NCT00931606

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

Terminated Phase 2 Results posted Last updated 13 September 2023

What this trial tests

Phase 2 trial testing Sotatercept in Chemotherapy Induced Anemia in 30 participants. Terminated before completion.

Timeline

1 June 2009

Primary endpoint
18 November 2010

18 November 2010

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	30
Start date	1 June 2009
Primary completion	18 November 2010
Estimated completion	18 November 2010
Sites	35 locations across Russia, United States

Drugs / interventions tested

• Sotatercept (SOTATERCEPT) — full drug profile →
• Placebo

Conditions studied

• Chemotherapy Induced Anemia — all drugs for Chemotherapy Induced Anemia →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, female only, with Chemotherapy Induced Anemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieved a Hematopoietic Response Primary · Baseline and Up to ~145 Days

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.

Overall

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 52.2
Sotatercept 0.3 mg/kg	33.3	7.5 – 70.1
Sotatercept 0.5 mg/kg	50.0	6.8 – 93.2
Placebo	20.0	0.5 – 71.6
All Sotatercept-treated Participants	27.8	9.7 – 53.5

Received weekly chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 84.2
Sotatercept 0.3 mg/kg	0	0 – 84.2
Sotatercept 0.5 mg/kg	25.0	2.5 – 100.0
Placebo	20	2.5 – 100.0
All Sotatercept-treated Participants	5.6	0.5 – 71.6

Received less frequent chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 70.8
Sotatercept 0.3 mg/kg	33.3	9.9 – 81.6
Sotatercept 0.5 mg/kg	25.0	0.8 – 90.6
Placebo	0	0 – 60.2
All Sotatercept-treated Participants	22.2	9.1 – 61.4

Number of Participants Who Experienced an Adverse Event (AE) Secondary · Up to ~175 Days

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.

Group	Value	95% CI
Sotatercept 0.1 mg/kg	6
Sotatercept 0.3 mg/kg	7
Sotatercept 0.5 mg/kg	7
Placebo	5

Number of Participants Who Discontinued Study Intervention Due to an Adverse Event Secondary · Up to ~85 Days

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.

Group	Value	95% CI
Sotatercept 0.1 mg/kg	1
Sotatercept 0.3 mg/kg	0
Sotatercept 0.5 mg/kg	4
Placebo	1

Percentage of Participants Achieving an Increase From Baseline Hemoglobin of ≥ 2 g/dL Secondary · Baseline and Up to ~145 Days

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.

Overall

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 52.2
Sotatercept 0.3 mg/kg	11.1	0.3 – 48.2
Sotatercept 0.5 mg/kg	0	0 – 60.2
Placebo	0	0 – 52.2
All Sotatercept-treated Participants	5.6	0.1 – 27.3

Received weekly chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 84.2
Sotatercept 0.3 mg/kg	0	0 – 84.2
Sotatercept 0.5 mg/kg	0	0 – 97.5
Placebo	0	0 – 97.5
All Sotatercept-treated Participants	0	0 – 52.2

Received less frequent chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 70.8
Sotatercept 0.3 mg/kg	11.1	0.4 – 57.9
Sotatercept 0.5 mg/kg	0	0 – 70.8
Placebo	0	0 – 60.2
All Sotatercept-treated Participants	5.6	0.2 – 36.0

Percentage of Participants Achieving an Increase From Baseline Hemoglobin ≥ 11 g/dL Secondary · Baseline and Up to ~145 Days

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.

Overall

Group	Value	95% CI
Sotatercept 0.1 mg/kg	20.0	0.5 – 71.6
Sotatercept 0.3 mg/kg	22.2	2.8 – 60.0
Sotatercept 0.5 mg/kg	75.0	19.4 – 99.4
Placebo	20.0	0.5 – 71.6
All Sotatercept-treated Participants	33.3	13.3 – 59.0

Received weekly chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 84.2
Sotatercept 0.3 mg/kg	11.1	1.3 – 98.7
Sotatercept 0.5 mg/kg	25.0	2.5 – 100.0
Placebo	20.0	2.5 – 100.0
All Sotatercept-treated Participants	11.1	5.3 – 85.3

Received less frequent chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	20.0	0.8 – 90.6
Sotatercept 0.3 mg/kg	11.1	0.4 – 57.9
Sotatercept 0.5 mg/kg	50.0	9.4 – 99.2
Placebo	0	0 – 60.2
All Sotatercept-treated Participants	22.2	9.1 – 61.4

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

Overall

Group	Value	95% CI
Sotatercept 0.1 mg/kg	20.0	0.5 – 71.6
Sotatercept 0.3 mg/kg	22.2	2.8 – 60.0
Sotatercept 0.5 mg/kg	75.0	19.4 – 99.4
Placebo	20.0	0.5 – 71.6
All Sotatercept-treated Participants	33.3	13.3 – 59.0

Received weekly chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	0	0 – 84.2
Sotatercept 0.3 mg/kg	11.1	1.3 – 98.7
Sotatercept 0.5 mg/kg	25.0	2.5 – 100.0
Placebo	20.0	2.5 – 100.0
All Sotatercept-treated Participants	11.1	5.3 – 85.3

Received less frequent chemotherapy and showed a response

Group	Value	95% CI
Sotatercept 0.1 mg/kg	20.0	0.8 – 90.6
Sotatercept 0.3 mg/kg	11.1	0.4 – 57.9
Sotatercept 0.5 mg/kg	50.0	9.4 – 99.2
Placebo	0	0 – 60.2
All Sotatercept-treated Participants	22.2	9.1 – 61.4

Duration of Hematopoietic Response for Hemoglobin ≥ 1 g/dL Secondary · Baseline and Up to ~145 Days

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.

Group	Value	95% CI
Sotatercept 0.3 mg/kg	47.0	± 20.30
Sotatercept 0.5 mg/kg	46.5	± 14.85
Placebo	29.0	± NA

Duration of Hematopoietic Response for Hemoglobin ≥ 2 g/dL Secondary · Baseline and Up to ~145 Days

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.

Group	Value	95% CI
Sotatercept 0.3 mg/kg	69.0	± NA

Duration of Hematopoietic Response for Hemoglobin ≥ 11 g/dL Secondary · Baseline and Up to ~145 Days

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.

Group	Value	95% CI
Sotatercept 0.3 mg/kg	41.0	± NA
Sotatercept 0.5 mg/kg	50.0	± 9.90
Placebo	29.0	± NA

Duration of Hematopoietic Response for Hemoglobin Increases ≥ 1 g/dL and/or Hemoglobin Concentration ≥ 11 g/dL Secondary · Baseline and Up to ~145 Days

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.

Group	Value	95% CI
Sotatercept 0.3 mg/kg	47.0	± 20.30
Sotatercept 0.5 mg/kg	50.0	± 9.90
Placebo	29.0	± NA

Duration of Hematopoietic Response for Hemoglobin Increases ≥ 2 g/dL, and/or Hemoglobin Concentration ≥ 11 g/dL Secondary · Baseline and Up to ~145 Days

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.

Group	Value	95% CI
Sotatercept 0.3 mg/kg	69.0	± NA
Sotatercept 0.5 mg/kg	50.0	± 9.90
Placebo	29.0	± NA

Time to Achieve Hematopoietic Response of Hemoglobin ≥ 1 g/dL Increase From Baseline Secondary · Baseline and Up to ~145 Days

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.

Group	Value	95% CI
Sotatercept 0.3 mg/kg	NA	72.0 – NA
Sotatercept 0.5 mg/kg	NA	6.0 – NA
Placebo	NA	112 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 281. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sotatercept 0.1 mg/kg

Serious: 0/8 (0%)

Deaths: 1/8

Sotatercept 0.3 mg/kg

Serious: 2/10 (20%)

Deaths: 3/10

Sotatercept 0.5 mg/kg

Serious: 3/7 (43%)

Deaths: 3/7

Placebo

Serious: 1/5 (20%)

Deaths: 0/5

Total

Serious: 6/30 (20%)

Deaths: 7/30

Serious adverse events (14 terms)

Reaction	System	Sotatercept 0.1 mg/kg	Sotatercept 0.3 mg/kg	Sotatercept 0.5 mg/kg	Placebo	Total
Nausea	Gastrointestinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Gastric ulcer perforation	Gastrointestinal disorders	—	—	—	—	—
Peptic ulcer	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—	—
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—

Other adverse events (136 terms — click to expand)

Reaction	System	Sotatercept 0.1 mg/kg	Sotatercept 0.3 mg/kg	Sotatercept 0.5 mg/kg	Placebo	Total
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Disturbance in attention	Nervous system disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Hypoaesthesia	Nervous system disorders	—	—	—	—	—
Dysuria	Renal and urinary disorders	—	—	—	—	—
Atelectasis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—
Nodal arrhythmia	Cardiac disorders	—	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—

Most-reported serious reactions: Nausea, Vomiting, Dehydration, Breast cancer metastatic, Anaemia, Gastric ulcer perforation, Peptic ulcer, Asthenia.

Data from ClinicalTrials.gov NCT00931606 adverse events section.

Sponsor's own description

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).

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Bone morphogenetic protein receptor signal transduction in human disease.
   Gomez-Puerto MC, Iyengar PV, García de Vinuesa A, Ten Dijke P, et al · · 2019 · cited 172× · PMID 30246251 · DOI 10.1002/path.5170
2. TGF-beta signal transduction: biology, function and therapy for diseases.
   Tie Y, Tang F, Peng D, Zhang Y, et al · · 2022 · cited 97× · PMID 36534225 · DOI 10.1186/s43556-022-00109-9
3. Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies.
   Raftopoulos H, Laadem A, Hesketh PJ, Goldschmidt J, et al · · 2016 · cited 51× · PMID 26370220 · DOI 10.1007/s00520-015-2929-9
4. TGFβ and activin A in the tumor microenvironment in colorectal cancer.
   Zessner-Spitzenberg J, Thomas AL, Krett NL, Jung B. · · 2019 · cited 11× · PMID 32154442 · DOI 10.1016/j.genrep.2019.100501