D and E was evaluated.
Measured: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of Pemetrexed at Steady State in Part A
Area under the plasma concentration versus time curve from time zero to infinity (AUC[0-∞]) of Pemetrexed in Part A was evaluated.
Measured: C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of Active Gemcitabine Metabolite: 2',2'-Difluorodeoxyuridine (dFdU) on Day 1 and at Steady State (Cycle 2 Day 1) in Part B
Area under the plasma concentration time curve from time zero to 12 hours (AUC[0-12h]) of active gemcitabine metabolite (dFdU) in Part B was evaluated
Measured: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D
Area under the plasma concentration versus time curve from time zero to infinity (AUC) of LY3023414 in Part D was evaluated. For Day 1, AUC is defined as AUC from time zero to infinity (AUC[0-∞]), for steady state, AUC is defined as AUC from time zero to the end of the dosing interval, tau (AUC[0-tau ])
Measured: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Mar 201429 Aug 2019

First posted6 Mar 2014 (estimated)
Study start28 Mar 2014
Primary completion2 May 2018
Study completion29 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Carcinoma, Non-small Cell LungStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 142 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02079636
Sponsor's protocol ID: 15266
Other IDs: I3Y-MC-JPBJ, 2013-004648-41, KEYNOTE-238
Status last verified: 15 Nov 2019
First submitted: 4 Mar 2014
Last updated: 11 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Expanded access: Available

Publications

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.
PubMed 30082474
Gelbert 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.
PubMed 24919854

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b Study of LY2835219 in Combination With Multiple Single Agent Options for Patients With Stage IV NSCLC
ClinicalTrials.gov ID: NCT02079636
Acronym / sponsor ID: 15266
Conditions: Carcinoma, Non-small Cell Lung
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 142 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Collaborators: Merck Sharp & Dohme LLC
Study start: 28 Mar 2014 (actual)
Primary completion: 2 May 2018 (actual)
Study completion: 29 Aug 2019 (actual)
First posted: 6 Mar 2014 (estimated)
Results: Posted 11 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Abemaciclib + Pemetrexed	Experimental	Drug: Abemaciclib, Drug: Pemetrexed150 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	Experimental	Drug: Abemaciclib, Drug: Gemcitabine150 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	Experimental	Drug: Abemaciclib, Drug: Ramucirumab150 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	Experimental	Drug: Abemaciclib, Drug: LY3023414100 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	Experimental	Drug: Abemaciclib, Drug: Pembrolizumab100 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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.

Key exclusion criteria (27 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AbemaciclibAlso: LY2835219Administered orally	Drug	Abemaciclib + Gemcitabine, Abemaciclib + LY3023414, Abemaciclib + Pembrolizumab, Abemaciclib + Pemetrexed, Abemaciclib + Ramucirumab
PemetrexedAlso: AlimtaAdministered IV	Drug	Abemaciclib + Pemetrexed
GemcitabineAlso: GemzarAdministered IV	Drug	Abemaciclib + Gemcitabine
RamucirumabAlso: CyramzaAdministered IV	Drug	Abemaciclib + Ramucirumab
LY3023414Administered orally	Drug	Abemaciclib + LY3023414
PembrolizumabAlso: KeytrudaAdministered IV	Drug	Abemaciclib + Pembrolizumab

Primary outcome

Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E
Time frame: Baseline through study completion (Up To 15 Months)
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.

12 secondary outcomes

Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E
Time frame: Baseline through study completion (Up To 15 Months)
Progression Free Survival Time in Part A, B, C, D and E
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Dose-normalized Maximum Concentration (Cmax) of Active Gemcitabine Metabolite: 2',2'-Difluorodeoxyuridine (dFdU) on Day 1 and at Steady State (Cycle 2 Day 1) in Part B
Time frame: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C
Time frame: C1D1 and C2D1: 1 hour post-end-of-infusion
PK: Maximum Concentration (Cmax) of LY3023414 in Part D
Time frame: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E
Time frame: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of Pemetrexed at Steady State in Part A
Time frame: C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of Active Gemcitabine Metabolite: 2',2'-Difluorodeoxyuridine (dFdU) on Day 1 and at Steady State (Cycle 2 Day 1) in Part B
Time frame: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D
Time frame: C1D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose; C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose

Results and safety

Results posted to the registry on 11 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: 150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed	8	5
Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed	15	13
Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine	3	3
Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine	21	9
Part C: 150 mg Abemaciclib + 10mg/kg Ramucirumab Day 1	4	2
Part C: 200 mg Abemaciclib + 10mg/kg Ramucirumab Day1	19	13
Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8	12	11
Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8	4	3
Part D: 100 mg Abemaciclib + 100 mg LY3023414	3	3
Part D: 150 mg Abemaciclib + 100 mg LY3023414	9	6
Part D: 150 mg Abemaciclib + 150 mg LY3023414	10	8
Part D: 200 mg Abemaciclib + 150 mg LY3023414	6	4
Part D: 150 mg Abemaciclib + 200 mg LY3023414	8	5
Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab	3	3
Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab	17	12

Primary outcome: Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E

Time frame: Baseline through study completion (Up To 15 Months). Count of participants. Unit: Participants

Measure	Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed n = 8	Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed n = 15	Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine n = 3	Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine n = 21	Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 n = 4	Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 n = 19	Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 n = 12	Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 n = 4	Part D: 100 mg Abemaciclib + 100 mg LY3023414 n = 3	Part D: 150 mg Abemaciclib + 100 mg LY3023414 n = 9	Part D: 150 mg Abemaciclib + 150 mg LY3023414 n = 10	Part D: 200 mg Abemaciclib + 150 mg LY3023414 n = 6	Part D: 150 mg Abemaciclib + 200 mg LY3023414 n = 8	Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab n = 3	Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab n = 17
Value	1	4	0	5	1	4	1	3	1	1	1	1	2	0	0

Population analysed: All randomized participants who received at least one dose of study drug in Part A, B, C, D and E.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 4 years and 1 Month. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A:150 mg Abemaciclib + 500 mg/m^2 Pemetrexed	4 of 8 (50%)	8 of 8 (100%)	2 of 8
Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed	8 of 15 (53.3%)	15 of 15 (100%)	1 of 15
Part B:150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3
Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine	10 of 21 (47.6%)	21 of 21 (100%)	6 of 21
Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Day1	3 of 4 (75%)	4 of 4 (100%)	2 of 4
Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day1	12 of 19 (63.2%)	19 of 19 (100%)	4 of 19
Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8	3 of 12 (25%)	12 of 12 (100%)	1 of 12
Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8	3 of 4 (75%)	4 of 4 (100%)	1 of 4
Part D: 100 mg Abemaciclib + 100 mg LY3023414	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Part D: 150 mg Abemaciclib + 100 mg LY3023414	2 of 9 (22.2%)	8 of 9 (88.9%)	1 of 9
Part D: 150 mg Abemaciclib + 150 mg LY3023414	3 of 10 (30%)	10 of 10 (100%)	0 of 10
Part D: 200 mg Abemaciclib + 150 mg LY3023414	0 of 6 (0%)	5 of 6 (83.3%)	1 of 6
Part D: 150 mg Abemaciclib + 200 mg LY3023414	4 of 8 (50%)	8 of 8 (100%)	1 of 8
Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab	9 of 17 (52.9%)	16 of 17 (94.1%)	2 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30082474Kim 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.
Derived from this study: PubMed 24919854Gelbert 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.
Click here for more information about this study: A Study of Abemaciclib (LY2835219) in Combination With Another Anti-cancer Drug in Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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) study director

Eli Lilly and Company

11 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Abemaciclib, Pemetrexed and Gemcitabine in people with Carcinoma, Non-small Cell Lung, run by Eli Lilly and Company at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E (time frame: Baseline through study completion (Up To 15 Months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02079636, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2020.