Phase 1/2 Open Label Study Of Pf 06459988 (Epidermal Growth Factor Receptor T790m Inhibitor) In Patients With Advanced Epidermal Growth Factor Receptor Mutant (Del 19 Or L858r + - T790m) Non Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Pfizer
- 主要终点
- Number of Participants With Objective Response (phase 2)
研究概览
简要总结
Phase 1 - open label, multi-center, non-randomized, safety, pharmacokinetic and pharmacodynamics dose escalation study of PF-06459988 as a single agent in patients with advance EGFRm NSCLC (del 19, L858R, +/- T790M). The resulting PF-06459988 dose selected from the phase 1 portion will undergo a series of sub-studies to fully characterize the impact of food, antacid and CYP3A4 inhibitors/inducers. The PK studies are in addition to the MTD expansion and will be completed prior to the initiation of Phase 2. Phase 2 is an open label, multi-center single-arm study of PF-06459988 for the assessment of antitumor activity in patients with advanced EGFRm (del 19 or L858R) NSCLC with T790M.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- •Evidence of histological or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del19 or L858R) NSCLC that is resistant to standard therapy. Patients must have progressed on treatment with an EGFR TKI, and may have also received other line of therapy.
- •Tissue available (formalin fixed paraffin embedded (FFPE) block or 10 unstained sections (5 micron)
- •Patients must be willing to participate in additional PK studies as required (cohort dependent); patients will be informed of which PK studies are required prior to consenting for study participation
- •Adequate Bone Marrow Function (Complete Blood Count laboratory test results)
- •Adequate Liver Function (Laboratory test)
排除标准
- •Previously diagnosed brain metastases, unless the patient has completed their treatment and has recovered from the acute effects of radiation therapy or surgery prior to the study registration, have discontinued corticosteroid treatment for these metastases for at least 2 weeks and are neurologically stable
- •Systemic anti-cancer therapy within 4 weeks of starting study treatment excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent for a minimum of 5 days prior to starting study drug
- •Hypertension that cannot be controlled by medication (150/100 mmHg despite optimal medical therapy).
研究组 & 干预措施
Single agent - study drug
The study will evaluate single-agent PF-06459988
干预措施: PF-06459988 (Drug)
结局指标
主要结局
Number of Participants With Objective Response (phase 2)
时间窗: Time from first dose of study drug to objective response of CR or PR up to 24 months
Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those as noted in the RECIST Criteria: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions
Number of participants with Dose-limiting toxicities (DLT) (phase 1)
时间窗: up to 21 days
The target probability of DLT at MTD will be 30%
次要结局
- Number of Participants With Objective Response for those patients with measurable disease (phase 1)(time from first dose of study drug until objective response of CR or PR up to 24 months)
- Progression-Free Survival (PFS) - Phase 2(time from first dose of study drug until Disease Progression or death (whichever first) up to 24 months)