A Phase 1/1b Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of KIN-2787 in Participants With BRAF and/or NRAS Mutation-positive Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 127
- 主要终点
- Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-2787 in adults with BRAF/NRAS-mutated advanced or metastatic solid tumors.
详细描述
This is a two-part, open-label, multi-center, dose escalation and dose expansion study in participants with BRAF mutation-positive and/or NRAS mutation-positive tumors designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of KIN-2787, a RAF small molecule kinase inhibitor, to determine a recommended Phase 2 dose (RP2D) of KIN-2787, and to assess the objective response to KIN-2787 therapy alone and in combination with binimetinib, a mitogen-activated protein kinase (MEK) inhibitor.
The dose expansion phase (Part B) will assess the safety and efficacy of KIN-2787 at the recommended dose and schedule in patients with cancers that contain BRAF Class I, II or III mutations, including lung cancer, melanoma, and other selected solid tumors.
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
- •Provide written informed consent prior to initiation of any study-specific procedures.
- •Metastatic or advanced stage solid tumor
- •Known BRAF Class I, Class II, or Class III alteration or melanoma with an NRAS mutation as confirmed by previous genomic analysis of tumor tissue or ctDNA.
- •Measurable (Part A and B) or evaluable (Part A only) disease by RECIST v1.
- •ECOG performance status 0-1
- •Adequate organ function, as measured by laboratory values (criteria listed in protocol).
- •Able to swallow, retain, and absorb oral medications.
排除标准
- •Known participants who have received local therapy with either surgery and/or radiation therapy (participants with asymptomatic untreated brain metastasis may be eligible if met with certain criteria)
- •In Part B Dose Expansion, previous treatment with any approved or in-development small molecule BRAF-, MEK-, or MAPK-directed inhibitor therapy.
- •GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease.
- •Active, uncontrolled bacterial, fungal, or viral infection.
- •Participant with a positive test result for SARS-CoV2 infection, is known to have asymptomatic infection or is suspected of having SARS-CoV2, is excluded
- •Women who are lactating or breastfeeding, or pregnant.
- •Participants with any other active treated malignancy within 3 years prior to enrollment
- •Complete inclusion and exclusion criteria are listed in the clinical study protocol.
研究组 & 干预措施
Dose Escalation Monotherapy (Part A1)
Dose escalation of KIN-2787
干预措施: KIN-2787 (Drug)
Dose Expansion Monotherapy (Part B1)
Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787
干预措施: KIN-2787 (Drug)
Dose Escalation Combination therapy (Part A2)
Dose escalation of KIN-2787 and binimetinib
干预措施: KIN-2787 and binimetinib (Drug)
Dose Escalation Combination therapy (Part B2)
Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib
干预措施: KIN-2787 and binimetinib (Drug)
结局指标
主要结局
Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination
时间窗: Initiation of study drug through 28 days after last dose (up to approximately 18 months)
To determine the safety and tolerability of oral administration of KIN-2787 + binimetinib including DLTs, and to identify the MTD and/or the appropriate dose for further clinical investigation.
In Part B (Dose Expansion) - duration of overall response (DOR).
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression
Part A1 Dose escalation monotherapy:
时间窗: Initiation of study drug through 28 days after last dose (up to approximately 18 months)
To determine the safety and tolerability of oral administration of KIN-2787 including dose-limiting toxicities (DLTs), and to identify the maximum tolerated dose (MTD) and/or the appropriate dose for further clinical investigation in Part B Dose Expansion.
In Part B (Dose Expansion) - duration of stable disease.
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
In Part B (Dose Expansion) - disease control rate (DCR).
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
In Part B (Dose Expansion) - objective response rate (ORR) using RECIST v1.1.
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
To assess preliminary evidence of the anti-cancer activity of KIN-2787 and for (B2) KIN-2787 + binimetinib
次要结局
- Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to Cmax.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to AUC.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to AUC.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to tmax.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to tmax.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to Cmax.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to AUC.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))
- Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to Cmax.(Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months))