Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Blood and Lymph Conditions

Breast Neoplasms

Anemia

Hematologic Diseases

Participants will receive sotatercept 0.1 mg/kg subcutaneously every 28 days up to 4 doses.

Participants will receive sotatercept 0.3 mg/kg subcutaneously every 28 days up to 4 doses.

Participants will receive sotatercept 0.5 mg/kg subcutaneously every 28 days up to 4 doses.

Participants will receive placebo subcutaneously every 28 days up to 4 doses.

up to 4 subcutaneous doses of sotatercept given once every 28 days

Sotatercept

up to 4 subcutaneous doses of placebo given once every 28 days

Placebo

Medical Director

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).

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

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

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Merck Sharp & Dohme LLC

The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all allocated participants.

Participants received sotatercept 0.1 mg/kg subcutaneously every 28 days up to 4 doses.

Sotatercept 0.1 mg/kg

Participants received sotatercept 0.3 mg/kg subcutaneously every 28 days up to 4 doses.

Sotatercept 0.3 mg/kg

Participants received sotatercept 0.5 mg/kg subcutaneously every 28 days up to 4 doses.

Sotatercept 0.5 mg/kg

Participants received placebo subcutaneously every 28 days up to 4 doses.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Participants weight in kilograms is presented as the mean for each treatment arm.

Weight

Weekly

Less Frequently

Chemotherapy frequency among the Modified Intent to Treat Group was differentiated as either weekly or less frequently for participants.

Chemotherapy Frequency

This is an acquired study. No restrictions were imposed on time on current chemotherapy prior to study entry, therefore PFS could have gone beyond the study duration. The time from start of current chemotherapy could have occurred prior to study start and collected as prior anticancer therapy, therefore the upper limit of the confidence interval in the "Sotatercept 0.5 mg/kg" arm, "1791.0 days", didn't exceed the timeframe of 281 days after study start.

Senior Vice President, Global Clinical Development

Overall

Received weekly chemotherapy and showed a response

Received less frequent chemotherapy and showed a response

Participants received sotatercept at one of the following doses: 0.1 mg/kg, 0.3 mg/kg, or 0.5 mg/kg subcutaneously every 28 days up to 4 doses.

All Sotatercept-treated Participants

All randomized participants who have confirmed CIA, received at least one dose of study intervention and on study intervention for at least 2 months (57 days).

Percentage of Participants Who Achieved a Hematopoietic Response

All participants who received at least one dose of study intervention.

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Study Intervention Due to an Adverse Event

All randomized participants who have confirmed CIA, received at least one dose of study intervention and on study treatment for at least 2 months (57 days).

Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥ 2 g/dL

Percentage of Participants Achieving an Increase From Baseline Hemoglobin ≥ 11 g/dL

Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥2 g/dL and/or Hemoglobin ≥ 11 g/dL

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a hematopoietic response of ≥1 g/dL and less than 2 g/dL increase from baseline.

Duration of Hematopoietic Response for Hemoglobin ≥ 1 g/dL

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a hematopoietic response of ≥2 g/dL and less than 11 g/dL increase from baseline.

Duration of Hematopoietic Response for Hemoglobin ≥ 2 g/dL

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days), and had a hematopoietic response of ≥11 g/dL increase from baseline.

Duration of Hematopoietic Response for Hemoglobin ≥ 11 g/dL

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days), and had a hematopoietic response of ≥ 1 g/dL and/or hemoglobin concentration is ≥11 g/dL increase from baseline.

Duration of Hematopoietic Response for Hemoglobin Increases ≥ 1 g/dL and/or Hemoglobin Concentration ≥ 11 g/dL

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a hematopoietic response of ≥ 2 g/dL and/or hemoglobin concentration is ≥11 g/dL increase from baseline.

Duration of Hematopoietic Response for Hemoglobin Increases ≥ 2 g/dL, and/or Hemoglobin Concentration ≥ 11 g/dL

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a hematopoietic response of ≥ 1 g/dL increase from baseline.

Time to Achieve Hematopoietic Response of Hemoglobin ≥ 1 g/dL Increase From Baseline

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a hematopoietic response of ≥ 2 g/dL increase from baseline.

Time to Achieve Hematopoietic Response of Hemoglobin ≥ 2 g/dL Increase From Baseline

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had hematopoietic response of ≥ 11 g/dL increase from baseline.

Time to Achieve Hematopoietic Response of Hemoglobin ≥ 11 g/dL From Baseline

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a hematopoietic response of ≥ 1 g/dL and/or hemoglobin concentration is ≥11 g/dL increase from baseline.

Time to Achieve Hematopoietic Response of First Hemoglobin Increase ≥ 1 g/dL and/or Hemoglobin ≥ 11 g/dL

Time to Achieve Hematopoietic Response of First Hemoglobin Increase ≥ 2 g/dL and/or Hemoglobin ≥ 11 g/dL

Overall RBC Transfusions

Overall ESAs

Overall Received RBC Transfusions or ESAs

Day 1 to Prior to Day 29 RBC Transfusions

Day 1 to Prior to Day 29 ESAs

Day 1 to Prior to Day 29 Received RBC Transfusions or ESAs

Day 29 to Prior to Day 57 RBC Transfusions

Day 29 to Prior to Day 57 ESAs

Day 29 to Prior to Day 57 Received RBC Transfusions or ESAs

Day 57 to Prior to Day 85 RBC Transfusions

Day 57 to Prior to Day 85 ESAs

Day 57 to Prior to Day 85 Received RBC Transfusions or ESAs

Day 85 to Prior to Day 141 RBC Transfusions

Day 85 to Prior to Day 141 ESAs

Day 85 to Prior to Day 141 Received RBC Transfusions or ESAs

Percentage of Participants Who Received RBC Transfusion or Treatment With an ESA

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not Evaluable

Not Applicable

All randomized participants who have confirmed CIA, received at least one dose of study intervention, on study intervention for at least 2 months (57 days) and had a response.

Objective Response Rate (ORR) for Target Lesions at Day 64 Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1).

Non-complete Response/Non-progressive disease

Objective Tumor Response Rate for Non-target Lesions at Day 64 Using RECIST v 1.1.

Objective Tumor Response Rate for Target Lesions on Day 113 Using RECIST v 1.1.

Objective Tumor Response Rate for Non-target Lesions on Day 113 Using RECIST v 1.1.

All randomized participants who received at least one dose of study intervention.

Progression-free Survival (PFS)

Overall Study

Participants will receive a single 35 mg dose of sotatercept by subcutaneous (SC) injection on Day 1, Day 43, and Day 85.

single 35 mg SC dose of sotatercept on study Day 1, Day 43, and Day 85

What hematopoietic precursor compartments as well as hemoglobin subtypes are affected by dosing with sotatercept (ACE-011)? Based upon a similar prior study with Procrit, Celgene has determined that all of these goals could be obtained by an intense 10-patient sotatercept (ACE-011) pharmacodynamic study, completed by two well-known experts in the red cell production field.

Study to Evaluate Effect of a Single Dose of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Participants With Solid Tumors

A Phase 2, Open-Label, Pharmacodynamic Study to Evaluate the Effect of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Subjects With Solid Tumors

Blood samples were to be collected at baseline (Day 1, pre-dose) and at one timepoint between Day 14 and Day 28, and isotope dilution techniques used, to measure the change from baseline in red blood cell mass following a single dose of sotatercept.

Blood samples were collected at baseline (Day 1, pre-dose) and at one timepoint between Day 14 and Day 28, and isotope dilution techniques used, to measure the change from baseline in plasma volume following a single dose of sotatercept.

Blood samples were to be collected at baseline (Day 1, pre-dose) and at Day 211 to measure the change from baseline in absolute reticulocyte count.

Blood samples were collected at baseline (Day 1, pre-dose) and at Day 211 to measure the change from baseline in erythropoietin levels.

Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype A following a single dose of sotatercept.

Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype A2 following a single dose of sotatercept.

Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype C following a single dose of sotatercept.

An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

The safety analysis population included all participants who received at least one dose of study treatment. The analysis population for All-Cause Mortality included all enrolled participants.

Participants received a single 35 mg dose of sotatercept by SC injection on Day 1, Day 43, and Day 85.

Sotatercept 35 mg

Participants received a single 35 mg dose of sotatercept by subcutaneous (SC) injection on Day 1, Day 43, and Day 85.

Ethnicity (NIH/OMB)

No data were collected for Change from Baseline in Red Blood Cell Mass Following a Single Dose of Sotatercept.

Change From Baseline in Red Blood Cell Mass Following a Single Dose of Sotatercept

All participants who received at least one dose of study treatment and had data for Change from Baseline in Plasma Volume Following a Single Dose of Sotatercept

Change From Baseline in Plasma Volume Following a Single Dose of Sotatercept

No data were collected for Change from Baseline in Absolute Reticulocyte Count.

Change From Baseline in Absolute Reticulocyte Count

All participants who received at least one dose of study treatment and had data for Change from Baseline in Erythropoietin Levels

Change From Baseline in Erythropoietin Levels

All participants who received at least one dose of study treatment and had data for Change from Baseline in Hemoglobin Subtype A Following a Single Dose of Sotatercept

Change From Baseline in Hemoglobin Subtype A Following a Single Dose of Sotatercept

All participants who received at least one dose of study treatment and had data for Change from Baseline in Hemoglobin Subtype A2 Following a Single Dose of Sotatercept

Change From Baseline in Hemoglobin Subtype A2 Following a Single Dose of Sotatercept

All participants who received at least one dose of study treatment and had data for Change from Baseline in Hemoglobin Subtype C Following a Single Dose of Sotatercept

Change From Baseline in Hemoglobin Subtype C Following a Single Dose of Sotatercept

All participants who received at least one dose of study treatment.

Number of Participants Who Experienced One or More Adverse Events (AEs)

Heart and Blood Diseases

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Sotatercept 0.2 mg/kg will be administered every 21 days for 12 doses subcutaneously into the upper arm, abdomen or thigh.

0.2 mg/kg of normal saline will be administered subcutaneously in the upper arm, abdomen or thigh for 21 days for 12 doses.

Rebecca Silbermann, M.D.

Lytic bone disease continues to be one of the most devastating complications of multiple myeloma (MM) despite recent and dramatic advancements in MM management, and bone lesions persist and can continue to significantly impact a patient's morbidity, even when an individual's myeloma is otherwise under good control. To date, no agent has been shown to have a prolonged bone anabolic response in myeloma.

Preliminary studies treating healthy postmenopausal women with a single dose of sotatercept demonstrated a rapid and sustained increase in serum biochemical markers of bone formation and a decrease in markers of bone resorption. Similarly, the murine analog to sotatercept, RAP-011, increases bone mineral density and strength in murine studies of both normal animals and models of bone loss. We hypothesize that sotatercept will provide an anabolic response for bone in myeloma patients with bone disease.

A Phase IIa Study of Sotatercept on Bone Mass and Turnover in Patients With Multiple Myeloma

The presence of change in biochemical markers of bone turnover during treatment with sotatercept will be examined.

Change in bone mineral density of the femoral neck, forearm and spine.

The change in myeloma markers will be determined by quantifying immunoglobulins, SPEP, UPEP and free light chains.

Measure the change in size of target bone lesions using x-ray of target skeletal lesions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Patients With Metastatic Breast Cancer (MK-7962-012)	NCT00931606	Chemotherapy In...	Sotatercept Placebo	18 Years -	Merck Sharp & Dohme LLC
Study to Evaluate Effect of a Single Dose of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Participants With Solid Tumors	NCT01190644	Solid Tumors	Sotatercept	18 Years -	Merck Sharp & Dohme LLC
A Phase IIa Study of Sotatercept on Bone Mass and Turnover in Patients With Multiple Myeloma	NCT02230917	Multiple Myelom...	Sotatercept Placebo	18 Years -	Indiana University
Study of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Patients With Metastatic Breast Cancer (MK-7962-012)	NCT00931606	Chemotherapy In...	Sotatercept Placebo	18 Years -	Merck Sharp & Dohme LLC
Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)	NCT01736683	Anemia Myelodysplastic... Chronic Myelomo... Low to Intermed... Myelodysplastic... Chronic Myelomo...	Sotatercept	18 Years -	Merck Sharp & Dohme LLC
Study to Evaluate Effect of a Single Dose of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Participants With Solid Tumors	NCT01190644	Solid Tumors	Sotatercept	18 Years -	Merck Sharp & Dohme LLC
A Phase IIa Study of Sotatercept on Bone Mass and Turnover in Patients With Multiple Myeloma	NCT02230917	Multiple Myelom...	Sotatercept Placebo	18 Years -	Indiana University

Spots Global Cancer Trial Database for sotatercept

Every month we try and update this database with for sotatercept cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sotatercept

Every month we try and update this database with for sotatercept cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sotatercept cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.