Cadonilimab Combination With Lenvatinib as Neoadjuvant Therapy for ccRCC

A Single-Arm Phase II Clinical Study Evaluating the Efficacy and Safety of Cadonilimab Combined With Lenvatinib as Neoadjuvant Therapy in Renal Cell Carcinoma Patients With Partial Nephrectomy Indications But High Surgical Risk

Through the neoadjuvant treatment with a combination of Cadonilimab and Lenvatinib, it enabled the successful and safe implementation of partial nephrectomy in patients with localized renal cancer, who had indications for nephron-sparing surgery but faced considerable difficulty in preserving the kidney (tumors measuring 4-7 cm located at the renal hilum or with endophytic growth ≥75% or tumors >7 cm)

Inclusion Criteria:

1. Voluntary provision of written informed consent prior to any study-related procedures.

2. Age ≥18 years at the time of enrollment; no restriction on sex.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

4. Estimated survival ≥3 months.

5. Pathological confirmation of clear cell RCC or predominantly clear cell renal cell carcinoma by preoperative needle biopsy.

6. Patient willingness to undergo nephron-sparing surgery.

7. Presence of indications for nephron-sparing surgery but with high surgical complexity: 1) tumors measuring 4-7 cm located at the renal hilum or with endophytic growth ≥75%; or 2) tumors >7 cm.

8. At least one measurable lesion per RECIST v1.1 criteria, suitable for repeated accurate measurement.

9. Adequate organ function, with laboratory results during the screening period meeting all of the following criteria:

   Hematology (no blood component or colony-stimulating factor support permitted within 2 weeks prior to treatment initiation):

   • Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (≥1,500/mm³)
   • Platelet count (PLT) ≥100 × 10⁹/L (≥100,000/mm³)
   • Hemoglobin (Hb) ≥90 g/L

   Hepatic function:

   • Serum total bilirubin (TBIL) ≤1.5 × ULN
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN
   • Serum albumin (ALB) ≥28 g/L

   Coagulation:

   - International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 × ULN

10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory assessments, and all other study requirements.

Exclusion Criteria:

Patients meeting any of the following criteria will be ineligible for participation:

1. Lymph node metastasis
2. Tumor encasing the renal artery
3. Tumor thrombus within the renal vein
4. Diffuse tumor growth without a clear boundary with normal renal parenchyma
5. Poor general condition precluding tolerance of general anesthesia based on anesthesiological assessment
6. Severe cardiovascular or cerebrovascular disease, uncontrolled hypertension, or uncontrolled diabetes mellitus
7. Long-term use of immunosuppressive agents following organ transplantation
8. Current use of immunosuppressive medications
9. Active or clinically apparent infection or fever
10. T-cell lymphoma or multiple myeloma
11. Concurrent other malignancies, currently undergoing treatment for other benign or malignant tumors, or a history of other malignancies within the preceding 6 months
12. Metastatic renal cell carcinoma
13. Receipt of traditional Chinese herbal medicines with antitumor indications or immunomodulatory agents within 14 days prior to the first dose of study drug
14. Ongoing systemic therapy (including thymosin, interferon, or interleukins; local use for control of pleural effusion is permitted)
15. Active or potentially relapsing autoimmune disease; the following conditions are exempt: vitiligo, alopecia, psoriasis, or eczema not requiring systemic treatment; hypothyroidism secondary to autoimmune thyroiditis requiring only stable-dose hormone replacement therapy; type 1 diabetes mellitus requiring only stable-dose insulin replacement therapy
16. Concurrent enrollment in another clinical study, unless it is an observational/non-interventional study or the follow-up phase of an interventional study
17. Known history of psychiatric illness, substance abuse, alcohol dependence, or illicit drug use
18. Pregnant or breastfeeding women
19. Any concurrent disease, prior treatment, or laboratory abnormality that may confound study results, interfere with the subject's full study participation, or indicate that participation may not be in the subject's best interest