A Phase Ib, Multicenter, Open-label Platform Study of Select Drug Combinations in Adult Patients With Lower Risk (Very Low, Low, or Intermediate Risk) Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 33
- 试验地点
- 6
- 主要终点
- Incidence of DLTs
研究概览
简要总结
The purpose of this study was to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS.
详细描述
This was a phase Ib, multi center, open-label, platform study with multiple treatment arms.
The design of this study was adaptive to allow discontinuation of poorly tolerated or ineffective treatments and to facilitate the introduction of new candidate single agents or combinations. Study design included a dose escalation/confirmation part and a dose expansion.
The planned initial single agent and combination treatment arms were the following:
- Arm 1: MBG453 single agent
- Arm 2: NIS793 single agent
- Arm 3: canakinumab single agent
- Arm 4: MBG453 + NIS793 combination
- Arm 5: MBG453 + canakinumab combination Patients were treated in the dose confirmation/escalation part of the study in Arms 1, 2, 3 and 5. No patients were treated in Arm 4. The study did not progress into the expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Signed informed consent must be obtained prior to participation in the study.
- •Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
- •Patients must have a diagnosis prior to participation in the study of IPSS-R very low, low, or intermediate risk MDS with ≤10% bone marrow blasts and one or more of the following:
- •Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is refractory to ESAs (or the patient is intolerant to ESAs)
- •Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level ≥ 500 /uL
- •Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL
- •Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent and/or severe infections and an ANC that is <1000/ µL and amenable to response assessments by International Working Group (IWG) response criteria in myelodysplasia (Cheson et al 2006)
- •Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC therapeutic options including lenalidomide
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
- •Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions' guidelines and be willing to undergo a bone marrow aspirate and/or biopsy at screening, during and at the end of therapy on this study -
排除标准
- •Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
- •History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
- •Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
- •Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or ESAs anytime ≤ 2 weeks (or 5 half-lives, whichever is longer) prior to start of study treatment.
- •Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
- •For arms containing canakinumab: Patients with ANC < 500 /µL
研究组 & 干预措施
Arm 1: MBG453 single agent
Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.
干预措施: MBG453 (Drug)
Arm 2: NIS793 single agent
Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.
干预措施: NIS793 (Drug)
Arm 3: canakinumab single agent
Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.
干预措施: canakinumab (Drug)
Arm 4: MBG453 + NIS793 combination
Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.
干预措施: MBG453 (Drug)
Arm 4: MBG453 + NIS793 combination
Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.
干预措施: NIS793 (Drug)
Arm 5: MBG453 + canakinumab combination
Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.
干预措施: MBG453 (Drug)
Arm 5: MBG453 + canakinumab combination
Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.
干预措施: canakinumab (Drug)
结局指标
主要结局
Incidence of DLTs
时间窗: 30 Months
Incidence of dose limiting toxicities (DLTs) during the first 2 cycle of treatment during the dose escalation/confirmation part
Dose interruption reduction
时间窗: 30 Months
Dose tolerability
Dose intensity
时间窗: 30 Months
Dose tolerability
AE and SAE incidence
时间窗: 30 months
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment
次要结局
- Reduction in red blood cell (RBC) / platelet transfusions from baseline in transfusion dependent patients(Baseline, 30 Months)
- Change from baseline in hemoglobin (Hb) in transfusion dependent and transfusion independent patients(Baseline, 30 Months)
- Change from baseline in platelet count in transfusion dependent and transfusion independent patients(Baseline, 30 Months)
- Best Overall Response (BOR) in transfusion dependent and transfusion independent patients(30 Months)
- Duration of transfusion independence lasting for >=8 weeks, >=12 weeks, >=16 weeks, >=24 weeks in transfusion dependent patients(30 Months)
- Change from baseline in Absolute Neutrophil Count/White Blood Cells (ANC/WBC) in transfusion dependent and transfusion independent patients(Baseline, 30 Months)
- Time to onset of BOR in transfusion dependent and transfusion independent patients(30 Months)
- Progression free survival (PFS) in transfusion dependent and transfusion independent patients(30 Months)
- Time to progression (TTP) in transfusion dependent and transfusion independent patients(30 Months)
- Characterize pharmacokinetics for single agents and combinations: Ctrough(30 Months)
- Time to onset of transfusion independence in transfusion dependent patients(30 Months)
- Duration of Response (DOR) in transfusion dependent and transfusion independent patients(30 Months)
- Characterize the prevalence of immunogenicity(30 Months)
- Overall Response Rate (ORR) in transfusion dependent and transfusion independent patients(30 Months)
- Characterize pharmacokinetics for single agents and combinations: Cmax(30 Months)
- Characterize pharmacokinetics for single agents and combinations: Tmax(30 Months)