Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Blood and Lymph Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Urinary Bladder Neoplasms

Uterine Cervical Neoplasms

Anemia

Head and Neck Neoplasms

Carcinoma, Small Cell

Small Cell Lung Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Hematologic Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Participants will receive sotatercept 15 mg by subcutaneous (SC) injection once every 42 days, up to four doses.

Participants will receive sotatercept 30 mg by SC injection once every 42 days, up to four doses.

Sotatercept 15 mg SC injection once every 42 days, up to four doses

Sotatercept 15 mg

Sotatercept 30 mg SC injection once every 42 days, up to four doses

Sotatercept 30 mg

Medical Director

The purpose of this study was to determine an effective and safe dose of sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia (CIA) in participants with metastatic non-small cell lung cancer (NSCLC) who are being treated with first-line platinum based chemotherapy.

The ACE-011-NSCL-001 Phase 2a study was an open-label, randomized, dose-ranging study designed to assess the efficacy, safety, tolerability, pharmacokinetic and quality of life of sotatercept for treatment of CIA in participants with advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens. Other objectives included the effect of sotatercept treatment on bone metabolism, the evaluation of the expression of Activin A and other proteins/biomarkers (including myostatin and follistatin) and the assessment of renal function biomarkers. The study consisted of a Screening Period, a Treatment Period of approximately 6 months (up to 4 doses of sotatercept at either 15 mg or 30 mg administered subcutaneously every 42 days) and a Post-treatment Follow-up Period or End of Treatment (42 days after the last dose of sotatercept). The study was terminated early due to a slower than expected rate of enrollment as a result of substantial changes in the standard of care for cancer participants with anemia which resulted in challenges to timely accrual and completion of the study. Therefore, 26 participants were randomized into the study and the planned Part 2 of the study consisting of a double-blind, randomized, placebo-controlled Phase 2b/3 study conducted at the optimal dose of sotatercept in up to 750 participants with metastatic NSCLC was not performed. Due to the small sample size and variability of the data, changes were made to modify the study endpoints and revise them to be exploratory only.

To Determine Safe and Effective Dose of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Participants With Advanced Non-small Cell Lung Cancer

An Open-Label Randomized, Phase 2A, Dose-Ranging Study of Sotatercept (ACE-011) for Chemotherapy-Induced Anemia in Subjects With Advanced or Metastatic Solid Tumors Treated With Platinum-Based Chemotherapeutic Regimens

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

A hematopoietic response was defined as an increase in a participant's hemoglobin (Hgb) of ≥1.0 g/dL above the study baseline value for 4 consecutive weeks, in the absence of red blood cell transfusion and/or erythropoiesis-stimulating agents.

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.

TTP was defined as the time from date of randomization to date of diagnosis of progressive disease

PFS was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first

OS was defined as the time between randomization and death

Overall Response was defined as the percentage of participants who achieved an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 guidelines. CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing.

Participants were to be assessed on improvement of quality of life using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4.0) and the Lung Cancer Symptom Scale (LCSS). The FACIT Fatigue score ranges from 0 to 52, with 0 representing the best outcome and 52 representing the worst outcome. The LCSS is a 9-item patient-rated scale, 6 of which measure major symptoms (loss of appetite, fatigue, cough, dyspnoea, pain, and haemoptysis), and 3 of which are summation items related to total symptomatic distress, activity, and overall quality of life. Participants responses are measured using the mean score on the 9-item visual analogue scales, with 100-mm lines, with 0 representing the best outcome and 100 representing the worst outcome.

AUC0-28d is a measure of the mean concentration levels of a drug in the plasma from time 0 to 28 days.

AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time.

Cmax is a measure of the maximum amount of drug in the plasma after a dose is given.

Tmax is a measure of the time it takes for a drug to reach maximum concentration in the plasma after the dose is given.

t1/2 is the elimination half-life of study drug: the time it takes for half of the study drug in the blood plasma to dissipate.

Apparent serum CL is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

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 enrolled participants.

Participants received sotatercept 15 mg by SC injection once every 42 days, up to four doses.

Participants received sotatercept 30 mg by SC injection once every 42 days, up to four doses.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Senior Vice President, Global Clinical Development

All participants who received at least 1 dose of study drug

Number of Participants Who Experienced a Hematopoietic Response

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

TTP was to be analyzed in Part 2 of the study. Due to low enrollment, the study was terminated early and Part 2 was not performed.

Time to Progression (TTP)

PFS was to be analyzed in Part 2 of the study. Due to low enrollment, the study was terminated early and Part 2 was not performed.

Progression Free Survival (PFS)

OS was to be analyzed in Part 2 of the study. Due to low enrollment, the study was terminated early and Part 2 was not performed.

Overall Survival (OS)

ORR was to be analyzed in Part 2 of the study. Due to low enrollment, the study was terminated early and Part 2 was not performed.

Overall Response Rate (ORR)

Quality of Life parameters were to be analyzed in Part 2 of the study. Due to low enrollment, the study was terminated early and Part 2 was not performed.

Number of Participants Who Experienced an Improvement in Quality of Life Scores

All participants who received at least 1 dose of study treatment and had data for AUC0-28d of Sotatercept Following a Single Dose

Area Under the Concentration Versus Time Curve From Time 0 to 28 Days (AUC0-28d) of Sotatercept Following a Single Dose

All participants who received at least 1 dose of study treatment and had data for AUC0-inf of Sotatercept Following a Single Dose

Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of Sotatercept Following a Single Dose

All participants who received at least 1 dose of study treatment and had data for Cmax of Sotatercept Following a Single Dose

Maximum Plasma Concentration (Cmax) of Sotatercept Following a Single Dose

All participants who received at least 1 dose of study treatment and had data for Tmax of Sotatercept Following a Single Dose of Sotatercept

Time to Maximum Concetration (Tmax) of Sotatercept Following a Single Dose

All participants who received at least 1 dose of study treatment and had data for t1/2 of Sotatercept Following a Single Dose

Apparent Terminal Half-life (t1/2) of Sotatercept Following a Single Dose

All participants who received at least 1 dose of study treatment and had data for CL/F of Sotatercept Following a Single Dose

Apparent Serum Clearance (CL/F) of Sotatercept Following a Single Dose

All participants who received at least 1 dose of study treatment and had data for Vz/F of Sotatercept Following a Single Dose

Apparent Volume of Distribution (Vz/F) Following a Single Dose of Sotatercept

Participants received sotatercept 15 mg by subcutaneous (SC) injection once every 42 days, up to four doses.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
To Determine Safe and Effective Dose of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Participants With Advanced Non-small Cell Lung Cancer	NCT01284348	Anemia Carcinoma, Non-... Carcinoma, Smal... Bladder Cancer Cancer of Head ... Uterine Cervica...	Sotatercept 15 ... Sotatercept 30 ...	18 Years -	Merck Sharp & Dohme LLC
To Determine Safe and Effective Dose of Sotatercept for the Treatment of Chemotherapy Induced Anemia in Participants With Advanced Non-small Cell Lung Cancer	NCT01284348	Anemia Carcinoma, Non-... Carcinoma, Smal... Bladder Cancer Cancer of Head ... Uterine Cervica...	Sotatercept 15 ... Sotatercept 30 ...	18 Years -	Merck Sharp & Dohme LLC

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