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.
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. \--- \*\*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. \*\*Study Phases\*\* The study consists of four phases: \*\*Screening\*\*, \*\*Neoadjuvant Treatment\*\*, \*\*Postoperative Adjuvant Treatment\*\*, and \*\*Follow-up\*\*. * \*\*Screening Period (28 days):\*\* After signing informed consent, eligible subjects undergo screening evaluations and assessments. Those who meet all inclusion/exclusion criteria proceed to treatment. \*\*Neoadjuvant Treatment Period (21-day cycles)\*\* * From Cycle 1, on Day 1 of each cycle, subjects receive QL1706 \*\*5 mg/kg\*\* intravenously, Q3W, for \*\*4 cycles\*\*. If the infusion is interrupted, the total interruption time is permitted to be ≤8 hours (at room temperature). * Concurrently, from Cycle 1, subjects receive oral lenvatinib \*\*12 mg\*\* once daily (QD) for \*\*4 cycles\*\* (21 days/cycle). * Tumor response is evaluated every \*\*2 cycles\*\* using RECIST 1.1. * Subjects proceed to surgical resection after completion of 4 cycles, unless a termination event occurs (clinical progression, radiographic progression confirmed by the investigator per RECIST 1.1, unacceptable toxicity, withdrawal of informed consent, or meeting criteria for treatment discontinuation). \*\*Adjuvant Treatment Period (21-day cycles)\*\* * Based on postoperative pathology results, subjects who are eligible for adjuvant immunotherapy (as assessed by the investigator and with patient consent) will receive adjuvant therapy. * QL1706 \*\*5 mg/kg\*\* is administered intravenously on Day 1 of each 21-day cycle for \*\*13-17 cycles\*\*. Infusion interruption is allowed for a total of ≤8 hours (at room temperature). * Imaging assessments are performed every \*\*3 months (±7 days)\*\* after treatment initiation until recurrence/metastasis, initiation of new anti-cancer therapy, withdrawal of consent, or death, or until a maximum of \*\*21 cycles\*\* of treatment (whichever occurs first). Additional imaging may be performed at any time if clinically indicated. At the end of treatment, subjects undergo safety assessments and imaging evaluations, followed by a safety follow-up visit up to \*\*90 days after the last dose of QL1706\*\* or \*\*30 days after the last dose of other study drugs\*\* (whichever is longer). After the safety follow-up, survival follow-up is performed every \*\*90 days (±7 days)\*\* to collect and record survival status and subsequent anti-cancer treatments. \--- \*\*Study Endpoints\*\* * \*\*Primary endpoint:\*\* Objective response rate (ORR) assessed by the investigator per RECIST 1.1. * \*\*Secondary endpoints:\*\* Pathological complete response rate (pCR rate), median disease-free survival (mDFS), 12-month and 24-month DFS rates, median overall survival (mOS), and safety profile. \*\*Sample Size\*\* The study plans to enroll \*\*54 subjects\*\*.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Neoadjuvant phase (4 cycles, 21 days/cycle): From Cycle 1, Day 1: IV QL1706 (anti-PD-1/CTLA-4) 5 mg/kg Q3W for 4 cycles. Infusion interruptions allowed up to 8 hours total at room temperature. Concurrent oral lenvatinib 12 mg once daily for 4 cycles. Tumor response assessed every 2 cycles. After 4 cycles, subjects proceed to surgery unless early termination occurs due to clinical/radiographic progression (RECIST 1.1), unacceptable toxicity, consent withdrawal, or meeting discontinuation criteria. Adjuvant phase (13-17 cycles, 21 days/cycle): Based on postoperative pathology and investigator assessment, eligible patients (with consent) continue treatment. QL1706 5 mg/kg IV on Day 1 of each cycle, for 13-17 cycles. No lenvatinib in this phase. Key endpoints (implicit): safety and efficacy (ORR, pCR, DFS, OS) - but the summary focuses on treatment procedures as requested.
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, China
Objective Response Rate(ORR)
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).
Time frame: every 6 weeks to 2 years assessed by the investigator per RECIST v1.1.
Pathological Complete Response Rate(pCR)
After neoadjuvant treatment, subjects undergo surgical resection, and the percentage of subjects who achieve pathological complete response (pCR) on pathological evaluation is calculated.
Time frame: within 1-4 weeks postoperatively,Pathological assessment
Disease-Free Survival(DFS)
Time from surgery to disease recurrence or metastasis.
Time frame: within 2 years after surgery,imaging follow-up evaluation
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