PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer: a Phase II Trial (PFROST)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 20
- 试验地点
- 20
- 主要终点
- Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
研究概览
简要总结
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Disease assessment will be performed every 8 weeks according to RECIST criteria.
详细描述
PF-06463922 is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration. The results showed that PF-06463922 is most potent against ROS1 and ALK, with selectivity ratios >100-fold for ROS1 over the 204 kinases tested. A recent study has investigated the activity of PF-06463922 against the crizotinib-resistant ROS1G2032R mutation in both recombinant enzyme and cell-based assays. PF-06463922 effectively inhibited the catalytic activity of recombinant ROS1G2032R and the CD74-ROS1G2032R fusion kinase in BaF3 cells. This effect translated directly into an antiproliferative response. These results, together with its exquisite ROS1 potency and ability to suppress the resistant ROS1 mutations, supports the clinical evaluation of PF-06463922 in ROS1-positive NSCLC, including patients who have developed resistance to crizotinib because of the acquired G2032R mutation and/or brain metastases.
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Disease assessment will be performed every 8 weeks according to RECIST criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Written informed consent;
- •Male or female patient ages ≥ 18 years;
- •Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1 rearrangement;
- •Possibility to perform a new tumor biopsy or tumor tissue collected at the time or after crizotinib failure;
- •Patient pretreated with crizotinib with evidence of disease progression during crizotinib therapy;
- •At least one radiological measurable disease according to RECIST criteria;
- •At least 1 previous standard chemotherapy regimen;
- •Performance status 0-2 (ECOG);
- •Patient compliance to trial procedures
- •Adequate bone marrow function (ANC ≥ 1.5x109/L, platelets ≥ 100x109/L, haemoglobin > 9 g/dl);
- •Adequate liver function (bilirubin < grade 2, transaminases no more than 3xULN/<5xULN in present of liver metastases);
- •Normal level of alkaline phosphatase and creatinine;
- •If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [intrauterine contraceptive device (IUD), birth control pills, or barrier device] during and for ninety (90) days after end of treatment.
排除标准
- •No ROS1 rearrangement
- •No previous therapy with crizotinib;
- •No evidence of crizotinib failure;
- •No post-crizotinib tumor tissue available;
- •Absence of any measurable lesions;
- •No previous chemotherapy;
- •Concomitant radiotherapy or chemotherapy;
- •Symptomatic brain metastases;
- •Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin;
- •Predisposing factors for acute pancreatitis (e.g., uncontrolled hyperglycaemia, current gallstone disease, alcoholism);
- •History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis);
- •Pregnancy or lactating female;
- •Other serious illness or medical condition potentially interfering with the study.
研究组 & 干预措施
Lorlatinb Arm
Eligible patients will be treated with Lorlatinib at the dose of 100 mg QD p.o.
干预措施: Lorlatinib (Drug)
结局指标
主要结局
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
时间窗: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
次要结局
- Progression-free survival (PFS), The length of time during and after the treatment of a disease,that a patient lives with the disease but it doesn't get worse.(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months)
- Overall Survival (OS): Time from the start of treatment until death from any cause(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months)
- Correlation with additional tumor biomarkers in tumor tissue or blood(From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months)