A Prospective, Single-Arm, Multicenter Clinical Study of Epalolitoworelimab (a PD-1/CTLA-4 Combination Antibody) Combined With Lenvatinib in the Perioperative Treatment of High-Risk Localized and Locally Advanced Renal Clear Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Objective Response Rate(ORR)
研究概览
简要总结
Study Design Prospective, single-arm, multicenter clinical study.
Study Drugs
Neoadjuvant phase: QL1706 (Aipaluo Tuoworilimab, an anti-PD-1/CTLA-4 combination antibody) plus lenvatinib.
Adjuvant phase: QL1706 monotherapy.
Target Population Patients with high-risk localized or locally advanced clear cell renal cell carcinoma (ccRCC) meeting AJCC staging criteria (e.g., cT3a G3-4 cN0M0, etc.) who are candidates for neoadjuvant therapy and surgical resection.
Treatment Flow
Screening (28 days): Informed consent obtained, baseline assessments completed.
Neoadjuvant phase (4 cycles, 21 days/cycle):
QL1706 5 mg/kg IV, Q3W; plus oral lenvatinib 12 mg QD.
Efficacy evaluation every 2 cycles; surgery after 4 cycles (unless early termination).
Adjuvant phase (13-17 cycles, 21 days/cycle):
Eligible patients continue QL1706 5 mg/kg IV, Q3W.
Imaging every 3 months until recurrence, new therapy, death, or completion of 21 cycles total.
Follow-up: Safety follow-up (90 days after last QL1706 dose or 30 days after last other drug, whichever is longer), then survival follow-up every 90 days.
Endpoints
Primary: Objective response rate (ORR) per RECIST 1.1.
Secondary: Pathological complete response rate (pCR), median disease-free survival (mDFS), 12-/24-month DFS rates, median overall survival (mOS), and safety.
Sample Size Planned enrollment: 54 subjects.
详细描述
This is a prospective, single-arm, multicenter clinical study designed to evaluate the efficacy and safety of **QL1706** (an anti-PD-1/CTLA-4 combination antibody, also known as *Aipaluo Tuoworilimab*) combined with **lenvatinib** as neoadjuvant therapy for high-risk localized and locally advanced clear cell renal cell carcinoma (ccRCC), followed by QL1706 monotherapy as postoperative adjuvant therapy.
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**Study Population**
Patients with histologically or cytologically confirmed locally advanced or high-risk localized clear cell renal cell carcinoma who are candidates for neoadjuvant therapy and surgical resection, defined by the following staging criteria (AJCC):
- **Locally advanced (Stage III ccRCC):**
- cT3a G3-4 cN0 M0;
- cT3b-T4 G<sub>any</sub> cN0 M0;
- cT<sub>any</sub> cN1 G<sub>any</sub> M0;
- **High-risk localized ccRCC:**
- cT1b G4 or with sarcomatoid features, cN0 cM0;
- cT2 G3-4, cN0 M0.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and agree to comply with the study requirements and assessment schedule, and voluntarily provide written informed consent (ICF) prior to any trial-related procedures.
- •Age ≥ 18 years and ≤ 75 years, male or female.
- •Histologically or cytologically confirmed localized and locally advanced clear cell renal cell carcinoma.
- •Locally advanced renal cell carcinoma (stage III per AJCC): cT3a G3-4 cN0 M0; cT3b-T4 Gany cN0 M0; cTany cN1 Gany cM0; or high-risk localized renal cell carcinoma: cT1b G4 or with sarcomatoid features cN0 cM0; cT2 G3-4 cN0 cM
- •No prior treatment with any immune checkpoint inhibitor.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Life expectancy ≥ 3 months.
- •At least one measurable lesion according to RECIST v1.
- •Planned to receive neoadjuvant therapy and surgical resection.
- •Adequate major organ function within 7 days prior to treatment, meeting the following criteria: A. Hematology: absolute neutrophil count ≥ 1.5 × 10⁹/L; hemoglobin ≥ 80 g/L; platelet count ≥ 90 × 10⁹/L. B. Blood biochemistry: total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN (for subjects with liver metastases, ALT or AST ≤ 5 × ULN is permitted); serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min. C. Left ventricular ejection fraction ≥ 50%. D. Activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) ≤ 1.5 × ULN. E. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or free T3) and free T4 within the normal range are also eligible. F. Cardiac enzymes and troponin within normal limits (isolated laboratory abnormalities deemed clinically insignificant by the investigator are also allowed).
- •Female subjects of childbearing potential must agree to use effective contraception (e.g., intrauterine device, contraceptive pill, or condom) during the study and for 6 months after study completion; serum pregnancy test must be negative within 72 hours prior to the first dose, and they must not be breastfeeding. Male subjects must agree to use effective contraception during the study and for 6 months after study completion.
排除标准
- •Presence of symptomatic or untreated known brain metastases or other central nervous system (CNS) metastases. CNS metastases that have been completely resected and/or irradiated with documented stability or improvement are not exclusionary, provided that computed tomography (CT) shows stability for at least 4 weeks prior to screening, with no evidence of cerebral edema and no requirement for glucocorticoids or anticonvulsants
- •Patients with advanced or metastatic renal cell carcinoma, or non-clear cell renal cell carcinoma
- •Known hypersensitivity to the investigational product or any of its excipients; or previous allergy to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
- •Prior discontinuation of immunotherapy due to severe and/or life-threatening immune-related adverse events
- •Adverse events from prior anti-tumor therapy have not recovered to ≤ Grade 1 per NCI-CTCAE v5.0 at enrollment (except for alopecia or other toxicities deemed by the investigator to be tolerable and not clinically significant)
- •Presence of any active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients on hormone replacement therapy may be considered for inclusion); patients with psoriasis or childhood asthma/allergy that has completely resolved and requires no intervention in adulthood may be considered, but those requiring bronchodilators for medical intervention are excluded
- •History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation.
- •Presence of poorly controlled cardiac symptoms or diseases, including but not limited to: heart failure ≥ NYHA class II, unstable angina, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias that have not been clinically intervened or remain poorly controlled after intervention
- •Severe infection (CTCAE > Grade 2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; active pulmonary inflammation on baseline chest imaging; signs or symptoms of infection or need for oral or intravenous antibiotic therapy within 14 days prior to the first dose of study drug (prophylactic antibiotics are allowed).
- •Active pulmonary tuberculosis infection identified by history or CT, or history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago without adequate treatment.
- •Positive HBV DNA test; hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of quantification of the assay).
- •Diagnosis of another malignancy within 5 years prior to the first dose of study drug, except for malignancies with low risk of metastasis or death, such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ, which may be considered for enrollment.
- •Known hereditary or acquired bleeding or thrombotic tendency (e.g., hemophilia, coagulation disorders, thrombocytopenia, etc.), or currently receiving thrombolytic or anticoagulant therapy.
- •Clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment, such as daily hemoptysis ≥ 2.5 mL, lower gastrointestinal bleeding, esophageal-gastric varices with bleeding risk, bleeding gastric ulcer, or vasculitis, etc.
- •Arterial/venous thrombotic events occurring within 6 months prior to enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
- •Pregnant or breastfeeding female patients.
- •According to the investigator's judgment, any other factors that may compel premature termination of the study, such as other serious concomitant diseases (including psychiatric disorders) requiring concomitant treatment, alcoholism, drug abuse, family or social factors that may affect subject safety or compliance.
- •Currently participating in another clinical study, unless it is an observational (non-interventional) clinical study or follow-up of an interventional study.
结局指标
主要结局
Objective Response Rate(ORR)
时间窗: every 6 weeks to 2 years assessed by the investigator per RECIST v1.1.
During the neoadjuvant treatment phase, the objective response rate (ORR) is defined as the percentage of subjects who achieve complete response (CR) or partial response (PR).
次要结局
- Pathological Complete Response Rate(pCR)(within 1-4 weeks postoperatively,Pathological assessment)
- Disease-Free Survival(DFS)(within 2 years after surgery,imaging follow-up evaluation)
研究者
Hongqian Guo
Ward Director
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School