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.
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.
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.
Single group
CM-BA-9
Biological/VaccineCM-BA-9 is an autologous CA9-targeted chimeric antigen receptor macrophage (CAR-M) cell product. After peripheral blood mononuclear cell collection and manufacturing, CM-BA-9 will be administered as a single ultrasound-guided intratumoral injection.
Safety and tolerability of CM-BA-9
Safety and tolerability will be assessed based on the incidence and severity of dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and intratumoral injection-related complications. DLTs will be assessed during the 28-day DLT evaluation period. Safety events will be evaluated throughout the study according to the protocol-defined criteria.
Feasibility of CM-BA-9 manufacturing and administration
Feasibility will be assessed based on successful completion of peripheral blood mononuclear cell (PBMC) collection, cell manufacturing and product release, preparation for administration, intratumoral administration, and the overall treatment process according to the study protocol.
Objective response rate (ORR)
The proportion of participants achieving a best overall response of complete response (CR) or partial response (PR), as assessed according to RECIST v1.1.
Disease control rate (DCR)
The proportion of participants achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed according to RECIST v1.1.
Duration of response (DoR)
Duration of response will be assessed among participants achieving CR or PR and defined as the time from the first documented objective response to disease progression or death, whichever occurs first.
Progression-free survival (PFS)
Progression-free survival will be defined as the time from CM-BA-9 administration to disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Persistence of CA9-CAR-related sequences after CM-BA-9 treatment
The persistence of CA9-CAR-related sequences, including CAR DNA/circular RNA-related signals, in peripheral blood after CM-BA-9 administration will be evaluated.
Change in CAR expression level after CM-BA-9 administration
CAR expression levels after CM-BA-9 administration will be assessed at different time points to characterize changes in CAR expression over time.
Changes in immune microenvironment after CM-BA-9 treatment
Changes in immune cell populations, including T cells, B cells, NK cells, monocytes/macrophages, and immune-related biomarkers in peripheral blood and tumor samples after CM-BA-9 administration will be explored.
Changes in serum cytokine profiles after CM-BA-9 treatment
Changes in serum cytokine levels, including IL-2, IL-6, IL-10, TNF-α, IFN-γ, and other relevant inflammatory or immune-related cytokines, will be evaluated after CM-BA-9 administration to characterize immune activation and treatment-related biological changes.
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Liangyou Gu
Lead sponsor
Chinese PLA General Hospital
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
