Unresectable or Advanced Clear Cell Renal Cell Carcinoma That Has Progressed After Previous Immunotherapy
Conditions
Keywords
JS004, Toripalimab, ccRCC, immunotherapy
Brief summary
This study is A prospective，single arm, multicenter clinical study of BTLA monoclonal antibody JS004 (B/T lymphocyte attenuator factor monoclonal antibody) in combination with toripalimab in patients with unresectable or advanced renal cell carcinoma who had failed previous immunotherapy Subjects will receive JS004（B/T lymphocyte attenuator factor monoclonal antibody） plus Toripalimab until disease progression, development of unacceptable toxic effects, death, a decision by the physician or patient to withdraw from the trial. The primary endpoint is ORR per RECIST v1.1 as assessed by investigators(continuous treatment for up to 2 years).
Interventions
DRUGJS004（BTLA monoclonal antibody，intravenously）,Toripalimab（ anti-PD-1specific antibody，intravenously)
Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection 200mg via IV infusion once every 3 weeks Toripalimab 240mg via IV infusion once every 3 weeks JS004 will be administered in combination with toripalimab until disease progression or intolerable toxicity or up to 2 years of treatment or other reasons specified in the protocol
Sponsors
RenJi Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Have fully understood and voluntarily signed the Informed Consent Form (ICF); 2. 18-75 years old (at the time of signing the informed consent form); No gender restrictions; ECOG PS score: 0-1 points; 3. Renal cell carcinoma with clear cell components confirmed by histology or cell pathology, including metastatic renal cell carcinoma mainly composed of clear cell components; 4. Previous treatment history of the subject: Patients who have received 1-2 systemic treatments containing immunotherapy and have experienced disease progression or intolerance; 5. Confirm the presence of at least one measurable lesion according to RECIST 1.1 criteria; 6. Agree to provide sufficient previously stored tumor tissue specimens or agree to undergo biopsy Collect tumor tissue for PD-L1, CD8 expression level determination, and MSI, TMB, KRAS, BRAF, PIK3CA, NRAS, PTEN, EGFR, HER2, HRAS, KIT, MET, ROS1, POLE, POLD1, TP53 gene mutation detection; 7. The main organ functions well and meets the following standards: 1. Blood routine examination standards (corrected for no blood transfusion or use of hematopoietic stimulating factor drugs within 2 weeks before the first trial medication): 1. Hemoglobin (HGB) ≥ 90g/L; 2. Absolute neutrophil count (NEUT) ≥ 1.5 × 109/L; 3. Platelet count (PLT) ≥ 100 × 109/L. 2. Biochemical tests must meet the following standards: 1. Serum total bilirubin (TBIL) ≤ 1.5 × ULN or direct bilirubin ≤ 1.0 × ULN; 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. If accompanied by liver metastasis, ALT and AST should be ≤ 5 × ULN; 3. Serum creatinine (CR) ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60ml/min 3. Coagulation function test: Activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN, unless the subject is receiving anticoagulant therapy and coagulation parameters (PT/INR and APTT) are within the expected range of anticoagulant therapy at screening; 4. Left ventricular ejection fraction (LVEF) ≥ 50%; 5. Endocrine function: Normal thyroid stimulating hormone (TSH), or abnormal TSH but normal FT3 and FT4; 8. Willing and able to comply with the research plan's visits, treatment laboratory tests, sample collection, and other procedures; 9. Female patients with fertility must voluntarily adopt efficient contraceptive measures (such as oral contraception, injection contraception, or implanted barrier contraception, spermicides and condoms, or intrauterine devices) for at least 120 days from the last dose during the study period, and have negative urine or serum pregnancy test results ≤ 7 days before enrollment; 10. Male patients who have not been sterilized must voluntarily adopt effective contraceptive measures for at least 120 days from the last dose during the study period.
Exclusion criteria
Participants who meet any of the following criteria will not be allowed to enter this study: 1. History of malignant tumors other than the research disease within the past 5 years, except for malignant tumors that can be expected to recover after treatment (including but not limited to fully treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell carcinoma, or radical surgery for ductal carcinoma in situ); 2. Four weeks before the first study medication, receive systemic treatment with other anti-tumor drugs (if it has a half-life of five, it can be included in the group), or receive local anti-tumor treatment, or receive clinical investigational drug or device treatment; 3. Received immunotherapy within 4 weeks prior to the first study medication; 4. Have undergone major surgery (as determined by the investigator) or are in the recovery period within 4 weeks prior to the first trial administration; 5. Patients who have previously received treatment with anti BTLA or anti HVEM antibodies; 6. Have a history of severe drug allergies, including but not limited to antibody drugs; 7. Patients with contraindications for immunotherapy restart: a) grade 2-4 immune myocarditis; b) Severe grade 4 proteinuria; c) Severe or life-threatening grade 4 immune hepatitis; d) Severe grade 3-4 immune pneumonia; e) Severe inflammatory arthritis that significantly affects daily life or quality of life; f) Severe neurological toxicity: grade 2-4 myasthenia gravis; Any level of Guillain Barr é syndrome (GBS) or transverse myelitis; Grade 2-4 encephalitis; g) Severe or life-threatening grade 3-4 pancreatitis; h) Serious or life-threatening bullous diseases (grades 3-4); i) Severe grade 3-4 uveitis or episcleritis; 8. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation, or requiring long-term treatment with corticosteroids; 9. Only hypothyroidism, suprarenal or pituitary dysfunction that can be controlled by hormone replacement therapy, type I diabetes, psoriasis or vitiligo that does not need systematic treatment can participate in this study; 10. The toxicity has not improved after previous anti-tumor treatment, that is, it has regressed to baseline, NCI-CTCAE 5.0 grade 0-1 (except for hair loss), or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR per RECIST v1.1 as assessed by investigators | Up to 2 years | ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 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). |
| Disease control rate (DCR) | Up to 2 years | Disease control rate (DCR) assessed according to RECIST v1.1 |
| Overall survival (OS) | Up to 2 years | Overall survival is defined as the time from the start of treatment until death due to any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | Up to 2 years | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree |
Countries
China
Contacts
Primary ContactJiwei Huang, Dr
Outcome results
None listed