Not yet recruitingNCT07865832CM-BA-9Updated Oct 8, 2026

A Study of CA9-Targeted CAR Macrophage Therapy in Advanced Clear Cell Renal Cell Carcinoma

An Early Phase 1 interventional study of CM-BA-9 in Clear Cell Renal Cell Carcinoma, sponsored by Liangyou Gu. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-10-08.

Sponsored by Liangyou Gu · Early Phase 1, Interventional, and Treatment

Updated Oct 8, 2026Newly registeredGo to Updates ↓

Phase: Early Phase 1
Study type: Interventional
Enrollment: 6
Allocation: Not applicable
Ages: 18 Years to 75 Years
Sex: All

Study summary

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.

Read the detailed description

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.

Conditions studied

Clear Cell Renal Cell Carcinoma

Browse trials for

Carcinoma, Renal Cell 1,965

Keywords

CA9
Chimeric Antigen Receptor Macrophage
CAR-M
Cell Therapy
CM-BA-9
Advanced Clear Cell Renal Cell Carcinoma

In context

Carcinoma, Renal Cell

1,965 studies on the registry are indexed under Carcinoma, Renal Cell; 378 are open to participants now.

This study's planned enrollment of 6 is below the median of 42 across 1,480 interventional studies indexed under Carcinoma, Renal Cell.

Browse Carcinoma, Renal Cell studies →

Lead sponsor

This is the only study on the registry with Liangyou Gu as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 6 participants (estimated)

Study arms

Experimental
CM-BA-9 Sequential Dose Exploration Cohort
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.
Biological: CM-BA-9

Interventions

BiologicalCM-BA-9
CM-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.

What researchers measure

Primary outcomes

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.
Time frame: From CM-BA-9 administration through 52 weeks after treatment
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.
Time frame: Within 3 weeks before CM-BA-9 administration

Secondary outcomes

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.
Time frame: Within 52 weeks after CM-BA-9 administration
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.
Time frame: Within 52 weeks after CM-BA-9 administration
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.
Time frame: From first documented CR or PR to disease progression or death, up to 52 weeks after CM-BA-9 administration
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.
Time frame: From CM-BA-9 administration to disease progression or death, up to 52 weeks
Overall survival (OS)
Overall survival will be defined as the time from CM-BA-9 administration to death from any cause.
Time frame: From CM-BA-9 administration to death from any cause, up to 52 weeks
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Scale
Changes in Eastern Cooperative Oncology Group (ECOG) performance status and clinical symptoms after CM-BA-9 administration will be evaluated during follow-up. ECOG performance status will be assessed using the ECOG Performance Status Scale, ranging from 0 to 5, with higher scores indicating greater functional impairment.
Time frame: Baseline and follow-up visits through 52 weeks after CM-BA-9 administration

Other outcomes

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.
Time frame: Baseline and within 4 weeks after CM-BA-9 administration
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.
Time frame: Baseline and within 4 weeks after CM-BA-9 administration
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.
Time frame: Baseline and within 52 weeks after CM-BA-9 administration
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.
Time frame: Baseline and within 52 weeks after CM-BA-9 administration
Changes in CA9 PET/CT imaging parameters after CM-BA-9 treatment
CA9 PET/CT imaging parameters, including tracer uptake and imaging characteristics, will be evaluated after CM-BA-9 administration and explored for associations with treatment response and safety outcomes.
Time frame: Baseline and within 52 weeks after CM-BA-9 administration
Correlation between CA9 PET/CT uptake parameters and tumor response
The correlation between CA9 PET/CT uptake parameters and tumor response assessed according to RECIST v1.1 after CM-BA-9 administration will be explored.
Time frame: Baseline and within 52 weeks after CM-BA-9 administration

Study locations

1 site

Chinese People's Liberation Army General Hospital
Beijing, Beijing Municipality 100853, China
- Liangyou Gu · Contact · guliangyouyd1@126.com · +86 010 6693 7166
- Liangyou Gu · Principal investigator

References and documents

Publications

Jing W, Han M, Wang G, Kong Z, Zhao X, Fu Z, Jiang X, Shi C, Chen C, Zhang J, Zheng Z, Gao J, Sun W, Tang C, Yang Z, Wang Y, Liu Y, Zhao K, Zhu D, Shi B, Jiang X. An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma. Nat Cancer. 2025 May;6(5):838-853. doi: 10.1038/s43018-025-00950-1. Epub 2025 Apr 29. PubMed 40301655 ↗
Duan Z, Li Z, Wang Z, Chen C, Luo Y. Chimeric antigen receptor macrophages activated through TLR4 or IFN-gamma receptors suppress breast cancer growth by targeting VEGFR2. Cancer Immunol Immunother. 2023 Oct;72(10):3243-3257. doi: 10.1007/s00262-023-03490-8. Epub 2023 Jul 12. PubMed 37438548 ↗
Cai J, Liu Z, Chen S, Zhang J, Li H, Wang X, Yang F, Wang S, Li X, Li Y, Chen K, Wang J, Sun M, Qiu M. Engineered circular RNA-based DLL3-targeted CAR-T therapy for small cell lung cancer. Exp Hematol Oncol. 2025 Mar 12;14(1):35. doi: 10.1186/s40164-025-00625-8. PubMed 40075480 ↗
Hu Q, Zhao H, Zhou K, Tian X, Wang Q, Hua X, Zhang X. Scarless circular mRNA-based CAR-T cell therapy elicits superior antitumor efficacy. Signal Transduct Target Ther. 2025 Dec 23;10(1):411. doi: 10.1038/s41392-025-02512-4. PubMed 41430032 ↗
Reiss KA, Angelos MG, Dees EC, Yuan Y, Ueno NT, Pohlmann PR, Johnson ML, Chao J, Shestova O, Serody JS, Schmierer M, Kremp M, Ball M, Qureshi R, Schott BH, Sonawane P, DeLong SC, Christiano M, Swaby RF, Abramson S, Locke K, Barton D, Kennedy E, Gill S, Cushing D, Klichinsky M, Condamine T, Abdou Y. CAR-macrophage therapy for HER2-overexpressing advanced solid tumors: a phase 1 trial. Nat Med. 2025 Apr;31(4):1171-1182. doi: 10.1038/s41591-025-03495-z. Epub 2025 Feb 7. PubMed 39920391 ↗
Klichinsky M, Ruella M, Shestova O, Lu XM, Best A, Zeeman M, Schmierer M, Gabrusiewicz K, Anderson NR, Petty NE, Cummins KD, Shen F, Shan X, Veliz K, Blouch K, Yashiro-Ohtani Y, Kenderian SS, Kim MY, O'Connor RS, Wallace SR, Kozlowski MS, Marchione DM, Shestov M, Garcia BA, June CH, Gill S. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol. 2020 Aug;38(8):947-953. doi: 10.1038/s41587-020-0462-y. Epub 2020 Mar 23. PubMed 32361713 ↗
Mueller KP, Grenier JM, Weber EW. CAR T cell persistence in cancer. Trends Cancer. 2025 Oct;11(10):1005-1018. doi: 10.1016/j.trecan.2025.08.014. Epub 2025 Sep 18. PubMed 40973578 ↗
Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, Scott AM, van Praet C, Bailly C, Onal B, Aksoy T, Merkx R, Schuster DM, Lee ST, Pandit-Taskar N, Fan AC, Allman P, Schmidt K, Tauchmanova L, Wheatcroft M, Behrenbruch C, Hayward CRW, Mulders P. [89Zr]Zr-girentuximab for PET-CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 Oct;25(10):1277-1287. doi: 10.1016/S1470-2045(24)00402-9. Epub 2024 Sep 10. PubMed 39270701 ↗
Powles T, Albiges L, Bex A, Comperat E, Grunwald V, Kanesvaran R, Kitamura H, McKay R, Porta C, Procopio G, Schmidinger M, Suarez C, Teoh J, de Velasco G, Young M, Gillessen S; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Aug;35(8):692-706. doi: 10.1016/j.annonc.2024.05.537. Epub 2024 May 22. No abstract available. PubMed 38788900 ↗

Individual participant data

Plan to share: No — Individual participant data are not planned to be shared.

Updates

1 registry update since Sep 25, 2026

Registered

First appeared on the registry. No changes since

Oct 8, 2026

Show all 1 update

Oct 8, 2026
First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT07865832
Lead sponsor: Liangyou Gu
Responsible party: Liangyou Gu (Principal Investigator, Chinese PLA General Hospital) — Sponsor-investigator
First posted: Oct 8, 2026
Start date: Nov 2026 (estimated)
Primary completion: Sep 2028 (estimated)
Completion: Sep 2029 (estimated)
Last update: Oct 8, 2026

Study contacts

Liangyou Gu

Contact

guliangyouyd1@126.com

+86 010 6693 7166

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Carcinoma, Renal Cell→

Start the discussion