A Phase 1 Study of LY2787106 in Cancer and Anemia

Study Overview
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Brief Summary
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This study will evaluate the safety LY2787106 in participants with cancer and anemia. It will also evaluate when LY2787106 can improve anemia. This study has two parts: Part A is a dose escalation evaluation. Part B is an evaluation of LY2787106 at a defined dose given with and without iron supplementation.

Official Title
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A Phase 1 Safety Study of LY2787106 in Patients With Cancer and Anemia

Conditions
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Anemia

Intervention / Treatment
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* Drug: LY2787106
* Dietary Supplement: Iron Supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histological or cytological evidence of non-myeloid cancer (solid tumors, lymphomas or multiple myeloma) that is metastatic and/or incurable Have been treated with at least one systemic (oral, intravenous, or subcutaneous) anti-cancer therapy or regimen Have a hemoglobin of less than or equal to 11 grams/deciliter (g/dL) Have a hepcidin level of greater than or equal to 5 nanograms/milliliter (ng/mL) Have given written informed consent prior to any study-specific procedures Have adequate hematologic, hepatic, and renal organ function Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 Available for the duration of the study and willing to follow study procedures If male or female with reproductive potential: Must agree to use medically approved contraception during the trial and for 4 months following the last dose of study drug If female with child bearing potential: Have a negative serum pregnancy test Have an estimated life expectancy of greater than or equal to 12 weeks Exclusion Criteria: Have received treatment in the previous 21 days with, or have not recovered fully from, a drug that has not received regulatory approval for any indication Have received erythropoiesis-stimulating agents in the previous 21 days or red blood cell transfusions in the previous 14 days, or in the investigator's opinion, likely to need red blood cell transfusion more frequently than every 21 days Have received parenteral iron supplementation within the prior 14 days Have a documented history of pure red cell aplasia, thalassemia major or sickle cell disease Have a history of cirrhosis or major organ transplantation QTc greater than 470 millisecond (msec) Have evidence of clinically significant hemolysis or bleeding Have a clinically significant systemic infection within 14 days of enrollment Have a suspected or confirmed history of hemochromatosis. Have other serious preexisting medical conditions (left to the discretion of the investigator) Have symptomatic central nervous system malignancy or metastasis (screening not required) Have acute or chronic leukemia Are a female who is pregnant or lactating Have a history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C (screening not required) Have received external beam radiotherapy to more than 25% of the bone marrow Have known clinically significant hypersensitivity to biologic agents Have received live vaccine(s) within 1 month of screening or with plans of doing that during the participation to the study Have a history of congestive heart failure with New York Heart Association (NYHA) Class greater than 2 (NYHA Class 1 and 2 are eligible), unstable angina or recent myocardial infarction (within 1 year prior to administration of study drug)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2787106 Dose Escalation<br>Part A: Dose escalation starting at 0.3 milligram/kilogram (mg/kg), intravenously (IV), day one of up to three 21-day cycles. | Drug: LY2787106<br>* Administered IV.<br>|
| Experimental: 10 mg/kg LY2787106<br>Part B: 10 mg/kg of LY2787106, administered IV, on day one of up to eight 7-day cycles. Participants who do not experience a stopping rule and who are felt to be benefiting during the defined treatment period may receive additional doses at the discretion of the investigator. | Drug: LY2787106<br>* Administered IV.<br>|
| Experimental: 10 mg/kg LY2787106+Iron<br>Part B: 10 mg/kg of LY2787106, administered IV, on day one of up to eight 7-day cycles with daily oral iron supplementation. Participants who do not experience a stopping rule and who are felt to be benefiting during the defined treatment period may receive additional doses at the discretion of the investigator. | Drug: LY2787106<br>* Administered IV.<br>Dietary Supplement: Iron Supplementation<br>* Administered orally.<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 Events | Number of participants with one or more treatment emergent adverse event (TEAE) or any Serious AE (SAE). A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. | Baseline to Study Completion (up to 5 Years) | 
| Mean Change From Baseline in Hemoglobin With or Without Oral Iron Supplementation | This analysis assesses the mean change in Hemoglobin from baseline to the end of Cycle 4. The analysis was carried separately for Cohort B1 without supplemental iron and Cohort B2 with supplemental iron. | Baseline, Cycle 4 (7-day cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) | Cmax is the maximum serum concentration after a single IV dose of the study drug. | Days 1, 2, and 4 of Cycles 1 and 5, Day 1 of Cycles 2, 3, 4, 6, 7 and 8 (Part A 21-day cycles, Part B 7-day cycles) and 1, 3, and 9 weeks after the last infusion | 
| PK: Area Under the Curve (AUC[0-∞]) | AUC is the area under the concentration versus time curve from time zero to infinity. | Days 1, 2, and 4 of Cycles 1 and 5, Day 1 of Cycles 2, 3, 4, 6, 7 and 8 (Part A 21-day cycles, Part B 7-day cycles) and 1, 3, and 9 weeks after the last infusion | 
| Recommended Dose for Future Studies: Maximum Tolerated Dose (MTD) | MTD is defined as being the highest tested dose below the level at which one-third or more of participants experience a Dose-limiting toxicity (DLT). DLT is defined as an adverse event occurring in any part of the study that is related to the study medication, occurs during Cycle 1 of Part A, and fulfills any one of the following criteria: Clinically significant Grade 2 toxicity, such as angina, arrhythmia, seizure, dyspnea, rash with significant blistering or desquamation, or other event deemed significant by either the investigator. ≥Grade 3 anemia (excluding participants with baseline <9.0 g/dL) or hemoglobin (Hb) decrease >1.0 g/dL if baseline Hb <9.0 g/dL, confirmed by 2 independent measurements. ≥ Grade 3 cytokine release syndrome/acute infusion reaction. Other ≥ Grade 3 hematological or non-hematological toxicity. | Baseline to Cycle 1 of Part A | 
| Change From Baseline in Serum Iron | Mean change in serum iron from baseline to the end of Cycle 4. | Baseline, Cycle 4 (7-day cycle) | 
| Mean Change From Baseline in Reticulocyte Count | Mean change in reticulocyte count from baseline to the end of Cycle 4. | Baseline, Cycle 4 (7-day cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer Related Anemia