Phase I/Ib Trial of Single Agent MBF-362 in Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 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
研究概览
简要总结
This is an open, single center Phase Iclinical trial to evaluate the safety, tolerability, and preliminary efficacy of MBF-362 in patients with solid tumors.
详细描述
The phase I dose escalation will be conducted utilizing the standard 3+3 dose escalation method. Pharmacokinetic (PK) data will be obtained for MBF-362.
The phase I dose expansion will consist of 1 group including 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 MBF-362 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 MBF-362 dose.
Patients must have histologically or cytologically confirmed cancer with at least one measurable lesion, with adequate organ and marrow function, and with ECOG performance status of 0-1. Eligible patients must have received at least one prior line of therapy for their disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •These criteria are similarly applicable to patients enrolled to the phase I dose escalation and to the phase IB dose expansion portions of the trial.
- •Advanced/metastatic histologically confirmed solid tumor. All types of solid tumors are allowed in the study
- •At least 1 measurable lesion per Response Evaluation Criteria in solid tumor (RECIST 1.1).
- •Patients who have progressed to the standard therapy and have no approved optional therapy available.
- •ECOG performance status of 0/1
- •Age greater than 18 years (inclusive).
- •Adequate bone marrow, renal and hepatic function
- •Able and willing to give valid written consent for available archival tumor samples (mandatory) and tumor biopsies before and during protocol (immune)therapy (optional in escalation phase and mandatory in expansion phase).
- •Prior immunotherapy is also allowed.
排除标准
- •These criteria are similarly applicable to patients enrolled to the phase I dose escalation and to the phase IB dose expansion portions of the trial.
- •Participation in another clinical study with an investigational product during the last 4 weeks or 5 half-lives 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 oral or systemic steroids 2 weeks prior to dosing with MBF-362
- •Patients receiving >4 doses of anti-inflammatory (NSAID) treatments, modulators of the COX-2 pathway or aspirin 1 week prior to dosing with MBF-362
- •Patients with a history of gastric/duodenal ulcers, colitis and/or gastrointestinal bleeding, severe gastrointestinal adverse reactions
- •Patients with a history of anaphylaxis, uncontrolled asthma or allergy/hypersensitivity/intolerance to NSAIDs, COX-2 inhibitors or aspirin.
研究组 & 干预措施
MBF-362 772.2 mg
Drug: Six MBF-362 128.7 mg hard gelatin capsule EP2/EP4 antagonist 28 days single oral daily dosing cycles
干预措施: MBF-362 (Drug)
MBF-362 514.8 mg
Drug: Four MBF-362 128.7 mg hard gelatin capsules EP2/EP4 antagonist 28 days single oral daily dosing cycles
干预措施: MBF-362 (Drug)
MBF-362 257.4 mg
Drug: Two MBF-362 128.7 mg hard gelatin capsules EP2/EP4 antagonist 28 days single oral daily dosing cycles
干预措施: MBF-362 (Drug)
MBF-362 128.7 mg
Drug: One MBF-362 128.7 mg hard gelatin capsule EP2/EP4 antagonist 28 days single oral daily dosing cycles
干预措施: MBF-362 (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
时间窗: 28 Days
AEs will be described by system organ class and preferred tem using the Medical Dictionary for Regulatory Activities (MedDRA)
The Maximun Tolerated Dose (MTD) of MBF-362
时间窗: 28 Days
The MTD evaluation will be based on the DLT Evaluable Population which includes all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with MBF-362 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 MBF-362 treatment as measured by overall survival (OS)(2 years)
- Efficacy of MBF-362 treatment as measured by Objective response rate (ORR)(2 years)
- The area under MBF-251 plasma concentration-time curve to infinite time "AUC(0-inf)(Between day 1 and 2, and day 8 and 9 of cycle 1, and between day 1 and 2 of cycle 2 (each cycle is 28 days))
- Efficacy of MBF-362 treatment as measured by Disease control rate (DCR)(2 years)
- Efficacy of MBF-362 treatment as measured by duration of response (DoR)(2 years)
- Time to MBF-251 peak concentration in plasma "Tmax"(Between day 1 and 2, and day 8 and 9 of cycle 1, and between day 1 and 2 of cycle 2 (each cycle is 28 days))
- MBF-251 peak concentration in plasma "Cmax"(Between day 1 and 2, and day 8 and 9 of cycle 1, and between day 1 and 2 of cycle 2 (each cycle is 28 days))
- Efficacy of MBF-362 treatment as measured by progression-free survival (PFS)(2 years)
- MBF-251 half-life in plasma " t½"(Between day 1 and 2, and day 8 and 9 of cycle 1, and between day 1 and 2 of cycle 2 (each cycle is 28 days))