Phase I/Ib Trial of Single Agent PBF-999 in Solid Tumour Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
研究概览
简要总结
Multicentric phase I (dose escalation plus expansion) clinical trial of PBF-999 in patients with immunotherapy naïve and pretreated solid tumors to evaluate the safety, tolerability and preliminary efficacy of the compound
详细描述
The phase I dose escalations will be conducted utilizing the standard 3+3 dose escalation method. Pharmacokinetic (PK) data will be obtained for PBF-999.
The phase I dose expansion will consist of 1 group including immunotherapy naïve and pretreated (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations) solid tumors cancer patients. Pharmacodynamic (PD) data will be obtained for potential biomarker analysis with pre-treatment and on-treatment tumor biopsies.
Phase I Dose Escalation (3+3 Design):
- The MTD will be defined as the highest dose level at which less than 2 out of 6 patients (<33%) experience DLT in Cycle 1 (first 28 days).
Phase I Safety Expansion Once RP2D has been declared for PBF-999 using the standard 3+3 design, up to 20 additional solid tumor cancer patients may be treated at the RP2D to further explore safety and tolerability of the selected PBF-999 dose.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced/metastatic histologically confirmed solid tumor
- •At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- •Patients who has progressed to the standard therapy
- •ECOG performance status of 0/1
- •Age greater than 18 years.
- •Adequate bone marrow, renal and hepatic function
- •Able and willing to give valid written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol (immune)therapy (not mandatory but highly recommended).
- •Prior immunotherapy is allowed
排除标准
- •Participation in another clinical study with an investigational product during the last 4 weeks or 5 half-lifes prior to starting on treatment.
- •Symptomatic and/or untreated Brain Metastases
- •Pregnancy or breast feeding
- •Serious uncontrolled medical disorder or active infection that in the investigator's opinion would impair the patient's ability to receive study treatment.
- •Concurrent use of other anticancer approved or investigational agents is not allowed.
- •Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- •Prior malignancy in past 2 years or as identified in Section 7.2 of this protocol
- •Patients receiving systemic steroids ≥ 10mg/day of prednisone or the equivalent
- •Concurrent administration of strong inhibitors or moderate inducers of CYP1A2 is not permitted; administration must be discontinued at least 7 days prior to initiating study drug administration.
研究组 & 干预措施
PBF-999 20 mg
干预措施: PBF-999 (Drug)
PBF-999 40 mg
干预措施: PBF-999 (Drug)
PBF-999 80 mg
干预措施: PBF-999 (Drug)
PBF-999 120 mg
干预措施: PBF-999 (Drug)
recommended phase 2 dose (RP2D)
干预措施: PBF-999 (Drug)
结局指标
主要结局
Number of Adverse Events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
时间窗: 28 Days
AEs will be described by system organ class and preferred tem using the Medical Dictionary for Regulatory Activities (MedDRA). Clinically relevant Laboratory abnormalities with toxicity grades according to the NCI CTCAE v4.03 will be derived and summarized.
The Maximun Tolerated Dose (MTD) of PBF-999
时间窗: 28 Days
The MTD evaluation will be based on the Dose-limiting Toxicity (DLT) of the treated Population and will include Adverse events (AEs), Serious Adverse events (SAEs) and laboratory evaluations. DLT Evaluable Population will be all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with PBF-999 and complete the safety follow-up through the DLT evaluation period or experience a DLT during the DLT evaluation period.
次要结局
- Efficacy of PBF-999 as measured by progression-free survival (PFS)(2 years)
- Efficacy of PBF-999 as measured by overall survival (OS)(2 years)
- PBF-999 peak concentration in plasma "Cmax"(Day 1, Day 8 and Day 29)
- Efficacy of PBF-999 treatment as measured by Objective response rate (ORR(2 years)
- Efficacy of PBF-999 as measured by duration of response (DoR)(2 years)
- Time to PBF-999 peak concentration in plasma "Tmax(Day 1, Day 8 and Day 29)
- The area under PBF-999 plasma concentration-time curve to infinite time "AUC(0-inf)(Day 1, Day 8 and Day 29)
- PBF-999 half-life in plasma " t½"(Day 1, Day 8 and Day 29)
- Efficacy of PBF-999 as measured by Disease control rate (DCR)(2 years)