A Phase 1 Study of LY2835219 In Participants With Advanced Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine a safe dose of LY2835219 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2835219 in this population. Efficacy measures will be used to assess the activity of LY2835219 in this population.

Official Title
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A Phase 1 Study of a CDK 4/6 Dual Inhibitor in Participants With Advanced Cancer

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: LY2835219
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all Parts (Dose escalation and expansion): The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy either after available standard therapies have ceased to provide clinical benefit (Parts A, B, C, D, E and F) or in combination with fulvestrant (Part G only) For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic For Dose Expansion (Parts B, C, D, E, F and G): The participant must have histological or cytological evidence of one of the following cancers: Part B: Non-small cell lung cancer of any subtype that is advanced and/or metastatic Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy Part D: Breast cancer that is advanced and/or metastatic Part E: Melanoma that is advanced and/or metastatic Part F: Colorectal Cancer Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma For Parts A and G: Have measurable or nonmeasurable disease For Parts B, C, D, E and F: Have measurable disease Have given written informed consent prior to any study-specific procedures Have adequate hematologic, hepatic, and renal function Have a performance status less than or equal to 1 for Dose Escalation (Part A) and less than or equal to 2 for Dose Confirmation (Parts B, C, D, E, F and G) on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) with the exception of fulvestrant (for Part G only) 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 Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug Females with child bearing potential must have a negative serum pregnancy test within 3 days of the first dose of study drug Have an estimated life expectancy of greater than or equal to 12 weeks Are able to swallow capsules Exclusion Criteria: Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively 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), sudden cardiac death or sudden cardiac arrest 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) For Dose Escalation (Part A): Have central nervous system (CNS) malignancy or metastasis For Dose Confirmation (Parts B, D, E, F and G): Have CNS metastasis that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids For Dose Confirmation (Part C): Have glioblastoma multiforme that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids Have an acute leukemia Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug Females who are pregnant or lactating 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

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2835219<br> | Drug: LY2835219<br>* Administered orally, daily for 28-day cycles for two planned cycles. For Part G only in addition to LY2835219 as above, fulvestrant is administered as specified in the label. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria is met.<br>* Other names: abemaciclib;Drug: Fulvestrant<br>* Fulvestrant is administered intramuscularly into the buttocks as specified in the label in Part G only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinically significant effects (physical assessments and safety lab tests) |  | Baseline through study completion (approximately 38 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with tumor response |  | Baseline through study completion (approximately 38 months) | 
| Pharmacokinetics, maximum plasma concentration (Cmax) |  | Days -3, -2, -1, Days 1, 15, 22, 28 and 29 of Cycle 1 | 
| Pharmacokinetics, area under the curve (AUC) |  | Days -3, -2, -1, Days 1, 15, 22, 28 and 29 of Cycle 1 | 
| Recommended dose for phase 2 studies |  | Baseline to study completion (approximately 38 months) |