A Phase 1/2, Open-Label, Study to Evaluate the Safety and Anti-Tumor Activity of FS118, a LAG-3/PD-L1 Bispecific Antibody, as a Monotherapy and in Combination With Paclitaxel, in Patients With Advanced Malignancies
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
- Dose escalation: Serum Concentration vs time profile of FS118
研究概览
简要总结
This study will be conducted in adult participants diagnosed with advanced tumors to characterize the safety, tolerability, pharmacokinetics (PK), and activity of FS118. This is a Phase 1/2, multi-center, open-label, multiple-dose, first-in-human study, designed to systematically assess safety and tolerability, to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for FS118 in participants with advanced tumors and to determine the efficacy of FS118 in participants with squamous cell carcinoma of the head and neck (SCCHN) as monotherapy and in combination with paclitaxel. In addition to safety, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •All participants:
- •Age ≥18 years;
- •Participants with histologically confirmed, locally advanced, unresectable, or metastatic solid tumors that progressed while on or after PD-1/PD-L1 containing therapy;
- •Measurable disease;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;
- •Life expectancy estimated to be at least 3 months;
- •Highly effective contraception;
- •Willing and able to provide written informed consent.
- •Expansion cohort only:
- •Histologically and/or cytologically confirmed recurrent/metastatic (R/M) SCCHN that is not amenable to curative therapy by surgery or radiation;
- •Only 1 prior anti-PD-1 or anti-PD-L1 therapy and documented PD-L1 scoring ≥1% by combined positive score or tumor proportion score as part of their treatment;
- •An anti-PD-1 or anti-PD-L1 treatment regimen must be the last prior therapy before study enrollment, following no more than 2 prior systemic regimens for R/M SCCHN;
- •Acquired resistance to an anti-PD-1- or anti-PD-L1-containing therapy;
- •The participant agrees to undergo a pre-treatment and on-treatment core or excisional biopsy and the biopsy procedure is not judged to be high risk by the Investigator.
排除标准
- •All participants:
- •Participant is deemed at high risk of fatal outcome in case of COVID-19;
- •Participants with a history of COVID-19 and have not provided a negative test for SARS CoV-2 infection within 28 days of the planned first dose date with FS118;
- •Prior therapy: Received systemic anti-cancer therapy within 28 days or 5 half-lives, of the first dose of study drug, or prior treatment with a LAG-3 inhibitor;
- •Participants with active or documented history of autoimmune disease;
- •History of uncontrolled intercurrent illness;
- •Known infections;
- •Uncontrolled CNS metastases, primary CNS tumors, or solid tumors with CNS metastases as only measurable disease;
- •Prior history of or active interstitial lung disease or pneumonitis, encephalitis, seizures, severe immune related adverse events with prior PD-1/PD-L1 containing treatments;
- •Significant cardiac abnormalities;
- •Significant laboratory abnormalities;
- •Intolerance to the investigational product or its excipients, or any condition that would significantly impair and/or prohibit the participants's participation in the study, as per the Investigator's judgment.
- •Expansion cohort only:
- •Participant has nasopharynx or thyroid primary tumor site;
- •History of severe immune-related toxicity during the prior treatment with checkpoint inhibitors.
研究组 & 干预措施
FS118 weekly
The initial cohorts will enroll sequentially as single-participant cohorts. If no DLT or ≥Grade 2 study drug related adverse event is observed, then dosing will proceed in a 3+3 design followed by an expansion cohort of participants with SCCHN and an expansion SCCHN cohort in combination with Paclitaxel.
干预措施: FS118 (Drug)
FS118 weekly
The initial cohorts will enroll sequentially as single-participant cohorts. If no DLT or ≥Grade 2 study drug related adverse event is observed, then dosing will proceed in a 3+3 design followed by an expansion cohort of participants with SCCHN and an expansion SCCHN cohort in combination with Paclitaxel.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Dose escalation: Serum Concentration vs time profile of FS118
时间窗: 7 months
Blood samples for serum PK analysis will be obtained (concentrations measured in mcg/mL)
Dose escalation: Time to reach maximum serum concentration (Tmax) of FS118
时间窗: 7 months
Blood samples for serum PK analysis will be obtained (Tmax measured in hours)
Dose escalation: Trough serum concentration (Ctrough) of FS118 prior to the next dose
时间窗: 7 months
Blood samples for serum PK analysis will be obtained (Ctrough measured in mcg/mL)
Expansion cohort (FS118 + paclitaxel): Incidence of Treatment Emergent Adverse Events (safety and Tolerability) Incidence, severity and duration of adverse events
时间窗: 12 months
Assessed by CTCAE v 5.0
Expansion cohort: Disease control rate as assessed by RECIST 1.1 in evaluable participants with PD-L1 and LAG-3 positive SCCHN
时间窗: 24 weeks
Assessed by RECIST 1.1
Dose escalation: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
时间窗: 12 months
Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03
Dose escalation: Maximum Serum Concentration of FS118
时间窗: 7 months
Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)
Dose escalation: Area under the serum FS118 concentration vs time Curve (AUC)
时间窗: 7 months
Blood samples for serum PK analysis will be obtained (AUC measured in d.mcg/mL)
Dose escalation: Systemic Clearance (CL) of FS118
时间窗: 7 months
Blood samples for serum PK analysis will be obtained (CL measured in mL/day)
次要结局
- Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST(7 months)
- Expansion cohort: Disease Response as assessed by RECIST 1.1 and iRECIST in all SCCHN participants(24 months)
- Expansion cohort: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)(12 months)
- Expansion cohort: Trough serum concentration (Ctrough) of FS118 prior to the next dose(7 months)
- Expansion cohort: Area under the serum FS118 concentration vs time Curve (AUC)(7 months)
- Dose escalation and expansion cohort of FS118 + paclitaxel(7 months)
- Expansion cohort: Time to reach maximum serum concentration (Tmax) of FS118(7 months)
- Expansion cohort: Maximum Serum Concentration of FS118(7 months)
- Expansion cohort: Systemic Clearance (CL) of FS118(7 months)