- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06035224
A Study of Cadonilimab(AK104) Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma
A Single Arm, Phase II Trial of Cadonilimab (AK104) Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)
Study Overview
Status
Detailed Description
This trial is a single-arm, multicenter clinical study with the aim of enrolling 28 patients with unresectable advanced ccRCC. The study was divided into three research centers, namely Renji Hospital Affiliated to Shanghai Jiao Tong University, Zhongshan Hospital Affiliated to Fudan University in Shanghai, and Shanghai Ruijin Hospital. Lenvatinib capsules are taken orally, 8 mg once daily (qd) for subjects weighing < 60 kg, 12 mg once daily (qd) for subjects weighing ≥ 60 kg, combined with cardunilimab, intravenous infusion, 10 mg/kg, once every three weeks (q3w) until disease progression, death, intolerable toxicity, withdrawal of informed consent, initiation of new antitumor therapy, investigator decision, loss to follow-up, whichever occurs first. Tumor efficacy will be assessed at baseline, every 6 weeks (6 weeks ± 7 days) during treatment, and at end-of-treatment visits.
The experiment is mainly divided into the effectiveness import stage and the cohort expansion stage. The safety introduction phase planned to enroll 12 patients, and after the first dose, the dosing regimen: lenvatinib capsules orally, 8 mg once daily (qd) for subjects weighing < 60 kg, 12 mg once daily (qd) for subjects weighing ≥ 60 kg, in combination with cartunilimab, intravenous infusion, 10 mg/kg every three weeks (q3w), evaluated in 12 patients, 2 or more patients achieved remission before cohort expansion.
The cohort expansion phase plans to enroll 16 patients with accRCC with lenvatinib capsules orally 8 mg once daily (qd) for subjects weighing < 60 kg, 12 mg once daily (qd) for subjects weighing ≥ 60 kg, plus cardunilimab, intravenous infusion, 10 mg/kg every three weeks (q3w) until disease progression, intolerable toxicity, withdrawal of informed consent, loss to follow-up or death, The investigator or subject decided to terminate the treatment, or the study ended the capsules used in this study were donated by Jiangsu Simcere Zaiming Pharmaceutical Co., Ltd., and cardunilimab was donated by Akeso.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jiwei Huang, Dr
- Phone Number: 8613651682825
- Email: jiweihuang@outlook.com
Study Locations
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Shanghai
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Shanghai, Shanghai, China, 200123
- Recruiting
- Shanghai Renji Hospital
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Contact:
- jiwei huang
- Phone Number: 8621-68383544
- Email: jiweihuang@outlook.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Provide written informed consent/assent for the trial.
- Be ≥18 and ≤ 75 years of age on day of signing informed consent. 3)Have histologically or cytologically confirmed diagnosis of RCC with advanced/metastatic disease with clear cell component.
4)Have previous immunotherapy combined treatment progression( only second line systemic therapy for advanced RCC included) 5)Have measurable disease per RECIST 1.1 as assessed by the investigator /site radiologist.
6)Have estimated life expectancy of at least 3 months. 7)Have ECOG PS 0-1. 8)Hematology: i. absolute neutrophil count (ANC) ≥ 1.5 × 109/L ; ii. platelets ≥ 100 × 109/L ; iii. hemoglobin ≥ 90 g/L.
9)Renal: i. calculated creatinine clearance * (CrCl) ≥ 60 mL/min; * CrCl will be calculated using the Cockcroft-Gault formula CrCL (mL/min) = {(140-age) × body weight (kg) × F }/(SCr (mg/dL) × 72) ii. urine protein < 2 + or 24-hour urine protein must be < 2.0 g.
10)Hepatic: i. serum total bilirubin (TBil) ≤ 1.5 × ULN; ii. AST and ALT ≤ 3 × ULN, ≤ 5 × ULN with liver metastasis; iii. serum albumin (ALB) ≥ 28 g/L.
11)Coagulation function: i. international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
Exclusion Criteria:
- Has history of allergies to monoclonal antibodies, any components of cadonilimab and lenvatinib
- Has a known additional malignancy that has progressed or has required active treatment. Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or carcinoma in situ are not excluded.
- Has prior Dual immunotherapy treatment (any anti-PD-1/PD-L1 combined with anti-CLTA-4 ).
- Has Uncontrolled clinical symptoms or diseases of the heart
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days (prednisone>10 mg/day or equivalent dose)
- Has active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Subjects with diabetes type I, vitiligo, psoriasis, hypo-or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has an active tuberculosis and syphilitic infection.
- Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV antibodies).
- Has known active Hepatitis B (e.g., Hepatitis B surface antigen [HBsAg] reactive and HBV-DNA>500 IU/ml) or Hepatitis C virus (e.g., HCV RNA [qualitative] is detected).
- Has never recovered from previous anti-tumor treatment toxicity
- Has active bleeding disorder or other history of significant bleeding episodes .
- drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results;
Is pregnant or breastfeeding, or expecting to conceive children duration of the trial.
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AK104 combine with lenvatinib
Patients will receive AK104 (10mg/kg ,Q3W,intravenously) plus lenvatinib(<60kg,8 mg qd;≥60kg,12mg qd, orally.
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AK104 (10mg/kg ,Q3W,intravenously) plus lenvatinib(<60kg,8 mg qd;≥60kg,12mg qd, orally.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ORR per RECIST v1.1 as assessed by investigators
Time Frame: Up to 2 years
|
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Up to 2 years
|
Overall survival is defined as the time from the start of treatment until death due to any cause.
|
Up to 2 years
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Duration of response (DOR)
Time Frame: Up to 2 years
|
Duration of response (DOR) assessed according to RECIST v1.1
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Up to 2 years
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Disease control rate (DCR)
Time Frame: Up to 2 years
|
Disease control rate (DCR) assessed according to RECIST v1.1
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Up to 2 years
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Progression-free survival (PFS)
Time Frame: Up to 2 years
|
PFS is defined as the time from the the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
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Up to 2 years
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Time to response(TTR)
Time Frame: Up to 2 years
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Time from randomization to obtaining clinical efficacy (CR/PR)
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Up to 2 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Event
Time Frame: Up to 2 years
|
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree
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Up to 2 years
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HRQoL based on EORTC QLQ-C30
Time Frame: Up to 2 years
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Up to 2 years
|
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HRQoL based on EORTC QLQ-H&N35.
Time Frame: Up to 2 years
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Carcinoma, Renal Cell
- Carcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Antibodies
- Lenvatinib
- Antibodies, Bispecific
Other Study ID Numbers
- LY2023-132-A
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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