Cadonilimab (AK104) Plus Lenvatinib in Previously Immunotherapy-Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma

NCT06035224 | Active Not Recruiting Phase 2

• 1 other identifier: CLEAR-IT
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, open-label, multicenter, single-arm study evaluating the efficacy and safety of cadonilimab (AK104) in combination with lenvatinib in patients with unresectable advanced or metastatic clear cell renal cell carcinoma (ccRCC) who experienced disease progression during or after prior first-line immunotherapy-based combination therapy. Patients receive cadonilimab plus lenvatinib until radiographic disease progression, unacceptable toxicity, withdrawal of consent, death, or investigator decision. The primary endpoint is objective response rate (ORR) according to RECIST version 1.1 as assessed by investigators.

Conditions

Clear Cell Renal Cell Carcinoma

Keywords

Clear cell renal cell carcinoma; Immunotherapy rechallenge; Tyrosine kinase inhibitor; PD-1/CTLA-4 bispecific antibody

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Proportion of participants achieving confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by investigators.

  Up to 2 years

Secondary Outcomes (6)

• Duration of response (DOR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Time to response（TTR）

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

Other Outcomes (2)

• Exploratory biomarker analyses of PD-L1 expression

  Up to 2 years

• Exploratory biomarker analyses of circulating tumor DNA (ctDNA)

  Up to 2 years

Study Arms (1)

AK104 combine with lenvatinib

EXPERIMENTAL

Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(\<60kg，8 mg qd；≥60kg，12mg qd, orally.

Drug: AK104（anti-PD-1/CTLA-4 bi-specific antibody ，intravenously）,lenvatinib（ targeted VEGFR 1-3、FGFR、PDGFRα， small molecule TKI，orally

Interventions

AK104（anti-PD-1/CTLA-4 bi-specific antibody ，intravenously）,lenvatinib（ targeted VEGFR 1-3、FGFR、PDGFRα， small molecule TKI，orally DRUG

AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(\<60kg，8 mg qd；≥60kg，12mg qd, orally.

AK104 combine with lenvatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent provided prior to study procedures.
• Age ≥18 and ≤80 years at the time of consent.
• Histologically or cytologically confirmed renal cell carcinoma with clear cell component.
• Unresectable locally advanced or metastatic disease.
• Radiographic disease progression during or after prior first-line immunotherapy-based combination therapy for advanced RCC.
• At least one measurable lesion according to RECIST v1.1.
• ECOG performance status of 0 or 1.
• Estimated life expectancy of at least 3 months.
• Adequate organ function, including hematologic, renal, hepatic, and coagulation parameters, as defined in the protocol.

You may not qualify if:

• History of hypersensitivity to monoclonal antibodies or any component of cadonilimab or lenvatinib.
• Known additional malignancy that is progressing or has required active treatment. Exceptions include adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ.
• Prior treatment with dual immune checkpoint blockade, defined as anti-PD-1/PD-L1 combined with anti-CTLA-4 therapy.
• Uncontrolled clinically significant cardiovascular disease or symptoms.
• Diagnosis of immunodeficiency or receipt of systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive therapy within 14 days prior to first dose.
• Active autoimmune disease or history of autoimmune disease that may worsen with immunostimulatory therapy. Subjects with type 1 diabetes mellitus, vitiligo, psoriasis, or hypo-/hyperthyroidism not requiring immunosuppressive treatment are eligible.
• History of non-infectious pneumonitis requiring steroids or current pneumonitis/interstitial lung disease.
• Active tuberculosis or active syphilitic infection.
• Known history of human immunodeficiency virus (HIV) infection.
• Active hepatitis B infection (HBsAg positive with HBV DNA \>500 IU/mL) or active hepatitis C infection (detectable HCV RNA).
• Clinically significant toxicities from prior anticancer therapy not recovered to Grade ≤1 (except alopecia or stable endocrinopathies).
• Active bleeding disorder or history of clinically significant bleeding episodes.
• Drug abuse, psychiatric illness, or medical/social conditions that may interfere with study participation or evaluation of results.
• Pregnant or breastfeeding women, or participants planning conception during the study treatment period.

Sponsors & Collaborators

• RenJi Hospital: lead
• Ruijin Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator

Study Sites (1)

Shanghai Renji Hospital

Shanghai, Shanghai Municipality, 200123, China

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients receive oral lenvatinib at a starting dose of: 8 mg once daily for body weight \<60 kg 12 mg once daily for body weight ≥60 kg Cadonilimab (AK104) is administered intravenously at 10 mg/kg every 3 weeks. Treatment continues until radiographic disease progression, unacceptable toxicity, withdrawal of informed consent, initiation of new anticancer therapy, death, loss to follow-up, or investigator decision.

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 13, 2023
• Study Start: August 23, 2023
• Primary Completion: January 12, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)