NCT03891953进行中（未招募）1 期
A Phase I/Ib, Open-label, Multi-center, Study of DKY709 as a Single Agent and in Combination With PDR001 in Patients With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 98
- 试验地点
- 4
- 主要终点
- incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is a phase I/Ib, open label study. The escalation portion will characterize the safety and tolerability of DKY709 and DKY709 in combination with PDR001 in subjects with NSCLC or melanoma who have received prior anti-PD-1/PD-L1 therapy, or subjects with NPC. After the determination of the MTD/RD for a particular treatment arm, dose expansion will further assess safety, tolerability, PK/PD, and anti-tumor activity of each regimen at the MTD/RD.
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 100 Years（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 informed consent form (ICF) signature.
- •Patients with advanced/metastatic cancer who have progressed despite having received standard therapy in the metastatic setting or are intolerant to standard therapy, and for whom no effective standard therapy is available
- •In expansion: patient with measurable disease as determined by RECIST version 1.1,
- •Dose escalation, patients must fit into one of the following groups:
- •NSCLC, previously treated with an anti-PD-1/PD-L1 therapy
- •Cutaneous Melanoma, previously treated with an anti-PD-1/PD-L1 therapy
- •Dose expansion part, patients must fit into one of the following groups:
- •NSCLC with historic documentation of PD-L1 ≥ 1%. Patients must have progressive disease after having experienced at least 4 months of investigator-assessed disease stability or response on prior anti-PD-L1-containing therapy
- •Cutaneous Melanoma, previously treated with anit-PD-1/PD-L1 therapy. Patients should have documented progression following anti-PD-1/PD-L1 therapy.
- •NPC, naive to anti-PD-1/PD-L1 therapy
- •mssCRC, naive to anti-PD-1/PD-L1 therapy
- •TNBC, naive to anti-PD-1/PD-L1 therapy
- •ECOG Performance Status ≤ 1
- •Patients must have a site of disease amenable to core needle biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline, and during therapy on the study. Exceptions may be considered after documented discussion with Novartis.
排除标准
- •Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated brain metastases should be neurologically stable for at least 4 weeks prior to study entry and off steroids for at least 2 weeks before administration of any study treatment.
- •History of severe hypersensitivity reactions to any ingredient of study drug(s) or other mAbs and/or their excipients.
- •Patient with out of range laboratory values defined as:
- •Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40 mL/min
- •Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
- •Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT > 5 x ULN
- •Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST > 5 x ULN
- •Absolute neutrophil count (ANC) < 1.0 x 109/L
- •Platelet count < 75 x 109/L (growth factor or transfusion support may not be used to meet entry criterion)
- •Hemoglobin (Hgb) < 8 g/dL (growth factor or transfusion support may not be used to meet entry criterion)
- •Magnesium, calcium or phosphate abnormality CTCAE > grade 1
- •Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility criteria is acceptable
- •Clinically significant cardiac disease or impaired cardiac function, including any of the following:
- •Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
- •On screening: QTcF > 450 msec (male), or > 460 msec (female)
- •QTc not assessable
- •Congenital long QT syndrome
- •History of familial long QT syndrome or known family history of as Torsades de Pointes
- •Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry
研究组 & 干预措施
DKY709
Experimental
DKY709 monotherapy
干预措施: DKY709 (Drug)
DKY709 + PDR001
Experimental
Combination therapy with DKY709 and PDR001
干预措施: DKY709 (Drug)
DKY709 + PDR001
Experimental
Combination therapy with DKY709 and PDR001
干预措施: PDR001 (Drug)
结局指标
主要结局
incidence of Dose Limiting Toxicities (DLTs)
时间窗: 1 Month
The incidence of DLTs during the first cycle of treatment with single agent DKY709 or the combination of DKY709 with PDR001.
Safety of DKY709 single agent treatment or DKY709 in combination with PDR001.
时间窗: 24 months
Incidence and severity of AEs and SAEs
Tolerability of DKY709 single agent treatment or DKY709 in combination with PDR001.
时间窗: 24 months
Incidence and severity of AEs and SAEs
次要结局
- Tmax of DKY709 and PDR001(24 months)
- Half-life of DKY709 and PDR001(24 months)
- AUC of DKY709 and PDR001(24 months)
- Progression Free Survival (PFS)(24 months)
- Cmax of DKY709 and PDR001(24 months)
- Best Overall Response (BOR)(24 months)
- Duration of Response (DOR)(24 months)
- Time to Progression (TTP)(24 months)
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (4)
Loading locations...
相似试验
已完成
1 期
A Study of DCLL9718S in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or DCLL9718S in Combination With Azacitidine in Participants With Previously Untreated AML Unsuitable for Intensive Induction ChemotherapyLeukemia, Myeloid, AcuteNCT03298516Genentech, Inc.19
招募中
1 期
A Phase 1 Study to Evaluate the Safety and Tolerability of TT-01488 in Patients With B-Cell MalignanciesB-Cell MalignanciesNCT05683717TransThera Sciences (Nanjing), Inc.37
进行中（未招募）
1 期
To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast CancerSolid TumorBreast CancerNCT03006172Genentech, Inc.200
终止
1 期
Study of ET140202 T Cells in Adults With Advanced Hepatocellular CarcinomaLiver NeoplasmHepatocellular CarcinomaMetastatic Liver CancerLiver CancerNCT03998033Eureka Therapeutics Inc.2
已完成
1 期
A Phase 1 Trial of NY-ESO-1 With GLA-SE in Patients With Unresectable or Metastatic CancerOvarian CancerMelanomaBreast CancerSarcomaNon-small Cell Lung CancerNCT02015416Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)13