Phase 1
Completed N=142
A Study of Abemaciclib (LY2835219) in Combination With Another Anti-cancer Drug in Participants With Lung Cancer (NSCLC)
Source: ClinicalTrials.gov NCT02079636 ↗Enrolled (actual)
142
Serious AEs
44.4%
Results posted
Sep 2020
Primary outcomePrimary: Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E — 1; 4; 0; 5 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicities (DLT) or DLT-equivalent in Part A, B, C, D and E |
1; 4; 0; 5; 1; 4 | — |
| SECONDARY Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) in Part A, B, C, D and E |
0; 1; 0; 1; 1; 1 | — |
| SECONDARY Progression Free Survival Time in Part A, B, C, D and E |
5.55; 1.58; 4.83; 1.87; 4.11 | — |
| SECONDARY Change From Baseline in MD Anderson Symptom Inventory Scale-Lung Cancer (MDASI-LC) in Part A, B, C, D and E |
-0.16; 0.89; -0.54; -0.08; -0.35; 0.61 | — |
| 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 |
114; 212; 80.6; 201; 140; 195 | — |
| SECONDARY Pharmacokinetics: Maximum Concentration (Cmax) of Pemetrexed at Steady State in Part A |
98.1; 93.5 | — |
| 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 |
35600; 49600; 41900; NA; 38700; 35800 | — |
| SECONDARY PK: Maximum Concentration (Cmax) of Ramucirumab at 1 Hour Post-End-of-Infusion in Part C |
174; 226; 193; 221; 221; NA | — |
| SECONDARY PK: Maximum Concentration (Cmax) of LY3023414 in Part D |
298; 454; 578; 438; 491; NA | — |
| SECONDARY PK: Area Under the Concentration Curve (AUC) of Abemaciclib in Part A, B, C, D and E |
533; 979; 393; 886; 797; 1030 | — |
| SECONDARY PK: Area Under the Concentration Curve (AUC) of Pemetrexed at Steady State in Part A |
201; 198 | — |
| 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 |
175000; 246000; 198000; NA; 208000; 210000 | — |
| SECONDARY PK: Area Under the Concentration Curve (AUC) of LY3023414 in Part D |
1005; 1751; 3809; 1303; 1293; NA | — |
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 screen
Data sourced from ClinicalTrials.gov (NCT02079636). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.