NCT07672769尚未招募2 期
Bexmarilimab Plus Azacitidine in a Randomized, Double-blind, Placebo-controlled Phase IIb Trial in Treatment-naïve Higher-risk Myelodysplastic Syndromes (HR-MDS)
Faron Pharmaceuticals Ltd0 个研究点目标入组 90 人开始时间: 2026年10月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 90
- 主要终点
- Dose selection utility score 3-months from last participant enrollment utilising efficacy and safety components.
研究概览
简要总结
This Phase IIb study (BEXERA) will evaluate the safety and efficacy of bexmarilimab (FP-1305), an antibody targeting Clever-1, given in combination with azacitidine compared with azacitidine plus placebo in adults with treatment-naïve higher-risk myelodysplastic syndromes (HR-MDS). Participants will be randomized to receive bexmarilimab at one of two dose levels (1 mg/kg or 3 mg/kg) plus azacitidine, or placebo plus azacitidine. The primary aim is to select the recommended dose of bexmarilimab for subsequent development based on a predefined integration of clinical response and safety/tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Participant provides written informed consent.
- •Participant is ≥18 years of age.
- •Participant has newly diagnosed MDS with morphologically confirmed HR-MDS as defined according to 2022 World Health Organization classification (5th Edition, Annex 7).
- •IPSS-M classification of moderately high risk, high risk, and very high risk.
- •<20% bone marrow blasts per bone marrow biopsy/aspirate at screening
- •Participant is eligible for azacitidine per local practice and willing to initiate trial therapy.
- •Participant has ECOG performance score 0 to
- •Participant has life expectancy ≥3 months.
- •Participant has adequate organ function: creatinine clearance ≥30 mL/min (Cockcroft-Gault); indirect (unconjugated) bilirubin ≤1.5 times the upper limit of normal (ULN) (unless related to Gilbert's syndrome, in which case the indirect bilirubin levels must be <3×ULN for inclusion); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3×ULN.
- •Participant has baseline leukocyte count of <20×109/L. Hydroxycarbamide use is permitted to meet this criterion.
- •Women of childbearing potential have a negative pregnancy test; participants of childbearing potential (and their partners) agree to use highly effective contraception during treatment and for ≥6 months after last dose.
- •Participant is willing and able to comply with protocol procedures and follow up.
排除标准
- •Participant has a previous diagnosis of AML, has transformed to AML, or has MDS subtypes outside the scope or overlapping myeloid neoplasms: MDS evolved from pre-existing myeloproliferative neoplasms (MPN); MDS/MPN overlap (e.g., chronic myelomonocytic leukemia, acute chronic myeloid leukemia, juvenile myelomonocytic leukemia, unclassifiable); advanced myelofibrosis (MF Grade ≥3); or severe autoimmune hemolysis.
- •Participants who are considered appropriate candidates for immediate allogeneic haematopoietic stem cell transplantation (HSCT) at the time of screening are excluded, irrespective of transplant timing, donor availability, or planned bridging therapy. Determination of transplant candidacy should be based on institutional standards and routine clinical practice, including assessment of individual clinical factors such as age, performance status, comorbidities, organ function, disease risk, and donor suitability.
- •Participants with ≥20% blasts in peripheral blood or bone marrow or evidence of myeloid sarcoma (extramedullary AML).
- •Participant has a lack of screening cytogenetic data or demonstrated normal karyotype per local or central analysis, should the patient have <5% blasts at screening.
- •Participant has received previous lines of anticancer therapy for MDS (disease-modifying therapy), including HMAs (e.g., azacitidine, decitabine), chemotherapy, or HSCT. Supportive care (e.g., transfusions, growth factors) is permitted.
- •Participant has clinically significant cardiac disease: recent myocardial infarction within 12 months; symptomatic congestive heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction (LVEF) <40%; uncontrolled clinically significant arrhythmias; or congenital/familial long-QT syndrome or pre-excitation syndrome.
- •Participant has active, uncontrolled infection requiring IV antimicrobials; known active invasive fungal infection; uncontrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local standards.
- •Participant has known active central nervous system (CNS) involvement by myeloid malignancy
- •All prior allo-HSCT within 6 months before Screening; ongoing clinically significant graft versus host disease (GVHD) requiring systemic immunosuppression.
- •Participant has active autoimmune disease requiring systemic therapy or requiring ≥10 mg/day prednisone (or equivalent) within 14 days prior to first dose; topical/inhaled/ophthalmic steroids permitted. (Immune conditions such as type 1 diabetes, controlled thyroid disease, vitiligo, psoriasis, alopecia are not exclusions.)
- •Participant has clinically relevant hepatic disease (e.g., Child-Pugh C) or ALT/AST >3×ULN and bilirubin exceeding inclusion thresholds (indirect [unconjugated] bilirubin >1.5×ULN [unless related to Gilbert's syndrome, in which case the indirect bilirubin levels must be >3×ULN]); persistent chronic ulcers with high risk of infection per investigator's assessment.
- •Participant has received recent non-MDS related anticancer therapy or investigational agents within drug-specified washout periods (e.g., <21 days from last IV/SC cytotoxic, <14 days or <5 half-lives for small-molecule therapy, <4 weeks for other immunotherapies).
- •Participant has a history of another malignancy that is active, progressing, or has required systemic treatment within the past 2 years of screening, excluding non-melanoma skin cancer, carcinoma in situ treated with curative intent.
- •Participant has known uncontrolled human immunodeficiency virus, active hepatitis B virus, or hepatitis C virus with high-level viremia; participants with controlled viral infections on stable therapy may be eligible per local guidance.
- •Participant is pregnant or lactating.
- •Participant has prior exposure to bexmarilimab.
- •Participant has any condition, including psychiatric or substance-use disorder, that in the investigator's judgment would compromise informed consent, compliance, or interpretation of trial results.
- •Participant has a history of hypersensitivity to compounds related to immunotherapy or to any of their excipients.
- •Participant has undergone major surgery within 4 weeks of Cycle 1 Day 1.
研究组 & 干预措施
Bexmarilimab (3mg/kg) and azacitidine
Experimental
Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous.
干预措施: azacitidine (Drug)
Bexmarilimab (1mg/kg) and azacitidine
Experimental
Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous.
干预措施: bexmarilimab (1mg/kg) (Drug)
Bexmarilimab (3mg/kg) and azacitidine
Experimental
Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous.
干预措施: bexmarilimab (3mg/kg) (Drug)
Placebo and azacitidine
Placebo Comparator
Standard of care azacitidine as per label/institutional practice; Placebo weekly (Q1W), Intravenous.
干预措施: Placebo (Drug)
Placebo and azacitidine
Placebo Comparator
Standard of care azacitidine as per label/institutional practice; Placebo weekly (Q1W), Intravenous.
干预措施: azacitidine (Drug)
Bexmarilimab (1mg/kg) and azacitidine
Experimental
Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous.
干预措施: azacitidine (Drug)
结局指标
主要结局
Dose selection utility score 3-months from last participant enrollment utilising efficacy and safety components.
时间窗: 3 months from last participant enrollment
Dose-selection utility score at the end of the primary dose-selection assessment window (3 months from last participant enrollment), calculated per dose using a pre-specified algorithm that integrates: * Efficacy component (achievement of CR + CReq per IWG2023 criteria). * Safety/tolerability component (rate of treatment-related Grade 3-5 treatment-related adverse events \[TRAEs\]). For each arm, there will be an observed efficacy rate (PE) and toxicity rate (PT) and the utility score will be defined as U = PE - ωPT where the ω is a pre-specified weight.
次要结局
- Complete Remission (CR) defined by IWG2006(36 months from enrollment)
- Complete Remission (CR) and Complete Remission Equivalent (CReq)(36 months from enrollment)
- Composite Complete Remission (cCR) defined by IWG2023(36 months from enrollment)
- Overall Response Rate (ORR)(36 months from enrollment)
- Overall Survival (OS)(36 months from enrollment)
- Event Free Survival (EFS)(36 months from enrollment)
- Reporting of frequency and severity of adverse events (AEs), serious adverse events (SAE) and laboratory abnormalities(36 months from enrollment)
- Time to response(36 months from enrollment)
- Duration of Response (DOR)(36 months from enrollment)
- Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent (TD) at Baseline(36 months from enrollment)
- Time to transformation to AML(36 months from enrollment)
- Rate of Allogeneic hematopoietic stem cell transplantation (allo-HSCT)(36 months from enrollment)
- Number of infections and hospitalizations(36 months from enrollment)
- To characterize the pharmacokinetic (PK) profile of bexmarilimab plus azacitidine at two bexmarilimab doses(36 months from enrollment)
- To characterize the immunogenicity profile of bexmarilimab plus azacitidine at two bexmarilimab doses(36 months from enrollment)
- To characterize the pharmacodynamic (PD) profile of bexmarilimab plus azacitidine at two bexmarilimab doses(36 months from enrollment)
研究者
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