A Phase 1/2 Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Patients With MET Overexpressing Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 11
- 主要终点
- Concentrations of cemiplimab when given in combination with REGN5093-M114
研究概览
简要总结
This study is researching an experimental drug called REGN5093-M114 by itself and in combination with cemiplimab. The study is focused on advanced non-small cell lung cancer (NSCLC) that produces too much of a protein called mesenchymal epithelial transition factor (MET) on the cancer cell surface. The aim of the study is to see how safe, tolerable, and effective the study drug is. This study will include 3 study groups, or cohorts, and each group is split into 2 parts:
Part 1: The main purpose of part 1 is to determine a safe dose of REGN5093-M114 (Cohorts A and B), and in combination with cemiplimab (Cohort C).
Part 2: The main purpose of part 2 is to use the REGN5093-M114 dose found for each cohort in part 1 to see how well the study drug works to shrink tumors.
The study is looking at several other research questions, including:
- What side effects may happen from receiving the study drug
- Does the study drug work to reduce or delay the progression of your cancer
- How much study drug is in the blood at different times
- Does the body make antibodies against the study drug (which could make the drug less effective or could lead to side effects)
详细描述
The trial was intended to be a Phase 1/2 trial, but no participants were enrolled in Phase 2
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 confirmed NSCLC that is at advanced stage for which there are no approved therapies available expected to confer clinical benefit as defined in the protocol
- •Willing to provide tumor tissue from newly obtained biopsy from tumor site. Newly obtained biopsies at tissue screening are required. An archival sample can be accepted only after discussion with the medical monitor and if the sample is not more than 6 months old and was obtained on the treatment regimen prior to study screening or after completion of the last therapy. The enrollment of patients will be based on an immunohistochemistry (IHC)-based assay using freshly obtained tumor biopsies or an archival biopsy as described above. Only patients with MET overexpressing tumors by central IHC analysis will be enrolled. For expansion cohorts only: tumor site for biopsy must not have been irradiated previously and must not be the only measurable lesion.
- •Tumor must overexpress MET protein as defined in the protocol
- •For expansion only: At least one lesion that is measurable by RECIST 1.
- •Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ and bone marrow function as defined in the protocol
排除标准
- •Has received treatment with an approved systemic therapy or has participated in any study of an investigational agent or investigational device within 2 weeks or 5 half-lives of the prior treatment, whichever is shorter with a minimum of 7 days from the first dose of study therapy
- •Has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities resulting from prior therapy except as described in the protocol
- •Has received radiation therapy or major surgery within 14 days of first administration of study drug or has not recovered from adverse events as defined in the protocol
- •Another malignancy that is progressing or requires active treatment except as noted in the protocol
- •Untreated or active primary brain tumor, central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
- •Encephalitis, meningitis, organic brain disease (eg Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study therapy
- •Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency as defined in the protocol
- •NOTE: Other protocol-defined Inclusion/ Exclusion criteria apply
研究组 & 干预措施
Phase 1. Dose Escalation
Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.
干预措施: REGN5093-M114 (Drug)
Phase 1. Dose Escalation
Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.
干预措施: Cemiplimab (Drug)
Phase 2. Dose Expansion
Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.
干预措施: REGN5093-M114 (Drug)
Phase 2. Dose Expansion
Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Concentrations of cemiplimab when given in combination with REGN5093-M114
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1) Cohort C
Treatment-emergent adverse events (TEAEs)
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
TEAEs leading to study treatment discontinuation
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
TEAEs leading to death
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE])
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
Concentrations of REGN5093-M114 in serum
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
Dose limiting toxicities (DLTs)
时间窗: Up to 28 days
Dose escalation (Phase 1)
Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
Serious adverse events (SAEs)
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
Concentrations of M24 in plasma
时间窗: Through study completion, an average of 2 years
Dose escalation (Phase 1)
Objective response rate (ORR)
时间窗: Through study completion, an average of 2 years
Dose expansion (Phase 2)
次要结局
- Laboratory abnormalities (grade 3 or higher per CTCAE)(Through study completion, an average of 2 years)
- Time to tumor response (TTR)(Through study completion, an average of 2 years)
- Overall survival (OS)(Through study completion, an average of 2 years)
- TEAEs leading to death(Through study completion, an average of 2 years)
- ORR(Through study completion, an average of 2 years)
- TEAEs leading to study treatment discontinuation(Through study completion, an average of 2 years)
- SAEs(Through study completion, an average of 2 years)
- Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum(Through study completion, an average of 2 years)
- Incidence of ADA to REGN5093-M114 over time in monotherapy(Through study completion, an average of 2 years)
- Titer of ADA to REGN5093-M114 over time in monotherapy(Through study completion, an average of 2 years)
- Incidence of ADA to REGN5093-M114 over time in combination with cemiplimab(Through study completion, an average of 2 years)
- TEAEs(Through study completion, an average of 2 years)
- Concentrations of REGN5093-M114 in serum(Through study completion, an average of 2 years)
- Concentrations of M24 in plasma(Through study completion, an average of 2 years)
- Concentrations of cemiplimab when given in combination with REGN5093-M114(Through study completion, an average of 2 years)
- Incidence of Anti-drug antibodies (ADA) against cemiplimab over time, when given in combination with REGN5093-M114(Through study completion, an average of 2 years)
- Titer of ADA against cemiplimab over time, when given in combination with REGN5093-M114(Through study completion, an average of 2 years)
- Progression free survival (PFS)(Through study completion, an average of 2 years)
- Duration of response (DOR)(Through study completion, an average of 2 years)
- Disease control rate (DCR)(Through study completion, an average of 2 years)
- Titer of ADA to REGN5093-M114 over time in combination with cemiplimab(Through study completion, an average of 2 years)