A Study of Prexasertib (LY2606368) in Combination With Ralimetinib in Participants With Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety of the study drug prexasertib in combination with ralimetinib in participants with advanced or metastatic cancer.

Official Title
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A Phase 1 Dose-Escalation Study of LY2606368 in Combination With Ralimetinib in Patients With Advanced or Metastatic Cancer

Conditions
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Advanced Cancer, Metastatic Cancer, Colorectal Cancer, Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: prexasertib
* Drug: ralimetinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced or metastatic cancer. Able to swallow tablets. For Part B, you will need to have colon cancer or non-small cell lung (NSCLC) cancer with KRAS and/or BRAF mutations. Discontinued all previous treatments for cancer and recovered from the acute effects from the therapy. Exclusion Criteria: Active infection (fungal, viral, or bacterial). Active cancer in your brain or spinal cord. Acute or chronic leukemia. Serious heart condition. Disease that requires immunosuppressant therapy. Diagnosis of inflammatory bowel disease. Major small bowel resection that interferes with your body's ability to absorb the oral medicine. Participated in other clinical trials investigating prexasertib or ralimetinib. Pregnant or breastfeeding. Other pre-existing conditions or medical history which your doctor will explain to you.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: prexasertib + ralimetinib<br>Cohort 1: 60 milligrams (mg) prexasertib (LY2606368) given intravenously (IV) and 100 mg ralimetinib given orally. Cohort 2: 60 mg prexasertib (LY2606368) given intravenously (IV) and 200 mg ralimetinib given orally. | Drug: prexasertib<br>* Administered IV<br>* Other names: LY2606368;Drug: ralimetinib<br>* Administered orally<br>* Other names: LY2228820;|
| Experimental: Part B1: prexasertib + ralimetinib (colorectal cancer)<br>60 mg prexasertib (LY2696368) given IV and 200 mg ralimetinib given orally. Participants receive prexasertib IV on Days 1 and 15 and ralimetinib every 12 hours (Q12H) Days 1 and 14 of a 28 day cycle. | Drug: prexasertib<br>* Administered IV<br>* Other names: LY2606368;Drug: ralimetinib<br>* Administered orally<br>* Other names: LY2228820;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Prexasertib and Ralimetinib |  | Cycle 1 (28 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Prexasertib |  | Cycle 1 Day 1 through Cycle 3 Day 1 (28 Day Cycles) | 
| PK: Area Under the Curve (AUC) of Prexasertib |  | Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| PK: Cmax of Ralimetinib |  | Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| PK: AUC of Ralimetinib |  | Cycle 1 Day 1 through Cycle 2 Day 1 (28 Day Cycles) | 
| Best Overall Response (BOR): Percentage of Participants with Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE) |  | Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Estimated up to 32 Weeks) | 
| Disease Control Rate (DCR): Percentage of Participants who Exhibit SD, CR or PR |  | Baseline through Measured Progressive Disease (Estimated up to 32 Weeks) | 
| Duration of Response (DOR) |  | Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 32 Weeks) | 
| Progression Free Survival (PFS) |  | Baseline to Objective Progression or Death Due to Any Cause (Estimated Up to 32 Weeks) |