Anemia
Conditions
Keywords
Cancer Related Anemia
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.
Interventions
DRUGLY2787106
Administered IV.
DIETARY_SUPPLEMENTIron Supplementation
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Events | 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. |
| Mean Change From Baseline in Hemoglobin With or Without Oral Iron Supplementation | 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
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose for Future Studies: Maximum Tolerated Dose (MTD) | 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. |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) | 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. |
| Mean Change From Baseline in Reticulocyte Count | Baseline, Cycle 4 (7-day cycle) | Mean change in reticulocyte count from baseline to the end of Cycle 4. |
| Change From Baseline in Serum Iron | Baseline, Cycle 4 (7-day cycle) | Mean change in serum iron from baseline to the end of Cycle 4. |
| PK: Area Under the Curve (AUC[0-∞]) | 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. |
Countries
United States
Participant flow
Pre-assignment details
Part B participants who received 8 weekly doses and discontinued treatment were considered completers.
Participants by arm
| Arm | Count |
|---|---|
| Part A 0.3 mg/kg LY2787106 Part A: Participants received 0.3 mg/kg, LY2787106, IV, day 1 of up to three 21-day cycles. | 4 |
| Part A 1.0 mg/kg LY2787106 Part A: Participants received 1.0 mg/kg, LY2787106, IV, day 1 of up to three 21-day cycles. | 3 |
| Part A 3.0 mg/kg LY2787106 Part A: Participants received 3.0 mg/kg, LY2787106, IV, day 1 of up to three 21-day cycles. | 7 |
| Part A 10.0 mg/kg LY2787106 Part A: Participants received 10.0 mg/kg, LY2787106, IV, day 1 of up to three 21-day cycles. | 5 |
| Part B 10.0 mg/kg LY2787106 Part B: Participants received 10.0 mg/kg, LY2787106, IV, on day 1 of up to eight 7-day cycles. | 7 |
| Part B 10.0 mg/kg LY2787106+Iron Part B: Participants received 10.0 mg/kg, LY2787106, IV, on day 1 of up to eight 7-day cycles with daily oral iron supplementation. | 7 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Dose Limiting Toxicity Stopping Rule | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other anemia treatment | 1 | 0 | 2 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A 0.3 mg/kg LY2787106 | Total | Part B 10.0 mg/kg LY2787106+Iron | Part B 10.0 mg/kg LY2787106 | Part A 10.0 mg/kg LY2787106 | Part A 3.0 mg/kg LY2787106 | Part A 1.0 mg/kg LY2787106 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 7.3 | 64.9 years STANDARD_DEVIATION 10 | 62.7 years STANDARD_DEVIATION 7.5 | 66.3 years STANDARD_DEVIATION 9.2 | 63.2 years STANDARD_DEVIATION 7.9 | 62.1 years STANDARD_DEVIATION 13.4 | 76.7 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 32 Participants | 7 Participants | 6 Participants | 5 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 25 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 3 Participants |
| Region of Enrollment United States | 4 participants | 33 participants | 7 participants | 7 participants | 5 participants | 7 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 20 Participants | 6 Participants | 4 Participants | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 13 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 6 / 7 | 5 / 5 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 1 / 4 | 2 / 3 | 2 / 7 | 0 / 5 | 0 / 7 | 1 / 7 |
Outcome results
Primary
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.
Time frame: Baseline, Cycle 4 (7-day cycle)
Population: Evaluable population in Part B is defined as a participant who received all 4 of the first 4 per-cycle doses of study medication, maintained at least 60% compliance with oral iron therapy during the first 4 cycles of LY2787106 (if enrolled to the oral iron cohort), and who had a hemoglobin assessment after each of the first 4 doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 0.3 mg/kg LY2787106 | Mean Change From Baseline in Hemoglobin With or Without Oral Iron Supplementation | -0.5 grams per deciliter (g/dL) | Standard Deviation 0.49 |
| Part A 1.0 mg/kg LY2787106 | Mean Change From Baseline in Hemoglobin With or Without Oral Iron Supplementation | -0.2 grams per deciliter (g/dL) | Standard Deviation 0.8 |
Primary
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.
Time frame: Baseline to Study Completion (up to 5 Years)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A 0.3 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 TEAE event | 4 participants |
| Part A 0.3 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 SAE event | 1 participants |
| Part A 1.0 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 TEAE event | 3 participants |
| Part A 1.0 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 SAE event | 2 participants |
| Part A 3.0 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 TEAE event | 6 participants |
| Part A 3.0 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 SAE event | 2 participants |
| Part A 10.0 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 TEAE event | 5 participants |
| Part A 10.0 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 SAE event | 0 participants |
| Part B 10 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 TEAE event | 0 participants |
| Part B 10 mg/kg LY2787106 | Number of Participants With Clinically Significant Events | Participants with at least 1 SAE event | 0 participants |
| Part B 10 mg/kg LY2787106+Iron | Number of Participants With Clinically Significant Events | Participants with at least 1 TEAE event | 0 participants |
| Part B 10 mg/kg LY2787106+Iron | Number of Participants With Clinically Significant Events | Participants with at least 1 SAE event | 1 participants |
Secondary
Change From Baseline in Serum Iron
Mean change in serum iron from baseline to the end of Cycle 4.
Time frame: Baseline, Cycle 4 (7-day cycle)
Population: Evaluable Population in Part B is defined as a participant who has received all 4 of the first 4 per-cycle doses of study dose, maintained at least 60% compliance with oral iron therapy during the first 4 cycles of LY2787106 (if enrolled to the oral iron cohort), and who has had a hemoglobin assessment after each of the first 4 doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 0.3 mg/kg LY2787106 | Change From Baseline in Serum Iron | -0.4 micromole per liter (umol/L) | Standard Deviation 6.17 |
| Part A 1.0 mg/kg LY2787106 | Change From Baseline in Serum Iron | -4.6 micromole per liter (umol/L) | Standard Deviation 9.2 |
Secondary
Mean Change From Baseline in Reticulocyte Count
Mean change in reticulocyte count from baseline to the end of Cycle 4.
Time frame: Baseline, Cycle 4 (7-day cycle)
Population: Evaluable Population in Part B is defined as a participant who has received all 4 of the first 4 per-cycle doses of study dose, maintained at least 60% compliance with oral iron therapy during the first 4 cycles of LY2787106 (if enrolled to the oral iron cohort), and who has had a hemoglobin assessment after each of the first 4 doses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 0.3 mg/kg LY2787106 | Mean Change From Baseline in Reticulocyte Count | 1.2 percentage of reticulytes | Standard Deviation 0.68 |
| Part A 1.0 mg/kg LY2787106 | Mean Change From Baseline in Reticulocyte Count | 0.0 percentage of reticulytes | Standard Deviation 0.46 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax)
Cmax is the maximum serum concentration after a single IV dose of the study drug.
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
Population: All participants who received at least 1 dose of study drug and who had evaluable PK data for Cmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 0.3 mg/kg LY2787106 | Pharmacokinetics (PK): Maximum Concentration (Cmax) | 5450 nanogram per milliliter (ng/ml) | Standard Deviation 24 |
| Part A 1.0 mg/kg LY2787106 | Pharmacokinetics (PK): Maximum Concentration (Cmax) | 22300 nanogram per milliliter (ng/ml) | Standard Deviation 27 |
| Part A 3.0 mg/kg LY2787106 | Pharmacokinetics (PK): Maximum Concentration (Cmax) | 79000 nanogram per milliliter (ng/ml) | Standard Deviation 15 |
| Part A 10.0 mg/kg LY2787106 | Pharmacokinetics (PK): Maximum Concentration (Cmax) | 205000 nanogram per milliliter (ng/ml) | Standard Deviation 12 |
| Part B 10 mg/kg LY2787106 | Pharmacokinetics (PK): Maximum Concentration (Cmax) | 258000 nanogram per milliliter (ng/ml) | Standard Deviation 15 |
| Part B 10 mg/kg LY2787106+Iron | Pharmacokinetics (PK): Maximum Concentration (Cmax) | 199000 nanogram per milliliter (ng/ml) | Standard Deviation 12 |
Secondary
PK: Area Under the Curve (AUC[0-∞])
AUC is the area under the concentration versus time curve from time zero to infinity.
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
Population: All participants who received at least 1 dose of study drug and who had evaluable PK data for AUC\[0-∞\]).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A 0.3 mg/kg LY2787106 | PK: Area Under the Curve (AUC[0-∞]) | 663 micrograms∙hour per milliliter (µg∙h/mL) | Standard Deviation 42 |
| Part A 1.0 mg/kg LY2787106 | PK: Area Under the Curve (AUC[0-∞]) | 2146 micrograms∙hour per milliliter (µg∙h/mL) | Standard Deviation 64 |
| Part A 3.0 mg/kg LY2787106 | PK: Area Under the Curve (AUC[0-∞]) | 8934 micrograms∙hour per milliliter (µg∙h/mL) | Standard Deviation 39 |
| Part A 10.0 mg/kg LY2787106 | PK: Area Under the Curve (AUC[0-∞]) | 24503 micrograms∙hour per milliliter (µg∙h/mL) | Standard Deviation 19 |
| Part B 10 mg/kg LY2787106 | PK: Area Under the Curve (AUC[0-∞]) | 21000 micrograms∙hour per milliliter (µg∙h/mL) | Standard Deviation 19 |
| Part B 10 mg/kg LY2787106+Iron | PK: Area Under the Curve (AUC[0-∞]) | 16798 micrograms∙hour per milliliter (µg∙h/mL) | Standard Deviation 27 |
Secondary
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: 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.
Time frame: Baseline to Cycle 1 of Part A
Population: MTD was not determined in this study, so zero participants were analyzed.