A Study of LY3009120 in Participants With Advanced Cancer or Cancer That Has Spread to Other Parts of Their Body

Study Overview
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Brief Summary
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The main purpose of this study is to see how safe the investigational drug known as LY3009120 is and whether it will work to help people with advanced cancer or cancer that has spread to other parts of the body.

Official Title
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A Phase 1 Study of LY3009120 in Patients With Advanced or Metastatic Cancer

Conditions
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Neoplasms, Neoplasm Metastasis, Melanoma, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms

Intervention / Treatment
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* Drug: LY3009120 capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced or metastatic cancer Other available therapies have failed to cure the cancer The cancer that has no proven effective therapy The cancer can be biopsied (depending on the tumor type and/or the dose of drug received, tumor biopsies may be required) Able to swallow capsules Exclusion Criteria: Have active cancer in the brain or spinal cord Have an active infection of any kind (fungal, viral, or bacterial) Have a cancer of the blood Are pregnant or breastfeeding Have some types of eye problems or impairments

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Dose Escalation<br>LY3009120 50 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met. | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort 2 Dose Escalation<br>LY3009120 100 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met. | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort 3 Dose Escalation<br>LY3009120 200 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met. | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort 4 Dose Escalation<br>LY3009120 400 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort 5 Dose Escalation<br>LY3009120 500 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort 6 Dose Escalation<br>LY3009120 300 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort A Dose Confirmation<br>LY3009120 300 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met. | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort B Dose Confirmation<br>LY3009120 300 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met. | Drug: LY3009120 capsule<br>* Administered orally.<br>|
| Experimental: Cohort C Dose Confirmation<br>LY3009120 300 mg given orally twice daily every 12 hours for a 28-day cycle. Participants may continue to receive study drug until discontinuation criteria are met. | Drug: LY3009120 capsule<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of LY3009120 | Maximum tolerated dose for the recommended Phase 2 dose (RP2D) of LY3009120 that might be safely administered to participants with advanced and/or metastatic cancer. Dose-limiting toxicity (DLT) is defined as an adverse event (AE) during Cycle 1 (28 days) that was possibly related to the study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: ≥Grade 3 non-hematological toxicity except nausea/vomiting, diarrhea, or constipation that can be controlled with appropriate care; Grade 3 elevations of ALT and/or AST lasting fewer than 8 days (without evidence of other hepatic injury); Grade 3 rash that resolves or improves to a Grade 2 or less within 7 days; CTCAE Grade 4 hematological toxicity of >5 days duration; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia with bleeding; Grade 3 febrile neutropenia. | Cycle 1 (28 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Tumor Response | Number of participants with tumor response using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is defined as at least a 30% decrease in the sum of diameter of target lesions. SD which is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. | Baseline through progressive disease (Up to 7.36 months) | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3009120 Cycle 1 Day 1 | PK: Maximum concentration of LY3009120 after a single oral dose Cycle 1 Day 1. | Cycle 1 Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10 hours (h) post-dose | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) at Steady State of LY3009120 Cycle 1 Day 15 | PK: Maximum concentration of LY3009120 during a twice daily dosing interval at steady state, Cycle 1 Day 15. | Cycle 1 Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10 h post-dose | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3009120 Cycle 1 Day 28 | PK: Maximum concentration of LY3009120 during a twice daily dosing interval at steady state, Cycle 1 Day 28. | Cycle 1 Day 28: Predose, 0.5, 1, 2, 4, 6, 8, 10 h post-dose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3009120 Cycle 1 Day 1 | PK: area under the concentration versus time curve [0-∞] of LY3009120 after a single oral dose Cycle 1 Day1. | Cycle 1 Day 1: Predose, 0.5, 1, 2, 4, 6, 8, 10 h post-dose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the End of Dosing Interval at Steady State (AUC[0-τ]) of LY3009120 Cycle 1 Day 15 | PK: area under the concentration versus time curve from time 0 to the end of the twice daily dosing interval at steady state [AUC0-τ]. | Cycle 1 Day 15: Predose, 0.5, 1, 2, 4, 6, 8, 10 h post-dose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the End of Dosing Interval at Steady State (AUC[0-τ]) of LY3009120 Cycle 1 Day 28 | PK: area under the concentration versus time curve from time 0 to the end of the twice daily dosing interval at steady state AUC[0-τ]. | Cycle 1 Day 28: Predose, 0.5, 1, 2, 4, 6, 8, 10 h post-dose |