A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 40
- 试验地点
- 11
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLT) (Part 1)
研究概览
简要总结
To assess the safety and tolerability at increasing dose levels of PF-06650808 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
研究设计
- 研究类型
- Interventional
- 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
- •Diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available
- •Previously treated metastatic triple negative breast cancer that expresses Notch3 with at least one measurable lesion
- •Adequate bone marrow, renal and liver function
排除标准
- •Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of starting study treatment
- •Patients with known symptomatic brain metastases requiring steroids
- •Prior treatment with a compound of the same mechanism
研究组 & 干预措施
PF-06650808
干预措施: PF-06650808 (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLT) (Part 1)
时间窗: Day 1 up to Day 21
Severity of AEs (adverse events ) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the purpose of dose escalation, any of the following AEs which were not considered related to disease progression occurring in the first cycle of treatment (21 days) were classified as DLTs: 1) Hematologic: Grade 4 neutropenia lasting \>7 days; Febrile neutropenia; Grade\>=3 neutropenia with infection; Any grade thrombocytopenia associated with clinically significant or life threatening bleeding; Grade 4 thrombocytopenia \>=72 hours or platelets\<=10,000/mm3 regardless of duration. 2) Non hematologic: Grade\>=3 toxicities except those that had not been maximally treated; Delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression. 3) clinically important or persistent toxicities may have been considered a DLT following review by the Sponsor and the investigators.
Percentage of Participants With Objective Response (Part 1 and Part 2)
时间窗: Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 3 years
Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant achieved complete response (CR) if both target and non-target lesions achieved CR, no new lesions; achieved partial response (PR) if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits. The overall objective response was defined as confirmed CR and PR.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 1 and Part 2)(3 years)
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Chemistries) (Part 1 and Part 2)(3 years)
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Urinalysis) (Part 1 and Part 2)(3 years)
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Hematology) (Part 1 and Part 2)(3 years)
- Number of Participants With Vital Signs Meeting Categorical Summarization Criteria (Part 1 and Part 2)(3 years)
- Maximum Observed Serum Concentration (Cmax) (Part 1 and Part 2)(Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4)
- Time to Reach Maximum Observed Serum Concentration (Tmax) (Part 1 and Part 2)(Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4)
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) (Part 1 and Part 2)(Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4)
- Clearance (CL) (Part 1 and Part 2)(Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1)
- Volume of Distribution at Steady State (Vss) (Part 1 and Part 2)(Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1)
- Terminal Elimination Half-Life (t1/2) (Part 1 and Part 2)(Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4)
- Number of Participants With the Presence of Anti-PF-06650808 Antibodies (Part 1 and Part 2)(3 years)
- Progression Free Survival and Overall Survival (Part 2)(3 years)