A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Drug Combinations in Adult Patients With Advanced or Metastatic BRAF V600 Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 35
- 试验地点
- 5
- 主要终点
- Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
研究概览
简要总结
A phase Ib, open-label platform study of select drug combinations chosen in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies.
详细描述
This is a phase Ib, multi-center, open-label study with multiple treatment arms in adult patients with advanced or metastatic BRAF V600 (E, D, or K) in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies. The open platform design of this study is adaptive to allow removal of combination treatment arm(s) based on emerging data and facilitate introduction of new candidate combinations. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm.
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 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dabrafenib + LTT462 backbone arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Dabrafenib (Drug)
Dabrafenib + LTT462 backbone arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: LTT462 (Drug)
Dabrafenib + LTT462 + trametinib triplet arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Dabrafenib (Drug)
Dabrafenib + LTT462 + trametinib triplet arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: LTT462 (Drug)
Dabrafenib + LTT462 + trametinib triplet arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Trametinib (Drug)
Dabrafenib + LTT462 + LXH254 triplet arm 2
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
干预措施: Dabrafenib (Drug)
Dabrafenib + LTT462 + LXH254 triplet arm 2
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
干预措施: LTT462 (Drug)
Dabrafenib + LTT462 + LXH254 triplet arm 2
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
干预措施: LXH254 (Drug)
Dabrafenib + LTT462 + TNO155 triplet arm 3
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Dabrafenib (Drug)
Dabrafenib + LTT462 + TNO155 triplet arm 3
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: LTT462 (Drug)
Dabrafenib + LTT462 + TNO155 triplet arm 3
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: TNO155 (Drug)
Dabrafenib + LTT462 + spartalizumab triplet arm 4
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
干预措施: Dabrafenib (Drug)
Dabrafenib + LTT462 + spartalizumab triplet arm 4
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
干预措施: LTT462 (Drug)
Dabrafenib + LTT462 + spartalizumab triplet arm 4
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
干预措施: Spartalizumab (Biological)
Dabrafenib + trametinib + TNO155 triplet arm 5
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Dabrafenib (Drug)
Dabrafenib + trametinib + TNO155 triplet arm 5
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Trametinib (Drug)
Dabrafenib + trametinib + TNO155 triplet arm 5
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: TNO155 (Drug)
Dabrafenib + LTT462 + Tislelizumab triplet arm 6
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Dabrafenib (Drug)
Dabrafenib + LTT462 + Tislelizumab triplet arm 6
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: LTT462 (Drug)
Dabrafenib + LTT462 + Tislelizumab triplet arm 6
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
干预措施: Tislelizumab (Biological)
结局指标
主要结局
Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
时间窗: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
时间窗: 34 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Frequency of dose interruptions
时间窗: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Frequency of dose reductions
时间窗: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
Dose intensity
时间窗: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
次要结局
- AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments(30 months)
- Best overall response (BOR)(34 months)
- Progression free survival (PFS)(34 months)
- Overall response rate (ORR)(34 months)
- Duration of response (DOR)(34 months)
- Disease control rate (DCR)(34 months)
- Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)(30 months)
- AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments(30 months)
- Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments(30 months)
- Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments(30 months)
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG