A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, -Radiation Dosimetry, and Preliminary Anti-Neoplastic Activity of LNTH-2403, a LRRC15-targeted 177Lutetium-labeled Monoclonal Antibody, in Participants With Relapsed / Refractory Osteosarcoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 2
- 主要终点
- To identify the maximum tolerated dose (MTD) of LNTH-2403 in participants with R/R osteosarcoma (Ph1)
研究概览
简要总结
This is a multi-center, non-randomized, open-label, dosimetry and dose-escalation, cohort-expansion study of LNTH-2403 administered to subjects with relapsed / refractory (R/R) osteosarcoma. This study consists of 2 phases: (1) a dosimetry and dose escalation phase; and (2) a cohort expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all the following criteria to be enrolled in the study
- •Histopathologic documented diagnosis of R/R osteosarcoma
- •Must have disease characterized by at least one of the following (Participants meeting only (b.), only (c.), or only (b. and c.) must be discussed with and receive written approval from the Sponsor to qualify).
- •Measurable as defined in RECIST 1.1
- •Evaluable non-measurable disease as per RECIST 1.1
- •Bone only without a soft tissue component: must be 18F-FDG-PET avid and evaluable by serial 18F-FDG-PET imaging studies.
- •Age: a. First Cohort in Phase 1: ≥ 18 years-of-age at the time of signature of the main study ICF. b. Second and subsequent cohorts, in Phase 1 and all participants in Phase 2: ≥12years-of-age at the time of signature of the main ICF.
- •Performance Status:
- •Eastern Cooperative Oncology Group (ECOG) Performance Score (PS): 0 - 2
- •Lansky PS ≥
- •Body weight: ≥ 30 kg.
- •Tumor biopsies; Fresh or Archival
- •Progression following at least one course of chemotherapy, which includes neoadjuvant / perioperative systemic therapy.
- •All adverse events (AEs) related to prior therapies (chemotherapy / systemic therapies, radiation, surgery) must have resolved to Grade 1 or baseline
- •Organ Function
- •Pregnancy Women of Child-Bearing Potential (WOCBP) must have a negative serum pregnancy test result at screening
- •Contraception- Male participants with a WOCBP partner must use 2 forms of acceptable contraception
- •Written informed consent and/or assent must be obtained according to local guidelines and signed and dated by the participant, parent, and/or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
排除标准
- •Participants meeting any of the following criteria will be excluded from the study
- •Known allergies, hypersensitivity, or intolerance to LNTH-2403 and/or its excipients
- •Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, may affect the participant's safety, compliance with the study, or otherwise impair the assessment of study results
- •Concurrent treatment with any other anti-neoplastic agents, including localized radiation therapy
- •Known active infection
- •Participation in an interventional study of another investigational agent
- •Prior therapies or diagnostics
- •Active prior or concurrent malignancy: immunoglobulin),
- •Known active liver disease from any cause, Hepatitis A Virus
- •Known to be human immunodeficiency virus (HIV) positive
- •Clinically relevant cardiovascular disease
- •Receipt of live vaccine within the 30 days prior to the first dose o
- •A female participant who is pregnant or breastfeeding
- •Major surgical procedure within 28 days of the first dose of LNTH-
- •Participant is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions
研究组 & 干预措施
Phase 1- Escalating doses of LNTH-2403 administered once every 8 weeks
Phase 1 will evaluate escalating doses of LNTH-2403 administered once every 8 weeks, with the potential to explore other dosing schedules based on observed radiation dosimetry and PK parameters and safety and tolerability data.
干预措施: LNTH2403 Phase 1 dose (Drug)
Phase 2 will evaluate LNTH-2403 as a single agent at the recommended phase 2 dose
Phase 2 will evaluate LNTH-2403 as a single agent in participants with R/R osteosarcoma at the recommended phase 2 dose (RP2D).
干预措施: Phase 2; LNTH2403 a single agent recommended phase 2 dose (RP2D). (Drug)
结局指标
主要结局
To identify the maximum tolerated dose (MTD) of LNTH-2403 in participants with R/R osteosarcoma (Ph1)
时间窗: From enrollment to the end of treatment at 8 weeks
Incidence of DLTs during the first 8 weeks (DLT evaluation window) after the first dose of LNTH-2403
To evaluate the safety and tolerability profile of LNTH-2403 in participants with R/R osteosarcoma (Ph1)
时间窗: From enrollment to the end of treatment at 8 weeks
Type, frequency, severity, timing, and relationship to LNTH-2403 of all Treatment-emergent adverse event, (TEAEs) and Serious adverse events, (SAEs)
To assess the preliminary anti-neoplastic activity of LNTH-2403 in participants with R/R osteosarcoma (Ph2)
时间窗: From enrollment to Event-Free Survival (EFS) at 4 months
Event-Free Survival (EFS) at 4 months
次要结局
- To assess the preliminary anti-neoplastic activity of LNTH-2403 in participants with R/R osteosarcoma (Ph1)(8 weeks)
- To describe the safety and tolerability profile of LNTH-2403 in participants with R/R osteosarcoma (Ph2)(4 months)