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

NCT ID: NCT02079636

Last Updated: 2020-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-28
• Study Completion Date: 2019-08-29

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.

Conditions

Carcinoma, Non-small Cell Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Abemaciclib + Pemetrexed

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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

Pemetrexed

Intervention Type: DRUG

Administered IV

Abemaciclib + Gemcitabine

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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

Gemcitabine

Intervention Type: DRUG

Administered IV

Abemaciclib + Ramucirumab

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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

Ramucirumab

Intervention Type: DRUG

Administered IV

Abemaciclib + LY3023414

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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

LY3023414

Intervention Type: DRUG

Administered orally

Abemaciclib + Pembrolizumab

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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

Administered orally

Pembrolizumab

Intervention Type: DRUG

Administered IV

Interventions

Abemaciclib

Administered orally

Intervention Type: DRUG

Pemetrexed

Administered IV

Intervention Type: DRUG

Gemcitabine

Administered IV

Intervention Type: DRUG

Ramucirumab

Administered IV

Intervention Type: DRUG

LY3023414

Administered orally

Intervention Type: DRUG

Pembrolizumab

Administered IV

Intervention Type: DRUG

Other Intervention Names

LY2835219; Alimta; Gemzar; Cyramza; Keytruda

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.

• 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.

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

UCLA Department of Medicine-Hematology/Oncology

Los Angeles, California, United States

University of California, Davis - Health Systems

Sacramento, California, United States

Indiana Cancer Pavilion

Indianapolis, Indiana, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

The West Clinic

Germantown, Tennessee, United States

Hospital Universitario Ramon y Cajal

Madrid, , 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, , 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, , Spain

Countries

United States; Spain

References

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.

Reference Type: DERIVED

PMID: 30082474 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24919854 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

https://www.lillytrialguide.com/en-US/studies/non-small-cell-lung-cancer/JPBJ#?postal=

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)

Other Identifiers

I3Y-MC-JPBJ

Identifier Type: OTHER

Identifier Source: secondary_id

2013-004648-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KEYNOTE-238

Identifier Type: OTHER

Identifier Source: secondary_id

15266

Identifier Type: -

Identifier Source: org_study_id