NCT02607813终止1 期
A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 142
- 试验地点
- 5
- 主要终点
- Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only)
研究概览
简要总结
A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.
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
- •All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Presence of at least one measurable lesion according to RECIST v1.
- •Documented MAPK alteration
- •Additional inclusion criteria for the Dose Expansion part: LXH254 in combination with PDR001:
- •Patients with confirmed KRAS-mutated NSCLC
- •Patients with confirmed NRAS-mutated melanoma (cutaneous melanoma only)
排除标准
- •Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled in the dose expansion part.
- •Exceptions may be made after documented agreement between Novartis and Investigator.
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- •Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- •Patients receiving proton pump inhibitors which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- •Pregnant or nursing (lactating) women
- •Additional exclusion criteria for LXH254 in combination with PDR001
- •History of severe hypersensitivity reactions, which in the opinion of the investigator may cause in increased risk of serious infusion reaction.
- •Known human immunodeficiency virus (HIV).
- •Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
- •Active, known or suspected autoimmune disease.
- •Active infection requiring systemic antibiotic therapy
- •Patients requiring systemic steroid therapy or any immunosuppressive therapy (≥10mg/day prednisone or equivalent) which cannot be discontinued at least 7 days prior to first dose of study treatment.
- •Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
- •Other inclusion/exclusion criteria as per protocol may apply.
研究组 & 干预措施
Dose expansion LXH254: Group 2
Experimental
干预措施: LXH254 (Drug)
Dose escalation LXH254
Experimental
干预措施: LXH254 (Drug)
Dose expansion LXH254: Group 1
Experimental
干预措施: LXH254 (Drug)
Dose expansion LXH254: Group 3
Experimental
干预措施: LXH254 (Drug)
Dose expansion: LXH254 + PDR001
Experimental
干预措施: LXH254 (Drug)
Dose expansion: LXH254 + PDR001
Experimental
干预措施: PDR001 (Drug)
Dose escalation LXH254 + PDR001
Experimental
干预措施: LXH254 (Drug)
Dose escalation LXH254 + PDR001
Experimental
干预措施: PDR001 (Drug)
结局指标
主要结局
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only)
时间窗: 56 days
cycle =28 days
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only)
时间窗: 28 days
cycle = 28 days
Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity.
时间窗: From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)
cycle = 28 days
次要结局
- Derived PK parameters of LXH254: half-life (T1/2)(Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Progression-free survival (PFS)(Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months)
- Plasma concentrations of PDR001(Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1)
- Derived PK parameters of LXH254: Peak Plasma Concentration (Cmax)(Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor tissue and in blood(Cycle 1 day 1, 2, 3, 15, and 16; upon disease progression (expected duration approximately 12 months))
- Derived PK parameters of PDR001: Time to Peak Plasma Concentration (Tmax)(Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1)
- Disease control rate (DCR)(Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months)
- Overall survival (OS) - only for dose expansion(From time of start treatment until the date of death; expected duration approximately 12 months)
- Plasma concentrations of LXH254(Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Derived PK parameters of LXH254: Area Under the Curve (AUC)(Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Overall response rate (ORR)(Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months)
- Duration of response (DoR)(Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months)
- Derived PK parameters of LXH254: Time to Peak Plasma Concentration (Tmax)(Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1)
- Derived PK parameters of PDR001: Area Under the Curve (AUC)(Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1)
- Derived PK parameters of PDR001: Peak Plasma Concentration (Cmax)(Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1)
- Derived PK parameters of PDR001: half-life (T1/2)(Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1)
研究者
研究点 (5)
Loading locations...
相似试验
已完成
1 期
ovartis sponsored Phase 1 studyJPRN-jRCT2080223169ovartis Pharma. K.K.9
已完成
不适用
A phase I dose finding study of oral LXH254 in adult patients with advanced solid tumors harboring MAPK pathway alterations.NL-OMON50657ovartis Pharma BV20
终止
1 期
A Phase Ib Study of LXH254-centric Combinations in NSCLC or MelanomaMelanomaNon-Small Cell Lung CancerNCT02974725Novartis Pharmaceuticals241
进行中（未招募）
2 期
Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic MelanomaMelanomaNCT04417621Novartis Pharmaceuticals134
尚未招募
1 期
A Study of QL1706H in Patients With Advanced Solid TumorsAdvanced Solid TumorsNCT06047431Qilu Pharmaceutical Co., Ltd.150