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)

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Cadonilimab Combined With Lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Other (Non U.s.)
    • Guangzhou, Other (Non U.s.), China, 0755
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab combined with Lenvatinib as neoadjuvant therapy	Drug: Cadonilimab Combined With Lenvatinib; Lenvatinib Treatment Lenvatinib (8mg [body weight < 60 kg] or 12 mg [body weight ≥ 60 kg]) orally once daily, with or without food.; Intravenous Infusion of Cadonilimab (Injection) Infuse Cadonilimab at a dose of 6mg/kg intravenously every two weeks, constituting one treatment cycle, a total of 3 or 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate (ORR) based on RECIST 1.1 criteria.	Evaluation at the end of Cycle 3 or 6 (each cycle is 14 days) of Cadonilimab treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response rate (MPR)	The proportion of patients with residual viable tumor cells in tumor specimens and lymph nodes resected after neoadjuvant therapy, which are ≤10%.	The evaluation was conducted 5 days after surgery.
Nephron-sparing surgery (NSS) success rate	The success rate of all enrolled patients undergoing partial nephrectomy.	Evaluation at the end of surgery.
R0 resection rate	R0 resection rate refers to the percentage of patients in whom a tumor is surgically removed with no microscopic residual disease. Specifically, it means that after pathological examination of the resected specimen, the tumor margins are negative (no cancer cells are found at the cut edge).	The evaluation was conducted 5 days after surgery.
Surgical complication rate	Surgical complication rate is the proportion of patients who experience any unintended, adverse event (such as infection, bleeding, organ injury, or anastomotic leak) following a surgical procedure	From the end of surgery to three months after surgery
Drug safety profile	Incidence and severity of adverse events during the use of Cadonilimab and Lenvatinib.	During the treatment of combination of Cadonilimab and Lenvatinib.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): December 9, 2024
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; Clear Cell Renal Cell Carcinoma; Cadonilimab
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; lenvatinib
• Other Study ID Numbers: 2023-FXY-117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No