Carcinoma, Non-small Cell Lung
Conditions
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.
Interventions
DRUGAbemaciclib
Administered orally
DRUGPemetrexed
Administered IV
DRUGGemcitabine
Administered IV
DRUGRamucirumab
Administered IV
DRUGLY3023414
Administered orally
DRUGPembrolizumab
Administered IV
Sponsors
Merck Sharp & Dohme LLC
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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 | Cmax of Abemaciclib on day 1 and at steady State (Cycle 2 Day 1) Part A , B, C, D and E was evaluated. |
| 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 | Cmax of pemetrexed at steady state in Part A was evaluated. |
| 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 | 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 | 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. |
| PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C1D1 and C2D1: 1 hour post-end-of-infusion | Cmax of ramucirumab at 1 hour post-end-of-Infusion in Part C was evaluated. |
| PK: Maximum Concentration (Cmax) of LY3023414 in Part D | 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 | Cmax of LY3023414 in Part D was evaluated. |
| PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | 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 | 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. |
| PK: Area Under the Concentration Curve (AUC) of Pemetrexed at Steady State in Part A | C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose | Area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]) of Pemetrexed in Part A was evaluated. |
| 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 | 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 | 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 |
| PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | 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 | 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\[0-tau \]) |
Countries
Spain, United States
Participant flow
Pre-assignment details
Completers include participants who had cycle 1 and had received greater than or equal to (\>=) 75% of Abemaciclib drug in cycle 1.
Participants by arm
| Arm | Count |
|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed 150 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. | 8 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed 200 mg abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 500 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. | 15 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine 150 mg abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 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. | 3 |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine 200 mg abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 1250 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. | 21 |
| Part C:150 mg Abemaciclib+10mg/kg Ramucirumab Day1 150 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 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 4 |
| Part C: 200 mg Abemaciclib + 10mg/kg Ramucirumab Day1 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 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 19 |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 150 mg abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 8 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. | 12 |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 150 mg abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 10 mg/kg ramucirumab given intravenously over approximately 60 minutes on on Days 1 and 8 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 4 |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 100 mg Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100 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. | 3 |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 150 mg Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 100 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. | 9 |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 150 mg Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 150 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. | 10 |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 200 mg Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 150 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. | 6 |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 150 mg Abemaciclib given orally every 12 hours on Days 1 through 21 of a 21-day cycle in combination with 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. | 8 |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab 100 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. | 3 |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab 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. | 17 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 1 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 2 | 1 | 0 | 5 | 1 | 2 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive disease | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 4 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 1 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Total | Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Part C: 200 mg Abemaciclib + 10mg/kg Ramucirumab Day1 | Part C:150 mg Abemaciclib+10mg/kg Ramucirumab Day1 | Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.88 years STANDARD_DEVIATION 7.61 | 62.89 years STANDARD_DEVIATION 9.3 | 59.76 years STANDARD_DEVIATION 9.94 | 67.33 years STANDARD_DEVIATION 3.51 | 60.38 years STANDARD_DEVIATION 10.2 | 65.50 years STANDARD_DEVIATION 7.48 | 64.00 years STANDARD_DEVIATION 8.41 | 57.56 years STANDARD_DEVIATION 8.26 | 67.00 years STANDARD_DEVIATION 9.54 | 67.75 years STANDARD_DEVIATION 4.92 | 63.75 years STANDARD_DEVIATION 6.77 | 66.11 years STANDARD_DEVIATION 9.31 | 61.25 years STANDARD_DEVIATION 14.24 | 63.14 years STANDARD_DEVIATION 10.07 | 55.00 years STANDARD_DEVIATION 8.66 | 62.53 years STANDARD_DEVIATION 11.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 133 Participants | 17 Participants | 3 Participants | 7 Participants | 5 Participants | 10 Participants | 9 Participants | 3 Participants | 4 Participants | 11 Participants | 17 Participants | 4 Participants | 20 Participants | 2 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 7 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 128 Participants | 16 Participants | 3 Participants | 7 Participants | 5 Participants | 10 Participants | 7 Participants | 2 Participants | 4 Participants | 12 Participants | 18 Participants | 4 Participants | 16 Participants | 3 Participants | 13 Participants |
| Region of Enrollment Spain | 2 Participants | 45 Participants | 14 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 6 Participants | 4 Participants | 0 Participants | 5 Participants | 1 Participants | 7 Participants |
| Region of Enrollment United States | 6 Participants | 97 Participants | 3 Participants | 0 Participants | 8 Participants | 6 Participants | 10 Participants | 9 Participants | 3 Participants | 1 Participants | 6 Participants | 15 Participants | 4 Participants | 16 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 63 Participants | 10 Participants | 1 Participants | 5 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 0 Participants | 4 Participants | 10 Participants | 2 Participants | 11 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 79 Participants | 7 Participants | 2 Participants | 3 Participants | 4 Participants | 7 Participants | 4 Participants | 2 Participants | 4 Participants | 8 Participants | 9 Participants | 2 Participants | 10 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 8 | 1 / 15 | 1 / 3 | 6 / 21 | 2 / 4 | 4 / 19 | 1 / 12 | 1 / 4 | 0 / 3 | 1 / 9 | 0 / 10 | 1 / 6 | 1 / 8 | 0 / 3 | 2 / 17 |
| other Total, other adverse events | 8 / 8 | 15 / 15 | 3 / 3 | 21 / 21 | 4 / 4 | 19 / 19 | 12 / 12 | 4 / 4 | 3 / 3 | 8 / 9 | 10 / 10 | 5 / 6 | 8 / 8 | 3 / 3 | 16 / 17 |
| serious Total, serious adverse events | 4 / 8 | 8 / 15 | 1 / 3 | 10 / 21 | 3 / 4 | 12 / 19 | 3 / 12 | 3 / 4 | 1 / 3 | 2 / 9 | 3 / 10 | 0 / 6 | 4 / 8 | 0 / 3 | 9 / 17 |
Outcome results
Primary
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.
Time frame: Baseline through study completion (Up To 15 Months)
Population: All randomized participants who received at least one dose of study drug in Part A, B, C, D and E.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 4 Participants |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 0 Participants |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 5 Participants |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 4 Participants |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 3 Participants |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 1 Participants |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 2 Participants |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 0 Participants |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E | 0 Participants |
Secondary
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.
Time frame: Baseline, through study completion (Up To 15 Months)
Population: All randomized participants for cycles which at least 25% of participants in each arm have a score. MDASI-LC population included all randomized participants who completed at least 1 baseline assessment followed by at least 1 MDASI-LC result in Part A, B, C, D and E.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 1.22 units on a scale |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -0.05 units on a scale |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 2.32 units on a scale |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -0.16 units on a scale |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 0.89 units on a scale |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 0.71 units on a scale |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 0.83 units on a scale |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 0.49 units on a scale |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 1.67 units on a scale |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 0.00 units on a scale |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -0.44 units on a scale |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -0.54 units on a scale |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 0.95 units on a scale |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -0.08 units on a scale |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -0.03 units on a scale |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 0.19 units on a scale |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | -1.33 units on a scale |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -0.35 units on a scale |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | -0.67 units on a scale |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -0.41 units on a scale |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 0.72 units on a scale |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 0.61 units on a scale |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 0.15 units on a scale |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 1.13 units on a scale |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | -0.78 units on a scale |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -0.61 units on a scale |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | -1.00 units on a scale |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -0.64 units on a scale |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | -3.08 units on a scale |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -1.39 units on a scale |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -1.01 units on a scale |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 3.01 units on a scale |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 0.64 units on a scale |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 0.61 units on a scale |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 0.78 units on a scale |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 0.72 units on a scale |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 1.47 units on a scale |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 1.86 units on a scale |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 1.40 units on a scale |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 1.89 units on a scale |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 2.19 units on a scale |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 1.81 units on a scale |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 1.60 units on a scale |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 1.60 units on a scale |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | -0.73 units on a scale |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | -0.44 units on a scale |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | -0.22 units on a scale |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | -0.80 units on a scale |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 0.28 units on a scale |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | -0.38 units on a scale |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 0.67 units on a scale |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 0.19 units on a scale |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 0.91 units on a scale |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 0.99 units on a scale |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 1.67 units on a scale |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 1.44 units on a scale |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean symptom severity | 0.75 units on a scale |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean interference severity | 1.00 units on a scale |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean lung cancer symptom | 0.23 units on a scale |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E | Mean core symptom severity | 0.88 units on a scale |
Secondary
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.
Time frame: Baseline through study completion (Up To 15 Months)
Population: All randomized participants who received at least one dose of study drug in Part A, B, C, D and E.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 1 Participants |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 1 Participants |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 1 Participants |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 1 Participants |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 1 Participants |
| Part D: 200 mg Abemaciclib + 150 mg LY3023414 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part D: 150 mg Abemaciclib + 200 mg LY3023414 | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part E: 100 mg Abemaciclib + 200 mg Pembrolizumab | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 0 Participants |
| Part E: 150 mg Abemaciclib + 200 mg Pembrolizumab | Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E | 2 Participants |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of Pemetrexed at Steady State in Part A
Cmax of pemetrexed at steady state in Part A was evaluated.
Time frame: C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Pharmacokinetics: Maximum Concentration (Cmax) of Pemetrexed at Steady State in Part A | 98.1 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 29 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Pharmacokinetics: Maximum Concentration (Cmax) of Pemetrexed at Steady State in Part A | 93.5 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 30 |
Secondary
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.
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
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part A , B, C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Day 1 | 114 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67.4 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Steady State | NA nanograms per milliliter (ng/mL) | — |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Steady State | 509 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.5 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Day 1 | 212 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 79.8 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Day 1 | 80.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 14.7 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Steady State | NA nanograms per milliliter (ng/mL) | — |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Day 1 | 201 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71.7 |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Steady State | 417 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 77.7 |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | 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 | Day 1 | 140 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 95.7 |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | 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 | Steady State | 322 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 112 |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | 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 | Steady State | 228 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 152 |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | 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 | Day 1 | 195 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 85.8 |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | 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 | Steady State | 227 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 85.1 |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | 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 | Day 1 | 86.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 91.1 |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | 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 | Day 1 | 159 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.1 |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | 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 | Steady State | 305 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55.8 |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | 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 | Day 1 | 225 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103 |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | 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 | Day 1 | 125 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.2 |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | 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 | Steady State | 270 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.7 |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | 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 | Steady State | 240 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 87.5 |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | 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 | Day 1 | 114 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68.8 |
Secondary
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.
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
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part A, B, C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 533 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 69.6 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | NA nanogram*hour/mL (ng*h/mL) | — |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 979 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 77.5 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | 3710 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 41.1 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | NA nanogram*hour/mL (ng*h/mL) | — |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 393 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 31 |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 886 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 53.4 |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | 2690 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 53.4 |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 797 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 69 |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | 1720 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 119 |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 1030 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 127 |
| Part C: 200 mg Abemaciclib + 10 mg/kg Ramucirumab Day 1 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | 1840 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 115 |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 394 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 71.7 |
| Part C: 150 mg Abemaciclib + 8 mg/kg Ramucirumab Days 1 and 8 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | NA nanogram*hour/mL (ng*h/mL) | — |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | 1550 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 83.7 |
| Part C: 150 mg Abemaciclib + 10 mg/kg Ramucirumab Days 1 and 8 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 719 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 77.3 |
| Part D: 100 mg Abemaciclib + 100 mg LY3023414 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 967 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 139 |
| Part D: 150 mg Abemaciclib + 100 mg LY3023414 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | NA nanogram*hour/mL (ng*h/mL) | — |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Steady State | 1400 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 184 |
| Part D: 150 mg Abemaciclib + 150 mg LY3023414 | PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E | Day 1 | 518 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 21.6 |
Secondary
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
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
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part B.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Day 1 | 175000 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 16 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Steady State | NA nanogram*hour/mL (ng*h/mL) | — |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Day 1 | 246000 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 29 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Steady State | 208000 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 20 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Day 1 | 198000 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 26 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Steady State | 210000 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 23 |
Secondary
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\[0-tau \])
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
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part D.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | Day 1 | 1005 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 63 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | Steady State | 1303 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 64 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | Day 1 | 1751 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 56 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | Steady State | 1293 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 49 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | Day 1 | 3809 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 95 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D | Steady State | NA nanogram*hour/mL (ng*h/mL) | — |
Secondary
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.
Time frame: C2D1 pre-dose and 1, 2, 4, 6, 8, 10 h post-dose
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part A.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of Pemetrexed at Steady State in Part A | 201 microgram*hour per milliliter (μg*hr/mL) | Geometric Coefficient of Variation 30 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Area Under the Concentration Curve (AUC) of Pemetrexed at Steady State in Part A | 198 microgram*hour per milliliter (μg*hr/mL) | Geometric Coefficient of Variation 32 |
Secondary
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.
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
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part B.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Day 1 | 35600 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 14 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Steady State | NA nanogram per milliliter (ng/mL) | — |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Day 1 | 49600 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | 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 | Steady State | 38700 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Day 1 | 41900 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | 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 | Steady State | 35800 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
Secondary
PK: Maximum Concentration (Cmax) of LY3023414 in Part D
Cmax of LY3023414 in Part D was evaluated.
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
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part D.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of LY3023414 in Part D | Day 1 | 298 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 104 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of LY3023414 in Part D | Steady State | 438 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of LY3023414 in Part D | Day 1 | 454 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 81 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of LY3023414 in Part D | Steady State | 491 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Maximum Concentration (Cmax) of LY3023414 in Part D | Day 1 | 578 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 119 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Maximum Concentration (Cmax) of LY3023414 in Part D | Steady State | NA nanograms per milliliter (ng/mL) | — |
Secondary
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.
Time frame: C1D1 and C2D1: 1 hour post-end-of-infusion
Population: All randomized participants who received at least one dose of study drug with evaluable PK data in Part C.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C1D1 | 174 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 19.6 |
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C2D1 | 221 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 15 |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C2D1 | NA microgram per milliliter (μg/mL) | — |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C1D1 | 226 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 10 |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C2D1 | NA microgram per milliliter (μg/mL) | — |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C1D1 | 193 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 27 |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C2D1 | 226 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 32.3 |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C | C1D1 | 221 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 30.6 |
Secondary
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.
Time frame: Date of first dose until first documented progression or death (Up To 15 Months)
Population: All randomized participants in Part A, B, C, D and E. Censored participants: Part A= 13, Part B = 7, Part C = 17, Part D = 19, Part E = 10.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A:150 Milligram(mg) Abemaciclib + 500 mg/m^2 Pemetrexed | Progression Free Survival Time in Part A, B, C, D and E | 5.55 Months |
| Part A: 200 mg Abemaciclib + 500 mg/m^2 Pemetrexed | Progression Free Survival Time in Part A, B, C, D and E | 1.58 Months |
| Part B: 150 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Progression Free Survival Time in Part A, B, C, D and E | 4.83 Months |
| Part B: 200 mg Abemaciclib + 1250 mg/m^2 Gemcitabine | Progression Free Survival Time in Part A, B, C, D and E | 1.87 Months |
| Part C:150 mg Abemaciclib+10 mg/kg Ramucirumab Day 1 | Progression Free Survival Time in Part A, B, C, D and E | 4.11 Months |