NCT04111458进行中（未招募）1 期
A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With Trametinib in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 71
- 试验地点
- 13
- 主要终点
- Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a study in adults with advanced cancer (solid tumours) in whom previous chemotherapy was not successful. Only people who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster.
The study tests 2 medicines called BI 1701963 and trametinib. BI 1701963 prevents reactivation of KRAS. In this study, BI 1701963 is given to humans for the first time. Trametinib is an approved medicine (MEK inhibitor).
The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with trametinib the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with trametinib is able to make tumours shrink.
Participants can stay in the study as long as they benefit from treatment and can tolerate it.
During this time, they get tablets of BI 1701963 and trametinib once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.
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
- •Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in tumour tissue or blood prior to screening
- •At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function
- •Age ≥18 years of age, or over the legal age of consent as required by local legislation.
- •Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial.
- •Women of childbearing potential who are not surgically sterilized must have a negative serum pregnancy test completed during the Screening period
- •Further inclusion criteria apply
- •Monotherapy and combination therapy dose escalation and monotherapy dose confirmation part
- •- Documented disease progression despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage
- •Combination dose confirmation and expansion cohort
- •Pathologically confirmed diagnosis of adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
- •Locally advanced stage IIIb or metastatic stage IV Non-small cell lung cancer (NSCLC)
- •Patients must have received both chemotherapy and immunotherapy
排除标准
- •Previous anticancer chemotherapy within 3 weeks of the first administration of trial drug.
- •Previous treatment with RAS, Mitogen-activated protein kinase (MAPK) or Son of sevenless 1 (SOS1) targeting agents
- •Major surgery performed within 4 weeks prior to start of treatment
- •Uncontrolled hypertension, congestive heart failure NYHA classification of ≥3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to start of treatment
- •Left ventricular ejection fraction (LVEF) <50 %
- •Congenital long QT prolongation syndrome
- •Mean resting corrected QT interval (QTcF) >470 msec
- •Leptomeningeal carcinomatosis
- •Presence or history of uncontrolled or symptomatic brain metastases
- •Known pre-existing interstitial lung disease
- •Known active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B Deoxyribonucleic acid (DNA)), active hepatitis C infection (defined as presence of Hep C Ribonucleic acid (RNA))
- •Active infectious disease
- •Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug
- •History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED)
- •Further exclusion criteria apply
- •Combination part
- •- Hypersensitivity to any of the excipients listed in the current Summary of Product Characteristics (SmPC)/Package insert (PI) of trametinib
研究组 & 干预措施
BI 1701963 + Trametinib
Experimental
干预措施: BI 1701963 (Drug)
BI 1701963 monotherapy
Experimental
干预措施: BI 1701963 (Drug)
BI 1701963 + Trametinib
Experimental
干预措施: Trametinib (Drug)
结局指标
主要结局
Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs)
时间窗: 4 weeks
Dose confirmation (Part B) - Number of patients with DLTs during the on-treatment period
时间窗: Up to 3 years
Dose confirmation (Part B) and expansion (Part C) - Objective response
时间窗: Up to 3 years
次要结局
- Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)(Up to 5 weeks)
- Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)(Up to 5 weeks)
- Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: Cmax (maximum measured concentration of the analyte in plasma)(Up to 5 weeks)
- Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)(Up to 5 weeks)
- Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)(Up to 5 weeks)
- Dose confirmation (Part B) and expansion (Part C) - Progression-free survival(6 months)
- Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)(Up to 5 weeks)
- Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma)(Up to 5 weeks)
- Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)(Up to 5 weeks)
- Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR)(Up to 3 years)
- Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres)(Up to 3 years)
- Dose confirmation (Part B) and expansion (Part C) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period(Up to 3 years)
- Dose confirmation (Part B) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period(Up to 3 years)
研究者
研究点 (13)
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