Study of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Patients With Metastatic Breast Cancer (MK-7962-012)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the percentage of participants in each sotatercept dose regimen who achieve a hematopoietic response during the treatment period including up to 2 months after the last dose of sotatercept treatment of chemotherapy-induced anemia (CIA) in participants with metastatic breast cancer. Hematopoietic response was defined as an increase in hemoglobin concentration of ≥ 1 g/dL relative to baseline for 28 consecutive days during the treatment period including up to 2 months after the last dose of sotatercept in the absence of red blood cell (RBC) transfusion or treatment with an erythropoiesis-stimulating agent (ESA).

Official Title
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A Phase 2, Double-blind, Randomized, Placebo-Controlled Study of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Metastatic Breast Cancer

Conditions
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Chemotherapy Induced Anemia

Intervention / Treatment
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* Biological: Sotatercept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a histologically confirmed diagnosis of breast cancer documented by cytology or biopsy. Has evidence of metastatic breast cancer with a minimum of one lesion per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v 1.1) criteria. Is receiving a chemotherapy regimen including one of the following: anthracycline, taxane, gemcitabine, vinorelbine or capecitabine. Has planned treatment with the same chemotherapy regimen for a minimum of 9 weeks after Day 1 of study intervention administration. ≥ 30 days elapsed (from Day 1) since previous treatment with an erythropoiesis stimulating agent (ESA) (including treatment with intravenous (IV) iron) for chemotherapy induced anemia. ≥ 7 days elapsed (from Day 1) since the last red blood cell (RBC) transfusion and receipt of ≤ 2 units of blood in the past 30 days. Life expectancy of ≥ 6 months. Exclusion Criteria: Has had prior radiation therapy to > 20% of the whole skeleton. Has had > 5 prior chemotherapy treatment regimens for metastatic breast cancer. Has a history of autoimmune or hereditary hemolysis or gastrointestinal bleeding. Has clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic or genitourinary disease unrelated to underlying hematologic disorder. Has heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher. Has a recent history of thrombosis, deep vein thrombosis (DVT), pulmonary emboli, or embolic stroke, occurring within the last 6 months. Has untreated central nervous system (CNS) metastases or CNS metastases treated with whole brain radiotherapy < 6 months prior to Day 1. Has a diagnosis of a myeloid malignancy or known history of myelodysplasia. Has a history of second malignancy within 5 years (except excised and cured basal cell carcinoma, squamous cell carcinoma of the skin or cervical carcinoma in situ). Has had administration of IV antibiotics or febrile (temperature elevation > 38 ° C) within 14 days of Day 1. Has uncontrolled hypertension. Has known history of hepatitis B surface antigen (HBsAg and HB core antibody (Ab)), human immunodeficiency virus (HIV) antibody or active hepatitis C. Has clinically significant iron (transferrin saturation < 20%), vitamin B12, or folate deficiency. Has a history of anemia as a result of inherited hemoglobinopathy such as sickle cell anemia or thalassemia. Has a history of autoimmune or hereditary hemolysis; active gastrointestinal bleeding (within the last 6 months as compared to Day 1). Has received treatment with another investigational drug or device within 1 month prior to Day 1. Is pregnant or lactating. Has a history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product. Has had major surgery within 30 days prior to Day 1 (patients must have completely recovered from any previous surgery prior to Day 1).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotatercept 0.1 mg/kg<br>Participants will receive sotatercept 0.1 mg/kg subcutaneously every 28 days up to 4 doses. | Biological: Sotatercept<br>* up to 4 subcutaneous doses of sotatercept given once every 28 days<br>* Other names: ACE-011;|
| Experimental: Sotatercept 0.3 mg/kg<br>Participants will receive sotatercept 0.3 mg/kg subcutaneously every 28 days up to 4 doses. | Biological: Sotatercept<br>* up to 4 subcutaneous doses of sotatercept given once every 28 days<br>* Other names: ACE-011;|
| Experimental: Sotatercept 0.5 mg/kg<br>Participants will receive sotatercept 0.5 mg/kg subcutaneously every 28 days up to 4 doses. | Biological: Sotatercept<br>* up to 4 subcutaneous doses of sotatercept given once every 28 days<br>* Other names: ACE-011;|
| Placebo Comparator: Placebo<br>Participants will receive placebo subcutaneously every 28 days up to 4 doses. | Drug: Placebo<br>* up to 4 subcutaneous doses of placebo given once every 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Hematopoietic Response | Hematopoietic response rate is defined as the percentage of participants who had increase in hemoglobin concentration of ≥ 1 g/dL relative to baseline for 28 consecutive days during the treatment period including up to 2 months after the last dose of study treatment in the absence of red blood cell (RBC) transfusion or treatment with an erythropoiesis-stimulating agent (ESA). The percentage of participants who achieved hematopoietic response is presented. | Baseline and Up to  145 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced an Adverse Event (AE) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced AEs is reported. | Up to  175 Days | 
| Number of Participants Who Discontinued Study Intervention Due to an Adverse Event | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study intervention due to AEs is reported. | Up to  85 Days | 
| Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥ 2 g/dL | Percentage of participants achieving an increase from baseline hemoglobin of ≥ 2 g/dL for 28 consecutive days during the treatment period and up to 2 months after the last dose of study treatment in the absence of RBC transfusion or treatment with an ESA. The percentage of participants achieving an increase from baseline hemoglobin of ≥ 2 g/dL for 28 consecutive days is presented. | Baseline and Up to  145 Days | 
| Percentage of Participants Achieving an Increase From Baseline Hemoglobin ≥ 11 g/dL | Percentage of participants achieving hemoglobin ≥ 11 g/dL for 28 consecutive days during the treatment period and up to 2 months after the last dose of study treatment in the absence of RBC transfusion or treatment with an ESA. The percentage of participants achieving an increase from baseline hemoglobin of ≥ 11 g/dL for 28 consecutive days is presented. | Baseline and Up to  145 Days | 
| Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥2 g/dL and/or Hemoglobin ≥ 11 g/dL | Percentage of participants achieving an increase from baseline hemoglobin of ≥ 2 g/dL and/or hemoglobin ≥ 11 g/dL for 28 consecutive days during the treatment period and up to 2 months after the last dose of study treatment in the absence of RBC transfusion or treatment with an ESA. The percentage of participants achieving an increase from baseline hemoglobin of ≥ 2 g/dL and/or hemoglobin ≥ 11 g/dL for 28 consecutive days is presented. | Baseline and Up to  145 Days | 
| Duration of Hematopoietic Response for Hemoglobin ≥ 1 g/dL | Duration of hematopoietic response is defined as the time period from the first time hemoglobin increases at least ≥ 1 g/dL from baseline to the last time there is hemoglobin ≥ 1 g/dL increase from baseline. Duration of response is only calculated for a responder and will be at least 28 days. The duration of response is only calculated for a patient who meets the primary efficacy endpoint. The data for duration of response for ≥ 1 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Duration of Hematopoietic Response for Hemoglobin ≥ 2 g/dL | Duration of hematopoietic response is defined as the time period from the first time hemoglobin increases at least ≥ 2 g/dL from baseline to the last time there is hemoglobin ≥ 2 g/dL increase from baseline. Duration of response is only calculated for a responder and will be at least 28 days. The duration of response is only calculated for a patient who meets the primary efficacy endpoint. The data for duration of response for hemoglobin ≥ 2 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Duration of Hematopoietic Response for Hemoglobin ≥ 11 g/dL | Duration of hematopoietic response is defined as the time period from the first time hemoglobin increases at least ≥ 11 g/dL from baseline to the last time there is hemoglobin ≥ 11 g/dL increase from baseline. Duration of response is only calculated for a responder and will be at least 28 days. The duration of response is only calculated for a patient who meets the primary efficacy endpoint. The data for duration of response for hemoglobin ≥ 11 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Duration of Hematopoietic Response for Hemoglobin Increases ≥ 1 g/dL and/or Hemoglobin Concentration ≥ 11 g/dL | Duration of hematopoietic response is defined as the time period the first time hemoglobin increases ≥ 1 g/dL and/or hemoglobin concentration is ≥ 11 g/dL from baseline to the last time when the same response is maintained. The data for duration of response for hemoglobin ≥ 1 g/dL and/or hemoglobin concentration ≥ 11 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Duration of Hematopoietic Response for Hemoglobin Increases ≥ 2 g/dL, and/or Hemoglobin Concentration ≥ 11 g/dL | Duration of hematopoietic response is defined as the time period the first time hemoglobin increases ≥ 2 g/dL, and/or hemoglobin concentration is ≥ 11 g/dL from baseline to the last time when the same response is maintained. The data for duration of response for hemoglobin ≥ 2 g/dL and/or hemoglobin concentration ≥ 11 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Time to Achieve Hematopoietic Response of Hemoglobin ≥ 1 g/dL Increase From Baseline | Time to achieve hematopoietic response based on ≥ 1 g/dL increase from baseline, is defined as the time from first dose of study treatment to the first hemoglobin increase ≥ 1 g/dL that was maintained for at least 28 consecutive days. The data for time to achieve hematopoietic response for hemoglobin ≥ 1 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Time to Achieve Hematopoietic Response of Hemoglobin ≥ 2 g/dL Increase From Baseline | Time to achieve hematopoietic response based on ≥ 2 g/dL increase from baseline, is defined as the time from first dose of study treatment to the first hemoglobin increase ≥ 2 g/dL that was maintained for at least 28 consecutive days. The data for duration of response for hemoglobin ≥ 2 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Time to Achieve Hematopoietic Response of Hemoglobin ≥ 11 g/dL From Baseline | Time to achieve hematopoietic response based on hemoglobin ≥ 11 g/dL, defined as the time from first dose of study treatment to the first hemoglobin ≥ 11 g/dL that was maintained for at least 28 consecutive days. The data for duration of response for hemoglobin ≥ 11 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Time to Achieve Hematopoietic Response of First Hemoglobin Increase ≥ 1 g/dL and/or Hemoglobin ≥ 11 g/dL | Time to achieve hematopoietic response based on multiple criteria categories, defined as the time from first dose of study treatment to first hemoglobin increase ≥ 1 g/dL and/or hemoglobin ≥ 11 g/dL that was maintained for at least 28 consecutive days. The data for duration of response for hemoglobin increase from baseline ≥ 1 g/dL and/or ≥ 11 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Time to Achieve Hematopoietic Response of First Hemoglobin Increase ≥ 2 g/dL and/or Hemoglobin ≥ 11 g/dL | Time to achieve hematopoietic response, defined as the time from first dose of study treatment to first hemoglobin increase ≥ 2 g/dL and/or hemoglobin ≥ 11 g/dL that was maintained for at least 28 consecutive days. The data for duration of response for hemoglobin increase from baseline ≥ 2 g/dL and/or ≥ 11 g/dL from baseline is presented. | Baseline and Up to  145 Days | 
| Percentage of Participants Who Received RBC Transfusion or Treatment With an ESA | The percentage of participants who received RBC transfusion or treatment with an ESA in each study treatment group as well as within each cycle of each study treatment is presented. | Up to Day 141 | 
| Objective Response Rate (ORR) for Target Lesions at Day 64 Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1). | ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of participants who experienced a CR or PR at Day 64 is presented. | Baseline and Day 64 | 
| Objective Tumor Response Rate for Non-target Lesions at Day 64 Using RECIST v 1.1. | ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of participants who experienced a CR or PR of non-target lesions at Day 64 is presented. | Day 64 | 
| Objective Tumor Response Rate for Target Lesions on Day 113 Using RECIST v 1.1. | ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of participants who experienced a CR or PR at Day 113 is presented. | Day 113 | 
| Objective Tumor Response Rate for Non-target Lesions on Day 113 Using RECIST v 1.1. | ORR is defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of participants who experienced a CR or PR of non-target lesions at Day 113 is presented. | Day 113 | 
| Progression-free Survival (PFS) | PFS was defined as the time from start of the chemotherapy regimen (which could have occurred prior to study start and collected as prior anticancer therapy) to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 is presented. | From start of chemotherapy (which could have occurred prior to study start) up to Study Day 281 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, metastatic, breast, cancer