A Multicenter, Single-Arm, Phase II Study of Cadonilimab (AK104) Plus Lenvatinib in Patients With Advanced/Metastatic Clear Cell Renal Cell Carcinoma Previously Treated With Immunotherapy-Based Combination Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- ORR per RECIST v1.1 as assessed by investigators
研究概览
简要总结
This is a phase II, open-label, multicenter, single-arm study evaluating the efficacy and safety of cadonilimab (AK104) in combination with lenvatinib in patients with unresectable advanced or metastatic clear cell renal cell carcinoma (ccRCC) who experienced disease progression during or after prior first-line immunotherapy-based combination therapy. Patients receive cadonilimab plus lenvatinib until radiographic disease progression, unacceptable toxicity, withdrawal of consent, death, or investigator decision. The primary endpoint is objective response rate (ORR) according to RECIST version 1.1 as assessed by investigators.
详细描述
This is a multicenter, open-label, single-arm phase II clinical trial with a planned enrollment of 28 patients with unresectable advanced or metastatic clear cell renal cell carcinoma (ccRCC). Participating centers include Renji Hospital and Ruijin Hospital in Shanghai, China.
Patients receive oral lenvatinib at a starting dose of:
8 mg once daily for body weight <60 kg 12 mg once daily for body weight ≥60 kg Cadonilimab (AK104) is administered intravenously at 10 mg/kg every 3 weeks. Treatment continues until radiographic disease progression, unacceptable toxicity, withdrawal of informed consent, initiation of new anticancer therapy, death, loss to follow-up, or investigator decision.
Tumor assessments are performed at baseline, every 6 weeks (±7 days) during treatment, and at the end-of-treatment visit.
This study uses Simon's optimal two-stage phase II design. In stage 1, 12 evaluable patients are enrolled for futility assessment. If 2 or fewer confirmed objective responses are observed, the study may be terminated early for futility. Otherwise, enrollment proceeds to a total of 28 evaluable patients.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Criteria: Inclusion Criteria:
- •Written informed consent provided prior to study procedures.
- •Age ≥18 and ≤80 years at the time of consent.
- •Histologically or cytologically confirmed renal cell carcinoma with clear cell component.
- •Unresectable locally advanced or metastatic disease.
- •Radiographic disease progression during or after prior first-line immunotherapy-based combination therapy for advanced RCC.
- •At least one measurable lesion according to RECIST v1.
- •ECOG performance status of 0 or
- •Estimated life expectancy of at least 3 months.
- •Adequate organ function, including hematologic, renal, hepatic, and coagulation parameters, as defined in the protocol.
排除标准
- •History of hypersensitivity to monoclonal antibodies or any component of cadonilimab or lenvatinib.
- •Known additional malignancy that is progressing or has required active treatment. Exceptions include adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ.
- •Prior treatment with dual immune checkpoint blockade, defined as anti-PD-1/PD-L1 combined with anti-CTLA-4 therapy.
- •Uncontrolled clinically significant cardiovascular disease or symptoms.
- •Diagnosis of immunodeficiency or receipt of systemic corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive therapy within 14 days prior to first dose.
- •Active autoimmune disease or history of autoimmune disease that may worsen with immunostimulatory therapy. Subjects with type 1 diabetes mellitus, vitiligo, psoriasis, or hypo-/hyperthyroidism not requiring immunosuppressive treatment are eligible.
- •History of non-infectious pneumonitis requiring steroids or current pneumonitis/interstitial lung disease.
- •Active tuberculosis or active syphilitic infection.
- •Known history of human immunodeficiency virus (HIV) infection.
- •Active hepatitis B infection (HBsAg positive with HBV DNA >500 IU/mL) or active hepatitis C infection (detectable HCV RNA).
- •Clinically significant toxicities from prior anticancer therapy not recovered to Grade ≤1 (except alopecia or stable endocrinopathies).
- •Active bleeding disorder or history of clinically significant bleeding episodes.
- •Drug abuse, psychiatric illness, or medical/social conditions that may interfere with study participation or evaluation of results.
- •Pregnant or breastfeeding women, or participants planning conception during the study treatment period.
研究组 & 干预措施
AK104 combine with lenvatinib
Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(<60kg，8 mg qd；≥60kg，12mg qd, orally.
干预措施: AK104（anti-PD-1/CTLA-4 bi-specific antibody ，intravenously）,lenvatinib（ targeted VEGFR 1-3、FGFR、PDGFRα， small molecule TKI，orally (Drug)
结局指标
主要结局
ORR per RECIST v1.1 as assessed by investigators
时间窗: Up to 2 years
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1
次要结局
- Duration of response (DOR)(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
- Time to response（TTR）(Up to 2 years)
- Progression-free survival (PFS)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)