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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 26
- 主要终点
- Number of Participants Who Experienced a Hematopoietic Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women >18 years of age
- •Part 1: Histologically confirmed (cytology or biopsy) solid tumor malignancy, excluding those solid tumors treated with curative intent.
- •Part 2: Histologically confirmed non-small cell lung cancer
- •Documented metastatic disease
- •Measurable or non-measurable disease evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- •All of the following laboratory values:
- •Hemoglobin ≥6.5 to <11.0 g/dL (≥65 to <110 g/L), due to chemotherapy-induced anemia
- •Absolute neutrophil count ≥500/mm^3
- •Platelet count ≥75,000/mm^3 (>2 hours since prior platelet transfusion
- •Adequate renal function
- •creatinine clearance ≥40mL/min or ≥50 mL/min if cisplatin is concomitantly administered and
- •urine protein / creatinine ratio ≤1.0; or ≤2.0 if bevacizumab (Avastin®) is concomitantly administered
- •Hepatic function (bilirubin <1.5 x upper limits of normal (ULN); AST and ALT <3.0 x ULN and ≤5.0 ULN for participants with liver metastases)
- •Participants must have received:
- •at least one cycle and up to 4 cycles (q3w schedule) of platinum-based chemotherapy and be randomized prior to receiving Cycle 5 OR
- •at least one cycle and up to 3 months (depending upon regimen) of platinum-based chemotherapy
- •>28 days since previous treatment with ESA
- •>14 days since last red blood cell transfusions
- •Eastern Oncology Cooperative Group (ECOG) Performance status 0-2
- •For females of childbearing potential, highly effective method of birth control for at least 28 days before starting study, during participation and at least 112 days following last dose of sotatercept
- •Males must use latex condom or non-latex condom not made of (animal) membrane during any sexual contact with female of childbearing potential
- •Life expectancy of >3 months
- •Willing to adhere to study visit schedule
- •Understand and voluntarily sign informed consent
排除标准
- •Part 2 only, history of prior regimen(s)of platinum-based chemotherapy for metastatic NSCLC and/or history of adjuvant platinum-based chemotherapy with last dose received less than six months prior to the start of current first-line platinum-based chemotherapy for metastatic NSCLC.
- •National Cancer Institute Common Terminology for Adverse Events Grade >3 toxicity
- •Prior radiation to >20% of whole skeleton
- •Prior regimen(s) of platinum based chemotherapy for metastatic disease and/or history of adjuvant platinum-based chemotherapy with the last dose received less than six months prior to the start of current first-line platinum-based chemotherapy for metastatic disease
- •Central nervous system metastases
- •Clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic, or genitourinary disease unrelated to underlying malignancy
- •Classification of 3 or higher heart failure (as classified by New York Heart Association)
- •History of thrombosis, deep vein thrombosis, pulmonary emboli, or embolic stroke, if not stable on anticoagulants and/or one of these events occurring in past 6 months
- •Diagnosis of a myeloid malignancy or known history of myelodysplasia
- •Recent history (within 14 days of Day 1) of IV/oral antibiotics due to post septic episode
- •Uncontrolled hypertension. Controlled hypertension is considered clinically stable, and systolic blood pressure (SBP) must be <150 mmHg and diastolic blood pressure (DBP) must be < 00 mmHg.
- •Known human immunodeficiency virus (HIV)
- •Known active hepatitis B or C antibody
- •Iron deficiency
- •History of anemia as a result of inherited hemoglobinopathy
- •History of anemia due to autoimmune or hereditary hemolysis or gastrointestinal bleeding
- •Received treatment with another investigational drug or device within 28 days prior to Day 1, or if the half life of the previous product is known, within 5 times the half life prior to dosing, whichever may be longer.
- •Any prior use of sotatercept.
- •Pregnant or lactating females or females planning to become pregnant
- •History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (Refer to the Investigator's Brochure for further information).
- •Major surgery within 30 days prior to Day 1 (participants must have completely recovered from any previous surgery prior to Day 1).
研究组 & 干预措施
Sotatercept 15 mg
Participants will receive sotatercept 15 mg by subcutaneous (SC) injection once every 42 days, up to four doses.
干预措施: Sotatercept 15 mg (Drug)
Sotatercept 30 mg
Participants will receive sotatercept 30 mg by SC injection once every 42 days, up to four doses.
干预措施: Sotatercept 30 mg (Drug)
结局指标
主要结局
Number of Participants Who Experienced a Hematopoietic Response
时间窗: Up to Day 28
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.
次要结局
- Progression Free Survival (PFS)(Up to 12 months)
- Area Under the Concentration Versus Time Curve From Time 0 to 28 Days (AUC0-28d) of Sotatercept Following a Single Dose(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 28)
- Apparent Serum Clearance (CL/F) of Sotatercept Following a Single Dose(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43)
- Overall Response Rate (ORR)(Up to 12 months)
- Number of Participants Who Experienced One or More Adverse Events (AEs)(Up to approximately 6 months)
- Time to Progression (TTP)(Up to 6 months)
- Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of Sotatercept Following a Single Dose(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43)
- Time to Maximum Concetration (Tmax) of Sotatercept Following a Single Dose(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43)
- Overall Survival (OS)(Up to 24 months)
- Number of Participants Who Experienced an Improvement in Quality of Life Scores(Up to 6 months)
- Maximum Plasma Concentration (Cmax) of Sotatercept Following a Single Dose(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43)
- Apparent Terminal Half-life (t1/2) of Sotatercept Following a Single Dose(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43)
- Apparent Volume of Distribution (Vz/F) Following a Single Dose of Sotatercept(Pre-dose 1 Day 1, 4 hours post-dose Day 1, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, pre-dose 2 Day 43)