A Phase I, Open Label, Dose Escalation and Dose Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumour Activity of IPN60090 as Single Agent and in Combination in Patients With Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Ipsen
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) in Part A
研究概览
简要总结
The purpose of the protocol is to determine safety, tolerability, recommended dose (RD), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity of IPN60090 as a single agent (Part A) and in combination with pembrolizumab (Part B) or paclitaxel (Part C) in patients with advanced solid tumours and to evaluate food effect (Part D).
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
- 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
- •Male or female patients ≥18 years of age
- •Patients with solid tumours who have received at least one line of therapy for advanced disease
- •Measurable or non-measurable evaluable disease per RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1
- •Standard of care and/or any investigational therapies must have been completed at least 3 weeks prior to treatment
排除标准
- •Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder
- •Known primary central malignancy or symptomatic central nervous system metastasis
- •Major surgical intervention within 28 days before study drug administration
- •Significant acute or chronic infections
研究组 & 干预措施
IPN60090
Part 1: Dose escalation of IPN60090, Part 2: Dose expansion
IPN60090 given as a Bis in Die (BID) oral dose administered up to Maximum Tolerated Dose (MTD) over a 21-day cycle
干预措施: IPN60090 (Drug)
IPN60090 in combination with pembrolizumab
Part 1: Dose escalation of IPN60090 in combination with pembrolizumab, Part 2: Dose expansion
IPN60090 given as a Bis in Die (BID) oral dose, starting with pharmacologically active dose identified in 1dose escalation of IPN60090 as a single agent, over a 21-day cycle in combination with 200 mg pembrolizumab given every 21 days (Day 1 of every cycle) as IV infusion
干预措施: IPN60090 (Drug)
IPN60090 in combination with pembrolizumab
Part 1: Dose escalation of IPN60090 in combination with pembrolizumab, Part 2: Dose expansion
IPN60090 given as a Bis in Die (BID) oral dose, starting with pharmacologically active dose identified in 1dose escalation of IPN60090 as a single agent, over a 21-day cycle in combination with 200 mg pembrolizumab given every 21 days (Day 1 of every cycle) as IV infusion
干预措施: pembrolizumab (Drug)
IPN60090 in combination with paclitaxel
Part 1: Dose escalation of IPN60090 in combination with paclitaxel, Part 2: Dose expansion
IPN60090 given as a BID oral dose, starting with pharmacologically active dose identified in dose escalation of IPN60090 as a single agent over a 21-day cycle in combination with 175 mg/m2 or 135 mg/m2 paclitaxel given every 21 days (Day 1 of every cycle) as IV infusion
干预措施: IPN60090 (Drug)
IPN60090 in combination with paclitaxel
Part 1: Dose escalation of IPN60090 in combination with paclitaxel, Part 2: Dose expansion
IPN60090 given as a BID oral dose, starting with pharmacologically active dose identified in dose escalation of IPN60090 as a single agent over a 21-day cycle in combination with 175 mg/m2 or 135 mg/m2 paclitaxel given every 21 days (Day 1 of every cycle) as IV infusion
干预措施: paclitaxel (Drug)
IPN60090 food effect
Part 1: Food Effect of IPN60090
IPN60090 given as a single oral dose as a single agent at the recommended dose (RD) under fasting and fed conditions followed by IPN60090 given as a BID oral dose administered at the RD over a 21-day cycle.
干预措施: IPN60090 single administration (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) in Part A
时间窗: TEAEs were to be collected from the start of the first dose of IPN60090 (Cycle 1 Day 1) up to 30 days after the date of the decision to permanently discontinue study treatment, assessed until data cut-off for study termination (maximum of 219 days).
An adverse event (AE) is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a study drug, whether or not considered causally related to the study drug. An undesirable medical condition can be symptoms, signs or the abnormal results of an investigation. An SAE is any AE that: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in congenital anomaly or birth defect; or is medically important. A TEAE is defined as any AE that began or worsened following the first administration of study drugs. AEs were recorded and graded according of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. * Grade 1 = mild, * Grade 2 = moderate, * Grade 3 = severe, * Grade 4 = life threatening/disabling, * Grade 5 = death (related to AE).
Number of Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 of Part A
时间窗: Up to Cycle 1 Day 21 of Part A
The maximum tolerated dose (MTD) is defined as the maximum dose of IPN60090 administered BID for 21 days, so that no more than 30% of participants experience a DLT. The MTD was determined using a Bayesian Optimal Interval design. The DLT assessment period was the first 21 days of treatment (one cycle).
Recommended Dose of IPN60090 in Part A
时间窗: Up to Cycle 1 Day 21 of Part A
The recommended dose was determined by the safety review committee following an ad-hoc review of the safety and tolerability data during Part A of the study.
次要结局
- Best Overall Response (BOR) in Part A(RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).)
- Objective Response Rate (ORR) in Part A(RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).)
- Disease Control Rate (DCR) in Part A(RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).)
- Mean Progression Free Survival (PFS) in Part A(RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).)
- Mean Overall Survival (OS) in Part A(RECIST assessments performed at baseline (within 28 days before start of study drug), every 6 weeks +/-1 week for first 24 weeks, then every 12 weeks +/-2 weeks thereafter. Up to data cut-off for study termination (maximum of 247 days).)
- Mean Best Percent Change From Baseline in the Sum of Diameters of the Target Lesions at Minimum Post-Baseline in Part A(Baseline (within 28 days before start of study drug) and post-baseline, up to data cut-off for study termination (maximum of 247 days).)
- Maximum Observed Concentration (Cmax) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A)
- Time to Reach Maximum Observed Concentration (Tmax) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A)
- Trough Plasma Concentration (Ctrough) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 14 in Part A)
- Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 14 in Part A)
- Apparent Elimination Half-Life (T1/2) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A)
- Apparent Total Body Clearance (CL/F) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A)
- Apparent Volume of Distribution (Vz/F) of IPN60090 in Part A(Pre-dose and 0.5, 1, 2, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 in Part A)
- Target Engagement in Part A(At 2 and 12 hours postdose on Cycle 1 Day 1; predose, 2 and 12 hours postdose on Cycle 1 Day 14; and predose, 2 and 2-4 hours postdose on Cycle 1 Day 15 in Part A)