A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of TNG260 as Single Agent and in Combination With an Anti-PD-1 Antibody In Patients With STK11 Mutated Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 126
- 试验地点
- 24
- 主要终点
- Measure antitumor activity using RECIST 1.1 (Phase 2 only)
研究概览
简要总结
The goal of this interventional clinical trial is to learn about TNG260, a CoREST inhibitor, in combination with pembrolizumab in patients with advanced solid tumors with a known STK11 mutation.
The main question[s] it aims to answer are:
- the recommended dose for Phase 2
- to evaluate the safety and tolerability of the combination therapy
- to determine the pharmacokinetics of TNG260
- to evaluate the initial antineoplastic activity
Participants will receive study treatment until they experience an undesirable side effect, their disease progresses or until they withdraw consent.
详细描述
This is a first-in-human Phase 1/2, open-label, multicenter, dose-escalation and expansion study designed to determine the maximum tolerated dose and recommended phase 2 dose(s) and evaluate the safety and tolerability, pharmacokinetics, and antineoplastic activity of escalating oral doses of TNG260 when administered with a standard dose of pembrolizumab in participants with locally advanced or metastatic STK11 mutated 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
- •Is ≥18 years of age at the time of signature of the main study ICF.
- •Has ECOG performance status of 0 or
- •Has measurable disease based on RECIST v1.
- •All participants must have documented STK11 mutation in a solid tumor, which is identified through a validated analytical method
- •Has confirmed histologic or cytologic diagnosis of a locally advanced or metastatic solid tumor.
- •Adequate organ function/reserve per local labs
- •Adequate liver function per local labs
- •Adequate renal function per local labs
- •Negative serum pregnancy test result at screening
- •Written informed consent must be obtained according to local guidelines
排除标准
- •Known allergies, hypersensitivity, or intolerance to TNG260, PD-1 antibody or its excipients
- •Uncontrolled intercurrent illness that will limit compliance with the study requirements
- •Active infection requiring systemic therapy
- •Currently participating in or has planned participation in a study of another investigational agent or device
- •Impairment of GI function or disease that may significantly alter the absorption of oral TNG260
- •Active prior or concurrent malignancy.
- •Central nervous system metastases associated with progressive neurological symptoms
- •Current active liver disease from any cause
- •Clinically relevant cardiovascular disease
- •A female patient who is pregnant or lactating
研究组 & 干预措施
Dose Escalation
Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD
干预措施: TNG260 (Drug)
Dose Escalation
Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD
干预措施: Pembrolizumab (Drug)
Dose Expansion in NSCLC with KRAS Wild type
Participants with STK11-mutant and KRAS-wild type NSCLC (squamous and non-squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab
干预措施: Pembrolizumab (Drug)
Dose Expansion in Advanced or Metastatic Solid Tumors
Participants with STK11-mutant solid tumors (including but not limited to pancreatic, endometrial, cervical, breast, and carcinoma of unknown primary) will receive TNG260 at the identified RP2D in combination with pembrolizumab
干预措施: Pembrolizumab (Drug)
Dose Expansion in NSCLC with KRAS Wild type
Participants with STK11-mutant and KRAS-wild type NSCLC (squamous and non-squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab
干预措施: TNG260 (Drug)
Dose Expansion in NSCLC with KRAS Mutation
Participants with STK11-mutant and KRAS-mutant NSCLC (squamous and non squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab
干预措施: TNG260 (Drug)
Dose Expansion in Advanced or Metastatic Solid Tumors
Participants with STK11-mutant solid tumors (including but not limited to pancreatic, endometrial, cervical, breast, and carcinoma of unknown primary) will receive TNG260 at the identified RP2D in combination with pembrolizumab
干预措施: TNG260 (Drug)
Dose Expansion in NSCLC with KRAS Mutation
Participants with STK11-mutant and KRAS-mutant NSCLC (squamous and non squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Measure antitumor activity using RECIST 1.1 (Phase 2 only)
时间窗: 12 weeks
To assess antineoplastic activity of TNG260 when administered in combination with pembrolizumab in participants with locally advanced unresectable or metastatic STK11-mutated solid tumors by measuring ORR, DOR, and PFS by RECIST 1.1
Determine the MTD and RP2D(s) (Phase 1 only)
时间窗: 42 days
To determine the MTD and RP2D(s) of TNG260 when administered in combination with pembrolizumab
次要结局
- Measure antitumor evidence of TNG260 + pembrolizumab antineoplastic activity by RECIST 1.1 (Phase 1 only)(12 weeks)
- Characterize Area Under the Curve (AUC) of TNG260(37 days)
- To measure changes in histone acetylation when administered with TNG260(12 weeks)
- Characterize the time to achieve Time to Maximal Concentration (Tmax) of TNG260(37 days)
- Characterize Terminal Half-life (T1/2) of TNG260(37 days)
- Characterize pembrolizumab concentrations when administered with TNG260(43 days)
- Safety and tolerability of TNG260 by CTCAE 5.0(42 days)
- Characterize Maximum Observed Plasma Concentration (Cmax) of TNG260(37 days)