An Exploratory Clinical Study to Evaluate the Safety, Feasibility, and Preliminary Efficacy of Intratumoral Delivery of CA9-Targeted Chimeric Antigen Receptor Macrophage Therapy in Patients With Unresectable or Metastatic Clear Cell Renal Cell Carcinoma
| Registry | NCT07865832, acronym CM-BA-9 |
|---|---|
| Status | Not yet recruiting |
| Phase | Early Phase 1 |
| Study type | Interventional; na, single group, masking: none, treatment |
| Enrollment | 6 (Estimated) |
| Sponsor | Liangyou Gu (Other) |
| Conditions | Clear Cell Renal Cell Carcinoma |
| Interventions | CM-BA-9 (Biological) |
| Dates | start 2026-11-01 (estimated), primary completion 2028-09-01 (estimated), completion 2029-09-01 (estimated), first posted 2026-10-08, last updated 2026-10-08 |
| Locations | 1 site in China |
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All trials for Clear Cell Renal Cell Carcinoma All trials of CM-BA-9
Clear cell renal cell carcinoma is the most common type of kidney cancer. Although new treatments such as immune checkpoint inhibitors and targeted therapies have improved outcomes for many patients, some patients with advanced disease may still experience disease progression and require new treatment approaches. This study evaluates the safety, feasibility, and preliminary effectiveness of a novel cell therapy called CA9-targeted chimeric antigen receptor macrophage (CAR-M) therapy in patients with unresectable or metastatic clear cell renal cell carcinoma. CA9 is a protein that is highly expressed on many clear cell renal cell carcinoma cells and can be recognized by CAR-M cells. In this study, patients will receive a local injection of CM-BA-9, a CA9-targeted CAR-M cell product, into selected tumor lesions. The study will primarily assess treatment safety and tolerability, while also exploring whether this therapy can control tumor growth. The information collected in this study may help researchers better understand the potential role of CAR-M therapy in the treatment of advanced clear cell renal cell carcinoma.
Clear cell renal cell carcinoma (ccRCC) represents the predominant histological subtype of renal cell carcinoma and is characterized by frequent alterations in the tumor microenvironment, including immune suppression and abnormal angiogenesis. Despite advances in immune checkpoint inhibitors and targeted therapies, patients with unresectable or metastatic ccRCC may develop resistance and have limited treatment options. Carbonic anhydrase IX (CA9) is a tumor-associated antigen highly expressed in most ccRCC tumors with limited expression in normal tissues, making it a potential therapeutic target. Chimeric antigen receptor macrophage (CAR-M) therapy is an emerging cellular immunotherapy strategy designed to enhance macrophage-mediated recognition and elimination of tumor cells. This exploratory clinical study is designed to evaluate the safety, feasibility, and preliminary efficacy of intratumoral delivery of CM-BA-9, a CA9-targeted CAR-M cell therapy product, in patients with unresectable or metastatic ccRCC. The study will evaluate treatment-related adverse events, dose-limiting toxicities, feasibility of product administration, and preliminary antitumor activity. The findings from this study will provide preliminary clinical evidence regarding the safety profile and potential therapeutic value of CA9-targeted CAR-M therapy and may support further investigation of cellular immunotherapy approaches for advanced ccRCC.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| CM-BA-9 Sequential Dose Exploration Cohort | Experimental | Biological: CM-BA-9 | Participants will receive a single ultrasound-guided intratumoral injection of CM-BA-9. After completion of protocol-defined safety monitoring, subsequent anticancer therapies, including targeted therapy or immune checkpoint inhibitor-based therapy, may be administered according to investigator assessment. |
Sex: All, ages: 18 Years to 75 Years
Inclusion Criteria: * 1\. Male or female participants aged 18 to 75 years. * 2\. Histologically confirmed clear cell renal cell carcinoma (ccRCC). * 3\. Unresectable locally advanced or metastatic renal cell carcinoma. * 4\. Participants with advanced disease who require later-line systemic treatment following progression on prior standard anticancer therapy, as determined by the investigator. * 5\. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. * 6\. At least one tumor lesion suitable for ultrasound-guided intratumoral injection, including a primary renal tumor, residual renal lesion, or locoregionally recurrent lesion in the renal region. * 7\. Evidence of CA9 expression in the lesion intended for injection or a representative tumor lesion, as determined according to protocol-defined criteria. * 8\. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * 9\. Life expectancy of at least 12 weeks. * 10\. Adequate bone marrow function, defined as an absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, and hemoglobin (Hb) ≥90 g/L, and meeting the requirements for peripheral blood mononuclear cell (PBMC) collection. * 11\. Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × the upper limit of normal (ULN), or ≤5 × ULN in the presence of liver metastases, and total bilirubin ≤1.5 × ULN. * 12\. Adequate renal function, defined as estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m² or serum creatinine ≤1.5 × ULN. * 13\. Adequate coagulation function for tumor puncture and intratumoral injection, defined as international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 × ULN. * 14\. Considered by the investigator to be able to tolerate filgrastim mobilization, PBMC collection, and subsequent cellular therapy procedures. * 15\. Screening for hepatitis B, hepatitis C, human immunodeficiency virus (HIV), and syphilis meeting protocol-defined requirements. * 16\. Considered by the investigator to be able to tolerate ultrasound-guided tumor puncture and intratumoral injection. * 17\. Voluntary participation in the study and provision of written informed consent before initiation of any study-related procedures. Exclusion Criteria: * 1\. Life expectancy of less than 3 months. * 2\. History of or concurrent active malignancy, except for cervical carcinoma in situ that has been cured or remained recurrence-free for at least 3 years, noninvasive basal cell or squamous cell carcinoma of the skin, ductal carcinoma in situ after curative resection, or localized prostate cancer with no evidence of recurrence after definitive treatment. * 3\. Prior treatment with CA9-targeted cellular therapy, or other CA9-targeted therapy that, in the investigator's judgment, may interfere with the safety or efficacy assessments of this study. * 4\. Prior treatment with CAR-T, CAR-NK, CAR-M, or other genetically engineered cellular therapy. * 5\. History of clinically significant central nervous system disease or dysfunction, including but not limited to stroke, intracranial hemorrhage, epilepsy, dementia, cerebellar disease, or aphasia; or active central nervous system metastases with associated symptoms. * 6\. History of solid organ transplantation (e.g., heart, lung, liver, or kidney) or hematopoietic stem cell/bone marrow transplantation. * 7\. Myocardial infarction, percutaneous coronary intervention, coronary stent placement, unstable angina, or other clinically significant severe cardiovascular disease within 12 months before screening. * 8\. Toxicities related to prior anticancer therapy that have not recovered to Grade ≤1 according to CTCAE v5.0, except for alopecia, stable endocrine abnormalities, or other toxicities considered by the investigator not to pose a safety risk. * 9\. Prior anticancer therapy for which the protocol-specified washout period has not been completed, or for which fewer than 5 half-lives of the respective treatment have elapsed before study treatment. * 10\. Uncontrolled active bacterial, viral, fungal, or other pathogenic infection, or other infectious disease considered by the investigator to preclude participation in the study. * 11\. Positive human immunodeficiency virus (HIV) antibody; untreated syphilis with positive Treponema pallidum antibody; hepatitis B surface antigen (HBsAg) positivity with detectable HBV DNA; or detectable hepatitis C virus (HCV) RNA. Participants whose infection can be adequately controlled with prophylactic or therapeutic medication, as determined by the investigator, may be eligible. * 12\. Known active autoimmune disease requiring systemic treatment, or a history of severe autoimmune disease considered by the investigator to confer a high risk associated with study treatment. * 13\. History of severe hypersensitivity to filgrastim, the cellular product, any medication used during the study, or any of their components. * 14\. Pregnant or breastfeeding women; participants of childbearing potential and their partners who are unwilling to use effective contraception during the study. * 15\. Participation in another interventional clinical study with receipt of investigational treatment within 3 months before signing informed consent, or planned participation in another clinical study during the study period. * 16\. Depression, suicidal ideation, psychiatric disorder, or other psychological or psychiatric condition that may adversely affect study compliance or safety. * 17\. Uncontrolled systemic inflammatory disease, a history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), or a condition considered by the investigator to confer a high risk of cytokine storm. * 18\. Clinically significant coagulation abnormality, bleeding tendency, or inability to discontinue anticoagulant or antiplatelet therapy, including but not limited to INR >1.5, APTT >1.5 × the upper limit of normal (ULN), or platelet count <75 × 10⁹/L. * 19\. End-stage renal disease, dialysis dependence, or severe renal impairment considered by the investigator to preclude safe intratumoral injection. * 20\. Unsuitability for ultrasound-guided intratumoral injection based on imaging assessment, including but not limited to inability to establish a safe puncture route, proximity of the target lesion to major blood vessels or vital organs, high bleeding risk, or a lesion location that cannot be safely accessed. * 21\. Inability, as determined by the investigator, to tolerate filgrastim mobilization, PBMC collection, cell manufacturing, or subsequent cellular therapy procedures. * 22\. Any disease, laboratory abnormality, or social circumstance that may interfere with safety or efficacy assessments or the participant's ability to complete the study. * 23\. Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.
| Facility | City | Country | Status |
|---|---|---|---|
| Chinese People's Liberation Army General Hospital | Beijing, Beijing Municipality | China |