A Multicenter, Single-Arm, Phase II Study Evaluating the Efficacy and Safety of Fruquintinib Combined With Serplulimab as First-Line Treatment in Patients With Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Progression-free survival
研究概览
简要总结
This multicenter, single-arm, phase II study (FRONTIER) evaluates the efficacy and safety of fruquintinib combined with serplulimab as first-line treatment in patients with metastatic or unresectable non-clear cell renal cell carcinoma (nccRCC). Given the biological heterogeneity and lack of established standard therapies in nccRCC, this study aims to characterize clinical outcomes and explore potential biomarkers associated with treatment benefit.
详细描述
This is a prospective, multicenter, single-arm phase II study conducted in patients with metastatic or unresectable nccRCC across participating centers in China.
The study consists of a safety run-in phase followed by a cohort expansion phase. Six patients were initially enrolled in the safety run-in stage. As no dose-limiting toxicities or treatment-related deaths were observed during the predefined observation period, the study proceeded to full enrollment. A total of 40 patients were enrolled and received fruquintinib (5 mg orally once daily, 2 weeks on/1 week off) in combination with serplulimab (4.5 mg/kg intravenously every 3 weeks) as first-line systemic therapy.
Tumor assessments were performed at baseline and every 6 weeks during treatment according to RECIST version 1.1 until disease progression, death, or study discontinuation. Investigator assessment is used for the primary progression-free survival endpoint. Objective response rate, disease control rate, and duration of response are assessed by blinded independent central review.
In addition to evaluating clinical efficacy and safety, prespecified exploratory translational analyses are conducted using pretreatment tumor samples. Multiplex immunofluorescence is used to characterize the composition and spatial organization of the pretreatment tumor immune microenvironment.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Age 18 to 85 years
- •Histologically or cytologically confirmed metastatic or unresectable nccRCC
- •At least one measurable lesion per RECIST v1.1
- •No prior systemic therapy for advanced disease
- •ECOG performance status 0-1
- •Adequate organ function
- •Life expectancy ≥3 months
排除标准
- •History of allergy to any component of serplulimab or fruquintinib.
- •History of or concurrent malignancy, excluding skin basal cell carcinoma, cervical carcinoma in situ, and papillary thyroid carcinoma, that has not been cured for more than 5 years or has active cancer.
- •Uncontrolled cardiac symptoms or diseases, including NYHA class II or higher heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant atrial or ventricular arrhythmias requiring intervention.
- •Previous treatment with PD-1, PD-L1, or CTLA-4 antibodies; investigational drugs within 4 weeks before the first dose; enrollment in another interventional clinical trial; systemic corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 2 weeks before the first dose, subject to protocol-specified exceptions; antitumor or live vaccines within 4 weeks; or major surgery or serious trauma within 4 weeks.
- •Toxicity from previous anticancer therapy not recovered to CTCAE grade 1 or lower, excluding alopecia and residual neurotoxicity related to previous platinum therapy, or otherwise not meeting the eligibility criteria.
- •Serious infection (CTCAE grade >2) within 4 weeks before the first dose, including severe pneumonia, sepsis requiring hospitalization, infection-related complications, active pulmonary inflammation on baseline imaging, symptoms or signs of infection, or need for oral or intravenous antibiotics.
- •Active autoimmune disease or history of autoimmune disease, subject to the protocol-specified exceptions for stable thyroid replacement, type 1 diabetes on stable insulin, vitiligo, and childhood asthma or allergy in remission.
- •History of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency, organ transplantation, or allogeneic bone marrow transplantation.
- •History of interstitial lung disease, excluding radiation pneumonitis not treated with steroids, or history of noninfectious pneumonia.
- •Evidence of active tuberculosis infection, active tuberculosis within 1 year before screening, or inadequately treated tuberculosis more than 1 year before screening.
- •Active hepatitis B or hepatitis C as defined in the protocol; eligible patients with controlled hepatitis B must receive protocol-specified antiviral therapy.
- •Known history of psychotropic substance abuse, alcoholism, or drug use.
- •Pregnant or lactating women.
- •Other factors that, in the investigator's judgment, could require withdrawal or compromise patient safety or data collection, including serious concomitant illness, significant laboratory abnormalities, or family or social factors.
- •Severe active bleeding, active peptic ulcers, unhealed gastrointestinal perforations, or gastrointestinal fistulas.
研究组 & 干预措施
Fruquintinib combine with Serplulimab
Patients receive fruquintinib 5 mg once daily, 2 weeks on/1 week off, combined with serplulimab 4.5 mg/kg by intravenous infusion on day 1 every 3 weeks.
干预措施: Fruquintinib combined with Serplulimab (Drug)
结局指标
主要结局
Progression-free survival
时间窗: Up to 2 years
Defined as the time from treatment initiation to the first documentation of disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Investigator-assessed progression-free survival (PFS)
时间窗: Up to 2 years
Time from treatment initiation to the first documentation of disease progression according to RECIST version 1.1, as assessed by the investigator, or death from any cause, whichever occurs first.
次要结局
- Objective Response Rate(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
- Adverse Event(Up to 2 years)
- Objective response rate (ORR) by blinded independent central review(Up to 2 years)
- Disease control rate (DCR) by blinded independent central review(Up to 2 years)