A Phase 1a/1b Study of FPT155 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 80
- 试验地点
- 12
- 主要终点
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This study is a Phase 1 open-label, first-in-human, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and activity of FPT155 as monotherapy in patients with advanced solid tumors.
详细描述
This Phase 1 study is comprised of dose escalation and cohort expansions for FPT155 monotherapy and for FPT155 in combination with pembrolizumab. Monotherapy dose escalation is designed with initial accelerated titration followed by a standard 3+3 dose escalation; combination dose escalation uses a standard 3+3 design. Patients will remain on study treatment until progression of disease, unacceptable toxicity, or other specified reason for discontinuation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Histologically confirmed solid tumors (except primary central nervous system tumors). For patients enrolled for treatment with FPT155+pembrolizumab: histologically confirmed non-small cell lung cancer not eligible for curative therapy.
- •Disease that is unresectable, locally advanced, or metastatic and has progressed following all standard treatments or is not appropriate for standard treatments
- •All patients must have at least one measurable lesion at baseline according to RECIST v1.1
- •Availability of archival tumor tissue and consent to provide archival tumor for retrospective biomarker analysis, or consent to undergo a fresh tumor biopsy during screening
- •For patients participating in cohort expansions: consent to undergo a mandatory fresh tumor biopsy during screening and on treatment
- •ECOG performance status of 0 or 1
- •Prior radiotherapy must be completed at least 2 weeks before first dose of study treatment administration. No radiopharmaceuticals (eg, strontium, samarium) within 8 weeks before first dose of study treatment administration.
- •Prior surgery that requires general anesthesia must be completed at least 14 days before first dose of study treatment
- •Adequate bone marrow, liver and kidney function
排除标准
- •Uncontrolled or significant cardiac disease
- •Any uncontrolled medical condition or psychiatric disorder including infection, autoimmune disease, bleeding disorder or symptomatic involvement of the central nervous system
- •Treatment with any anti-cancer therapy or participation in another investigational drug or biologics trial within 28 days or ≤ 5 half-lives (whichever is shorter)
- •Patients who discontinue prior immune-modulating therapies (including regimens containing an immune agonist or a PD-L1/PD-1 antagonist) due to toxicity or have received treatment within 5 half lives or 90 days
- •Pregnancy or breastfeeding
- •For patients participating in cohort expansion: Prior treatment with a CTLA-4 antagonist, including ipilimumab and tremelimumab
研究组 & 干预措施
FPT155 monotherapy
The study consists of dose escalation and cohort expansions
干预措施: FPT155 (Biological)
FPT155 in combination with pembrolizumab
The study consists of dose escalation and cohort expansions
干预措施: FPT155 (Biological)
FPT155 in combination with pembrolizumab
The study consists of dose escalation and cohort expansions
干预措施: pembrolizumab (Biological)
结局指标
主要结局
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
时间窗: Median (min, max) duration of FPT155 exposure was 6.57 [3.0, 49.6] weeks for the Phase 1a Monotherapy part of the study, 8.29 [3.0, 27.1] weeks for the Phase 1b Monotherapy, and 14.71 [3.0, 25.1] weeks for the Phase 1a Combination
TEAE was defined as an adverse event (AE) that was not present prior to the start date of study drug or was worsened during treatment and 100 days after last dose of treatment. An AE that was present at treatment initiation but resolved and then reappeared and the event severity increase while the participant was on treatment is also a TEAE. A severe AE (SAE) is defined as any untoward medical occurrence that at any dose: Is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, and is a congenital anomaly/birth defect. AEs were graded 1 (mild)-5 (fatal AE) according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03.
Phase 1a Monotherapy: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days
DLTs ware defined as any of the events that occurred during the first 28 days of treatment and were assessed by the Clinical Research Coordinator (CRC) as related to FPT155.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Discontinued Due to AEs
时间窗: Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
Represents the number of participants who had discontinuation of FPT155 dosing due to AEs.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Modified Due to AEs
时间窗: Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
Represents the number of participants who had a modification in the dosing schedules of FPT155 due to AEs.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Interrupted Due to AEs
时间窗: Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
Represents the number of participants who had an interruption in the dosing schedules of FPT155 due to AEs.
Phase 1a Combination: Number of Participants Who Experienced DLTs
时间窗: Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days
DLTs ware defined as any of the events that occur during the first 28 days of treatment and are assessed by the CRC as related to FPT155.
次要结局
- Phase 1a Monotherapy: Area Under Serum Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval) (AUC0-tau) of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1a Monotherapy: Maximum Observed Serum Concentration (Cmax) of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1a Monotherapy: Trough Observed Serum Concentration at the End of Each Dose Interval (Ctrough) of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1a Monotherapy: Clearance (CL) of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1a Monotherapy: Terminal Half-life (t1/2) of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1a Monotherapy: Volume of Distribution at Steady State (Vss) of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1a Monotherapy: Number of Participants With Treatment-emergent Anti-FPT155 Antibody Response(Cycle 1 (21-day cycles) Day 1)
- Phase 1b Monotherapy: Objective Response Rate (ORR) Per RECIST v1.1(Up to approximately 30 months)
- Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1(Up to approximately 30 months)
- Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1(Up to approximately 30 months)
- Phase 1b Monotherapy: Disease Control Rate (DCR) Per RECIST v1.1(Up to approximately 30 months)
- Phase 1b Monotherapy: AUC0-tau of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1b Monotherapy: Cmax of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1b Monotherapy: Ctrough of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1b Monotherapy: CL of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1b Monotherapy: t1/2 of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1b Monotherapy: Vss of FPT155(Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15)
- Phase 1b Monotherapy: Number of Participants With Treatment-emergent Anti-FPT155 Antibody Response(Cycle 1 (21-day cycles) Day 1)
- Phase 1a Combination: ORR Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Up to approximately 30 months)