A Prospective, Single-Arm, Multicenter Clinical Study of High-Risk Localized and Locally Advanced Renal Clear Cell Carcinoma

NCT07741617 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: QL-RCC-QIBA-3010
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urologic Neoplasms

Keywords

high risk; locally advanced; ccECC

Outcome Measures

Primary Outcomes (1)

• 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).

  every 6 weeks to 2 years assessed by the investigator per RECIST v1.1.

Secondary Outcomes (2)

• 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

Study Arms (1)

TREATMENT GROUP（Iparomlimab and Tuvonralimab in combination with Lenvatinib ）

EXPERIMENTAL

Summary of Neoadjuvant and Adjuvant Treatment Periods 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.

Drug: Iparomlimab and Tuvonralimab in combination with Lenvatinib

Interventions

Iparomlimab and Tuvonralimab in combination with Lenvatinib DRUG

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.

TREATMENT GROUP（Iparomlimab and Tuvonralimab in combination with Lenvatinib ）

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 cM0.
• No prior treatment with any immune checkpoint inhibitor.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy ≥ 3 months.
• At least one measurable lesion according to RECIST v1.1.
• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead
• Wuxi No. 2 People's Hospital: collaborator
• Changzhou No.2 People's Hospital: collaborator

Study Sites (1)

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210000, China

Location

MeSH Terms

Conditions

Urologic Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases

Central Study Contacts

Hongqian Guo, Chief Physician

CONTACT

025-83106666; dr.ghq@163.com

Changwei Ji, Chief Physician

CONTACT

+86 19822681999; jichangwei@nju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ward Director

Model Details: Summary of Neoadjuvant and Adjuvant Treatment Periods 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.

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: August 3, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2030
• Last Updated: August 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)