A Phase 1 Open-label, Dose-escalation and Cohort Expansion Study of LUNA18 Monotherapy and Combination Therapy in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 128
- 试验地点
- 20
- 主要终点
- Safety and tolerability of LUNA18 (Dose-limiting toxicities) when administered as a single agent [Part A] and in combination with other anti-cancer drugs [Part D]
研究概览
简要总结
This is a Phase 1 dose-escalation and cohort expansion study that will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of LUNA18 when administered as a single agent or in combination with other anti-cancer drugs in patients with locally advanced or metastatic solid tumors.
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
- •Age >= 18 years at time of signing informed consent form
- •ECOG performance status of 0 or 1
- •Patients with a histologically or cytologically proven diagnosis of a locally advanced, recurrent, or metastatic incurable solid tumor for which standard therapy either does not exist or has proven ineffective or intolerable
- •Patients with documented RAS alterations positive solid tumors
- •Patients with measurable disease per RECIST v1.1
排除标准
- •Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), unstable angina, or myocardial infarction within the previous 6 months or unstable arrhythmias within the previous 3 months
- •Patients with primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases
- •Patients with current severe, uncontrolled systemic disease (including, but not limited to, clinically significant cardiovascular disease, pulmonary disease, or renal disease, ongoing or active infection)
- •Patients with a history or complication of interstitial lung disease (ILD)
研究组 & 干预措施
Dose escalation part (Part A)
Patients will receive LUNA18 capsule(s) at escalated doses
干预措施: LUNA18 (Drug)
Biomarker part (Part B)
Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A
干预措施: LUNA18 (Drug)
Cohort expansion part (Part C)
Patients will receive LUNA18 capsule(s) at the recommended dose
干预措施: LUNA18 (Drug)
Backfill part (Part AA)
Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A
干预措施: LUNA18 (Drug)
Dose finding part (Part D)
Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses
干预措施: LUNA18 (Drug)
Dose finding part (Part D)
Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses
干预措施: Cetuximab (Drug)
Cohort expansion part (Part E)
Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose
干预措施: LUNA18 (Drug)
Cohort expansion part (Part E)
Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose
干预措施: Cetuximab (Drug)
结局指标
主要结局
Safety and tolerability of LUNA18 (Dose-limiting toxicities) when administered as a single agent [Part A] and in combination with other anti-cancer drugs [Part D]
时间窗: From Cycle 0 Day 1 until Cycle 1 Day 28 (Cycle 0 is 6-9 days, and Cycle 1 is 28 days)
Incidence and nature of dose-limiting toxicities (DLTs)
Safety and tolerability of LUNA18 (Adverse Events) [Part A, AA, B, C, D and E]
时间窗: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Incidence, nature and severity of adverse events, with severity determined per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
Plasma concentrations of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D]
时间窗: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Plasma concentrations of LUNA18
Maximum plasma concentration (Cmax) of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D]
时间窗: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Maximum plasma concentration (Cmax) of LUNA18
Time to reach maximum plasma drug concentration (Tmax) of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D]
时间窗: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Time to reach maximum plasma drug concentration (Tmax) of LUNA18
Area under the concentration versus time curve (AUC) of LUNA18 when administered as a single agent [Part A, AA] and in combination with other anti-cancer drugs [Part D]
时间窗: From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months)
Area under the concentration versus time curve (AUC) of LUNA18
Phosphorylation level of ERK protein (pERK) in tumor tissues [Part B]
时间窗: From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible
Phosphorylation level of ERK protein (pERK) in tumor tissues biomarkers as applicable in tumor tissues
Preliminary anti-tumor activity of LUNA18 when administered as a single agent [Part B, C] and in combination with other anti-cancer drugs [Part E]
时间窗: From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months)
Objective response, defined as a confirmed complete response (CR) or partial response (PR) as best overall response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
次要结局
- Preliminary anti-tumor activity of LUNA18 [Part A, AA, B, C, D and E](From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months))
- Plasma concentrations of LUNA18 [Part B, C and E](From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months))
- Phosphorylation level of ERK protein (pERK) in tumor tissues [Part A, AA, C, D, E](From screening until the time of clinical responses and/or the time of progressive disease (up to approximately 43 months), if feasible)
- Preliminary anti-tumor activity of LUNA18 when administered as a single agent [Part A, Part AA] and in combination with other anti-cancer drugs [Part D](From screening until disease progression, study discontinuation, withdrawal or death, whichever occurs first (up to approximately 43 months))
- Anti-drug antibody to LUNA18[Part A, AA, B, C, D and E](From Cycle 0 Day 1 (Cycle 0 is 6-9 days) until study completion or treatment discontinuation (up to approximately 43 months))