A Phase 1 Study of LY2787106 in Cancer and Anemia

• ClinicalTrials.gov Identifier: NCT01340976
• Recruitment Status: Completed
• First Posted: April 25, 2011
• Results First Posted: October 3, 2018
• Last Update Posted: October 3, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anemia	Drug: LY2787106; Dietary Supplement: Iron Supplementation	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase 1 Safety Study of LY2787106 in Patients With Cancer and Anemia
• Study Start Date: January 2010
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: LY2787106 Dose Escalation; 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; Administered IV.
Experimental: 10 mg/kg LY2787106; 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; Administered IV.
Experimental: 10 mg/kg LY2787106+Iron; 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; Administered IV.; Dietary Supplement: Iron Supplementation; Administered orally.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Clinically Significant Events [ Time Frame: Baseline to Study Completion (up to 5 Years) ]
   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.
2. Mean Change From Baseline in Hemoglobin With or Without Oral Iron Supplementation [ Time Frame: Baseline, Cycle 4 (7-day cycle) ]
   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.

Secondary Outcome Measures :

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) [ Time Frame: 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 ]
   Cmax is the maximum serum concentration after a single IV dose of the study drug.
2. PK: Area Under the Curve (AUC[0-∞]) [ Time Frame: 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 ]
   AUC is the area under the concentration versus time curve from time zero to infinity.
3. Recommended Dose for Future Studies: Maximum Tolerated Dose (MTD) [ Time Frame: Baseline to Cycle 1 of Part A ]

   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:

   1. 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.
   2. ≥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.
   3. ≥ Grade 3 cytokine release syndrome/acute infusion reaction.
   4. Other ≥ Grade 3 hematological or non-hematological toxicity.
4. Change From Baseline in Serum Iron [ Time Frame: Baseline, Cycle 4 (7-day cycle) ]
   Mean change in serum iron from baseline to the end of Cycle 4.
5. Mean Change From Baseline in Reticulocyte Count [ Time Frame: Baseline, Cycle 4 (7-day cycle) ]
   Mean change in reticulocyte count from baseline to the end of Cycle 4.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, California

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

La Jolla, California, United States, 92093

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Santa Monica, California, United States, 90404

United States, Indiana

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Indianapolis, Indiana, United States, 46202

United States, Pennsylvania

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Philadelphia, Pennsylvania, United States, 19106

United States, Texas

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Dallas, Texas, United States, 75246

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Houston, Texas, United States, 77030

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

The Woodlands, Texas, United States, 77380

United States, Washington

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Seattle, Washington, United States, 98109

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Vancouver, Washington, United States, 98684

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vadhan-Raj S, Abonour R, Goldman JW, Smith DA, Slapak CA, Ilaria RL Jr, Tiu RV, Wang X, Callies S, Cox J, Tuttle JL, Lau YK, Roeland EJ. A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia. J Hematol Oncol. 2017 Mar 21;10(1):73. doi: 10.1186/s13045-017-0427-x.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01340976
• Other Study ID Numbers: 13131; I3S-MC-JABA ( Other Identifier: Eli Lilly and Company )
• First Posted: April 25, 2011
• Results First Posted: October 3, 2018
• Last Update Posted: October 3, 2018
• Last Verified: February 2018

Keywords provided by Eli Lilly and Company:

Cancer Related Anemia

Additional relevant MeSH terms:

Anemia; Hematologic Diseases