A Study of LY2835219 in Japanese Participants With Advanced Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate safety and side effects of LY2835219 in Japanese participants with advanced cancer.

Official Title
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A Phase 1 Study of LY2835219 in Japanese Patients With Advanced Cancer

Conditions
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Neoplasm Metastasis, Lymphoma

Intervention / Treatment
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* Drug: LY2835219


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histological or cytological evidence of a diagnosis of cancer (either a solid tumor or a lymphoma) that is advanced and/or metastatic Must be, in the judgment of the investigator, an appropriate candidate for the experimental therapy after available standard therapies have failed to provide clinical benefit for their disease Have the presence of measurable or non-measurable disease as defined by the Response Evaluation Criteria in Solid Tumors Guideline Version 1.1, or the Revised Response Criteria for Malignant Lymphoma Guideline Have adequate organ function Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, and investigational therapy, for at least 21 days before the first dose of study drug and recovered from the acute effects of any such therapy Males must agree to use medically approved barrier contraceptive precautions during the study and for 3 months following the last dose of study drug Females with child bearing potential: must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug, must have had a negative serum or urine pregnancy test ≤7 days before the first dose of study drug. A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding enters the study, the female must stop breastfeeding from the day of the first study drug administration until at least 3 months after the last administration Have an estimated life expectancy of ≥12 weeks Are able to swallow capsules Exclusion Criteria: Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication Have a medical history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (e.g., ventricular tachycardia and ventricular fibrillation) or sudden cardiac arrest Have a baseline with any of the following findings on screening electrocardiogram (ECG): ventricular tachycardia, ventricular fibrillation, abnormal QTc using Bazett's formula (QTcB) (defined as ≥470 milliseconds), or evidence of acute myocardial ischemia Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel) Have symptomatic central nervous system (CNS) malignancy or metastasis. For asymptomatic participants without history of CNS malignancy or metastases Have evidence or history of a leukemia Have received a stem-cell transplant. As an exception, a participant with lymphoma who received an autologous stem-cell transplant is eligible for the study, if more than 75 days have passed before the initial dose of study drug Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV], hepatitis B, or hepatitis C)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - 100 mg Abemaciclib<br>100 milligram (mg) abemaciclib administered orally every 12 hours (Q12H) in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met. | Drug: LY2835219<br>* Administered orally<br>* Other names: abemaciclib;|
| Experimental: Cohort 2 - 150 mg Abemaciclib<br>150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met. | Drug: LY2835219<br>* Administered orally<br>* Other names: abemaciclib;|
| Experimental: Cohort 3 - 200 mg Abemaciclib<br>200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met. | Drug: LY2835219<br>* Administered orally<br>* Other names: abemaciclib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT) | DLT is defined as an adverse event between Day -3 and Day 29 of Cycle 1 that is possibly related to the study drug and fulfills any one of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. | Cycle 1 = 32 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Maximum plasma concentration on Day -3 and Day 28 of Cycle 1. | Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hours (hr) postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days) | 
| Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUC on Day -3 and Day 28 of Cycle 1 are AUC from time zero to infinity [AUC(0-∞)] and AUC during one dosing interval at steady state (AUCτ,ss), respectively. | Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hr postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days) | 
| Percentage of Participants With a Tumor Response: Objective Response Rate (ORR) | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. | Baseline to Measured Progressive Disease (Up To 24 months) |