NCT03219268已完成1 期
A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, A Bispecific DART® Protein Binding PD-1 and LAG-3 in Patients With Unresectable or Metastatic Neoplasms
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 277
- 试验地点
- 78
- 主要终点
- Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy)
研究概览
简要总结
The primary goal of this Phase 1 study is to characterize the safety and tolerability of tebotelimab and establish the maximum tolerated dose (MTD) of tebotelimab in advanced solid tumors, and tebotelimab in combination with margetuximab in HER2+ advanced solid tumors. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of tebotelimab will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically proven, locally advanced unresectable or metastatic solid tumors (or hematologic malignancies, Cohort Expansion only) for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy ≥ 12 weeks
- •Measurable disease
- •Tissue specimen available for retrospective analysis of PD-1, PD-L1, LAG-3, and MHC-II expression
- •Acceptable laboratory parameters
- •HER2+ Cohort:
- •Locally advanced or metastatic HER2+ locally advanced or metastatic solid tumors, regardless of organ of origin.
- •i. The cancer must have progressed following standard therapy, or has progressed during or after HER2-directed therapy if approved and available for patients with HER2+ breast, gastric, or gastroesophageal junction cancer.
- •ii. History of HER2 positivity defined as 3+ by IHC or 2+ by Immunohistochemistry (IHC) in combination with in situ hybridization (ISH) positivity most recent tumor biopsy.
- •All patients in the HER2+ cohort must be willing to provide consent for a baseline and on-treatment tumor biopsy during the screening period and within 14 days prior to Cycle 3 Day
- •Exceptions may be made based on a medical contraindication at the discretion of the Sponsor's Medical Monitor. This requirement will be discontinued after an adequate number of samples are collected, as determined by the Sponsor.
排除标准
- •Symptomatic central nervous system (CNS) metastases or primary CNS lymphoma
- •History of allogeneic bone marrow, stem-cell, or solid organ transplant
- •History of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
- •Treatment with any systemic chemotherapy within 3 weeks prior to the initiation of study drug; treatment with biologics or investigational therapy within the 4 weeks prior to the initiation of study drug.
- •Major surgery within 4 weeks prior to the initiation of study drug.
- •Prior treatment with combination of monoclonal antibodies against PD-1 and LAG-3 (Cohort Expansion only).
- •Treatment with radiation therapy within 2 weeks prior to the initiation of study drug.
- •Clinically significant cardiovascular disease.
- •QTcF prolongation > 480 milliseconds
- •HER2+ cohort: left ventricular ejection fraction less than 50%
- •Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
- •Active pneumonitis or history of non-infectious pneumonitis.
- •Clinically significant gastrointestinal disorders.
- •Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.
- •Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
- •Known history of hepatitis B (except in hepatocellular carcinoma) or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR)
- •Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed
- •Dementia or altered mental status that would preclude understanding and rendering of informed consent
- •Confirmed or presumed COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines/standards. Patients with a positive test result for SARS-CoV-2 infection, known asymptomatic infection, or presumed infection are excluded. Patients may be considered eligible after a resolved SARS-CoV-2 infection once he or she remains afebrile for at least 72 hours and after other SARS-CoV-2-related symptoms have fully recovered to baseline for a minimum of 72 hours.
结局指标
主要结局
Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy)
时间窗: up to 24 months
Safety Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)
时间窗: up to 24 months
Safety
次要结局
- Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab(At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years)
- Total body clearance of the drug from plasma (CL) of tebotelimab(Cycle 1 Day 1 out to Cycle 1 Day 15)
- Terminal half-life (t1/2) of tebotelimab(Cycle 1 Day 1 out to Cycle 1 Day 15)
- Median Duration of response (DoR)(Throughout the study, up to 4 years.)
- Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab(From Day 1 to Day 15 after the first and second doses)
- Apparent volume of distribution at steady state (Vss) of tebotelimab(Cycle 1 Day 1 out to Cycle 1 Day 15)
- Number of patients with anti-drug antibody(Study Day 1, 15, 29, 57, 85, 113, then every 56 days up to 2 years Tebotelimab plus margetuximab: Day 1, 22, 43, and then every 6 weeks until treatment discontinuation)
- Objective response rate (ORR)(Throughout the study, up to 4 years.)
- Trough plasma concentration (Ctrough) of tebotelimab(Study Days 1, 15, 29, 43 in Cycles 1 and 2 and Day 1 of each subsequent cycle s until treatment discontinuation, up to 2 years)
- Progression-free survival (PFS)(Throughout the study, up to 4 years.)
- Median Overall survival (OS)(Throughout the study, up to 4 years.)
- Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab(At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years)
研究者
研究点 (78)
Loading locations...
相似试验
招募中
1 期
A Study of MGC028 in Participants With Advanced Solid TumorsCholangiocarcinomaNCT06723236MacroGenics124
终止
1 期
A Phase I Study of JS108 in Patients With Advanced Solid TumorsAdvanced Solid TumorsNCT04601285Shanghai Junshi Bioscience Co., Ltd.25
已完成
早期 1 期
A First-time-in-human Study of BGB149Healthy VolunteersNCT03795142BerGenBio ASA24
终止
1 期
A Trial to Find Safe and Active Doses for an Investigational Drug, CX-904, for Patients With Advanced Solid TumorsSolid TumorsNCT05387265CytomX Therapeutics83
已完成
1 期
GEN-001 (Live Biotherapeutic Product) and Avelumab Combination Study for Patients With Solid Tumors Who Have Progressed on Anti-PD-(L)1 TherapySolid TumorNon Small Cell Lung CancerSquamous Cell Carcinoma of Head and NeckUrothelial CarcinomaNCT04601402Genome & Company11