A Study of Cadonilimab(AK104) Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma
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ClinicalTrials.gov Identifier: NCT06035224 |
Recruitment Status :
Recruiting
First Posted : September 13, 2023
Last Update Posted : September 13, 2023
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Condition or disease | Intervention/treatment | Phase |
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Clear Cell Renal Cell Carcinoma、Resistance to Immunotherapy | Drug: AK104(anti-PD-1/CTLA-4 bi-specific antibody ,intravenously),lenvatinib( targeted VEGFR 1-3、FGFR、PDGFRα, small molecule TKI,orally | Phase 2 |
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 : | Interventional (Clinical Trial) |
Estimated Enrollment : | 28 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | A Single Arm, Phase II Trial of Cadonilimab (AK104) Plus lenvatinib in Previous immunotherapy treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma (ccRCC) |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Single Arm, Phase II Trial of Cadonilimab (AK104) Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma (ccRCC) |
Actual Study Start Date : | August 23, 2023 |
Estimated Primary Completion Date : | August 31, 2025 |
Estimated Study Completion Date : | July 31, 2026 |
Arm | Intervention/treatment |
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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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Drug: AK104(anti-PD-1/CTLA-4 bi-specific antibody ,intravenously),lenvatinib( targeted VEGFR 1-3、FGFR、PDGFRα, small molecule TKI,orally
AK104 (10mg/kg ,Q3W,intravenously) plus lenvatinib(<60kg,8 mg qd;≥60kg,12mg qd, orally. |
- 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
- Duration of response (DOR) [ Time Frame: Up to 2 years ]Duration of response (DOR) assessed according to RECIST v1.1
- Disease control rate (DCR) [ Time Frame: Up to 2 years ]Disease control rate (DCR) assessed according to RECIST v1.1
- Time to response(TTR) [ Time Frame: Up to 2 years ]Time from randomization to obtaining clinical efficacy (CR/PR)
- 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).
- 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.
- 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
- HRQoL based on EORTC QLQ-C30 [ Time Frame: Up to 2 years ]
- HRQoL based on EORTC QLQ-H&N35. [ Time Frame: Up to 2 years ]
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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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;
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Is pregnant or breastfeeding, or expecting to conceive children duration of the trial.
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06035224
Contact: jiwei Huang, Dr | 8613651682825 | jiweihuang@outlook.com |
China, Shanghai | |
Shanghai Renji Hospital | Recruiting |
Shanghai, Shanghai, China, 200123 | |
Contact: jiwei huang 8621-68383544 jiweihuang@outlook.com |
Responsible Party: | RenJi Hospital |
ClinicalTrials.gov Identifier: | NCT06035224 |
Other Study ID Numbers: |
LY2023-132-A |
First Posted: | September 13, 2023 Key Record Dates |
Last Update Posted: | September 13, 2023 |
Last Verified: | September 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
AK104 Lenvatinib |
Carcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma 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 Lenvatinib Antibodies Antibodies, Bispecific Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |