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.
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.
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
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Lead sponsor
Wuxi No. 2 People's Hospital
Collaborator
Changzhou No.2 People's Hospital
Collaborator