Advanced or Metastatic Clear Cell Renal Cell CarcinomaPhase 1/2DUAL-NK RCCNCT07551349
Dual-target CD70/CAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma
A Phase 1/2 study testing EB-701/CA9-NK and Fludarabine in people with Advanced or Metastatic Clear Cell Renal Cell Carcinoma, run by Beijing Biotech at 1 site in China.
Trial summary
Phase 1/2 study evaluates the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CD70/CAIX CAR-NK cells after fludarabine/cyclophosphamide lymphodepletion in adults with advanced or metastatic clear cell RCC that has progressed after standard therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Clear Cell Renal Cell Carcinoma
- What is being tested?
- EB-701/CA9-NK and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 2 Feb 2026to 17 Apr 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and willingness to comply with protocol procedures.
- Age >= 18 years at the time of consent.
- Histologically confirmed unresectable or metastatic clear cell RCC, or RCC with a clear-cell component, with radiographic progression after standard therapy.
- Prior exposure to at least one PD-1 / PD-L1-based regimen and at least one VEGF-pathway targeted regimen, or documented intolerance / unsuitability for available standard systemic options.
- At least one measurable lesion by RECIST 1.1.
- Available archival tumor tissue or willingness to undergo fresh biopsy for central biomarker testing; protocoldefined tumor positivity for CD70 and/or CAIX is required. Dual-positive cases are preferred for the biomarkerexpansion portion.
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- ECOG performance status 0-1.
- Adequate marrow, liver, cardiac, pulmonary, and renal function as defined by the protocol (for example, ANC, platelets, bilirubin, AST/ALT, creatinine clearance, oxygen saturation, and left ventricular function within protocoldefined limits).
- Life expectancy of at least 12 weeks.
- Negative pregnancy test for participants of childbearing potential and agreement to highly effective contraception during protocol-defined risk windows.
- Previously treated brain metastases are allowed if clinically stable and off escalating corticosteroids for at least 14 days before lymphodepletion.
Who cannot join
- Active, untreated, or symptomatic central nervous system metastases, leptomeningeal disease, or uncontrolled seizure disorder.
- Prior gene-modified cellular therapy (including prior CAR-T, CAR-NK, CAR-NKT, or TCR-engineered therapy) within the protocol-defined washout window.
- Prior allogeneic stem cell transplant or solid organ transplant with ongoing clinically significant immunosuppression.
- Active autoimmune disease requiring systemic immunosuppressive treatment; physiologic replacement doses are permitted.
- Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, tuberculosis, or sepsis.
- Clinically significant hepatobiliary disease that could increase risk from CAIX-directed therapy, such as active cholangitis, primary sclerosing cholangitis, biliary obstruction, Child-Pugh B/C cirrhosis, or prior hepatic venoocclusive disease.
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- Clinically significant cardiovascular disease (for example, unstable angina, recent myocardial infarction, uncontrolled arrhythmia, or clinically meaningful heart failure).
- Systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days before lymphodepletion, unless required as physiologic replacement.
- Pregnancy or breastfeeding.
- Another active invasive malignancy requiring systemic treatment, except for protocol-defined low-risk exceptions.
- Known hypersensitivity to fludarabine, cyclophosphamide, or a critical study-product excipient.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Zhen J Peng, Phd, +86 13076790039, Zhen-Peng@beijing-biotech.com
About this study
Official title: An Open-Label, Multicenter, Phase 1/2 Study of Allogeneic Dual-target CD70/CAIX (CA9) Chimeric Antigen Receptor Natural Killer Cells in Adults With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
Phase 1/2 study evaluates the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CD70/CAIX CAR-NK cells after fludarabine/cyclophosphamide lymphodepletion in adults with advanced or metastatic clear cell RCC that has progressed after standard therapy. The study is designed to determine a recommended dose and schedule, characterize hepatobiliary safety, and explore whether CD70-high, CAIX-high, or dual-high tumors derive the greatest benefit. Biomarker-defined activity signals will be used to guide whether later development should prioritize CD70, CAIX/CA9, or continued dual-targeting.
Read the detailed description
Advanced clear cell RCC remains difficult to treat after immune checkpoint blockade and VEGF-pathway therapy. Both CD70 and CAIX are attractive RCC targets: CAIX is broadly expressed in clear cell RCC, while CD70 is frequently overexpressed and has already generated encouraging clinical cell-therapy signals in RCC [3-11]. The investigational product in this example is an allogeneic, cord blood-derived NK cell product engineered to express a dual CAR recognizing CD70 and CAIX/CA9, membrane-bound IL-15 to enhance persistence, and an inducible caspase-9 safety switch to improve controllability. The allogeneic CAR-NK strategy is intended to provide an off-the-shelf platform with lower theoretical risk of graft-versus-host disease than allogeneic T-cell products and with innate NK killing as a complementary antitumor mechanism [1, 2, 11]. The study uses a standard dose-escalation phase followed by a biomarker-guided expansion phase. All participants receive lymphodepletion with fludarabine and cyclophosphamide and then one infusion of dual-target CAR-NK cells on Day 0; an optional second infusion on Day 15 is allowed for participants without doselimiting toxicity, uncontrolled cytokine-mediated toxicity, or rapid progression.
During expansion, participants remain in a single treatment arm but are prospectively analyzed in CD70-high, CAIX-high, and dual-high subgroups. Because earlier CAIX CAR-T studies in metastatic RCC reported on-target hepatobiliary toxicity related to low-level CAIX expression in biliary epithelium, this example protocol incorporates enhanced liver screening, exclusion of significant biliary disease, staggered first-patient dosing at each dose level, frequent liver function monitoring, and an explicit early stopping rule for recurrent protocoldefined hepatobiliary toxicity [5, 6].
The translational objective is not only to identify a recommended phase 2 dose but also to learn which antigen context appears most actionable in patients. If activity clusters in CD70-high tumors with cleaner safety, later development may pivot toward a CD70-led construct. If CAIX-high tumors uniquely benefit without meaningful hepatobiliary toxicity, CAIX/CA9 may remain central. If dual-high tumors clearly outperform single-high tumors without added risk, the dual-target program should continue.
- Being tested
- EB-701/CA9-NK, Fludarabine
- Keywords
- RCC, kidney cancer, clear cell renal cell carcinoma
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma, Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EB-701/CA9-NKBiological
dual-target allogeneic CAR-NK cells (single infusion on Day 0; optional second infusion on Day 15 if safety criteria are met)
FludarabineDrug
lymphodepletion
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion | Experimental | Not described Receives: Biological: EB-701/CA9-NK; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Incidence of dose-limiting toxicities (DLTs) during the DLT window, graded by CTCAE v5.0
Measured: 28 Days
Determination of recommended phase 2 dose
Measured: 8 weeks
Secondary outcomes (2)
Objective response rate (ORR) per RECIST 1.1 by independent radiologic review
Measured: 6 months
Overall Survival (OS)
Overall Survival (OS) is the length of time from diagnosis or treatment start that patients remain alive
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2026
- Study start2 Feb 2026
- Primary completion14 Apr 2027 (estimated)
- Study completion17 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Beijing BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Up to 36 participants will be treated. Phase 1 uses a 3+3 dose-escalation design with three planned dose levels of dual-target CAR-NK cells following lymphodepletion. Dose level review is performed after Day 28 safety assessment for each cohort. After the recommended phase 2 dose / schedule (RP2D / RP2S) is declared, an expansion phase enrolls additional participants into biomarker-defined analytic subgroups (CD70-high, CAIX-high, dual-high) within the same single treatment arm. These subgroups are used for exploratory target-selection analysis rather than for randomization. Staggered enrollment is required for the first two participants at each dose level. Optional repeat infusion on Day 15 is permitted at investigator and sponsor discretion if predefined safety criteria are met.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07551349
- Sponsor's protocol ID
- EBNK-RCC-70CA9-120
- Acronym
- DUAL-NK RCC
- Status last verified
- Apr 2026
- First submitted
- 18 Apr 2026
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter, Phase 1/2 Study of Allogeneic Dual-target CD70/CAIX (CA9) Chimeric Antigen Receptor Natural Killer Cells in Adults With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07551349
- Acronym / sponsor ID
- DUAL-NK RCC / EBNK-RCC-70CA9-120
- Keywords
- RCC, kidney cancer, clear cell renal cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 14 Apr 2027 (estimated)
- Study completion
- 17 Apr 2028 (estimated)
- First posted
- 24 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1/2 study evaluates the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CD70/CAIX CAR-NK cells after fludarabine/cyclophosphamide lymphodepletion in adults with advanced or metastatic clear cell RCC that has progressed after standard therapy. The study is designed to determine a recommended dose and schedule, characterize hepatobiliary safety, and explore whether CD70-high, CAIX-high, or dual-high tumors derive the greatest benefit. Biomarker-defined activity signals will be used to guide whether later development should prioritize CD70, CAIX/CA9, or continued dual-targeting.
Detailed description
Advanced clear cell RCC remains difficult to treat after immune checkpoint blockade and VEGF-pathway therapy. Both CD70 and CAIX are attractive RCC targets: CAIX is broadly expressed in clear cell RCC, while CD70 is frequently overexpressed and has already generated encouraging clinical cell-therapy signals in RCC [3-11]. The investigational product in this example is an allogeneic, cord blood-derived NK cell product engineered to express a dual CAR recognizing CD70 and CAIX/CA9, membrane-bound IL-15 to enhance persistence, and an inducible caspase-9 safety switch to improve controllability. The allogeneic CAR-NK strategy is intended to provide an off-the-shelf platform with lower theoretical risk of graft-versus-host disease than allogeneic T-cell products and with innate NK killing as a complementary antitumor mechanism [1, 2, 11]. The study uses a standard dose-escalation phase followed by a biomarker-guided expansion phase. All participants receive lymphodepletion with fludarabine and cyclophosphamide and then one infusion of dual-target CAR-NK cells on Day 0; an optional second infusion on Day 15 is allowed for participants without doselimiting toxicity, uncontrolled cytokine-mediated toxicity, or rapid progression.
During expansion, participants remain in a single treatment arm but are prospectively analyzed in CD70-high, CAIX-high, and dual-high subgroups. Because earlier CAIX CAR-T studies in metastatic RCC reported on-target hepatobiliary toxicity related to low-level CAIX expression in biliary epithelium, this example protocol incorporates enhanced liver screening, exclusion of significant biliary disease, staggered first-patient dosing at each dose level, frequent liver function monitoring, and an explicit early stopping rule for recurrent protocoldefined hepatobiliary toxicity [5, 6].
The translational objective is not only to identify a recommended phase 2 dose but also to learn which antigen context appears most actionable in patients. If activity clusters in CD70-high tumors with cleaner safety, later development may pivot toward a CD70-led construct. If CAIX-high tumors uniquely benefit without meaningful hepatobiliary toxicity, CAIX/CA9 may remain central. If dual-high tumors clearly outperform single-high tumors without added risk, the dual-target program should continue.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Up to 36 participants will be treated. Phase 1 uses a 3+3 dose-escalation design with three planned dose levels of dual-target CAR-NK cells following lymphodepletion. Dose level review is performed after Day 28 safety assessment for each cohort. After the recommended phase 2 dose / schedule (RP2D / RP2S) is declared, an expansion phase enrolls additional participants into biomarker-defined analytic subgroups (CD70-high, CAIX-high, dual-high) within the same single treatment arm. These subgroups are used for exploratory target-selection analysis rather than for randomization. Staggered enrollment is required for the first two participants at each dose level. Optional repeat infusion on Day 15 is permitted at investigator and sponsor discretion if predefined safety criteria are met.
| Arm | Type | Receives |
|---|---|---|
| Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion | Experimental | Biological: EB-701/CA9-NK, Drug: Fludarabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent and willingness to comply with protocol procedures.
- Age >= 18 years at the time of consent.
- Histologically confirmed unresectable or metastatic clear cell RCC, or RCC with a clear-cell component, with radiographic progression after standard therapy.
- Prior exposure to at least one PD-1 / PD-L1-based regimen and at least one VEGF-pathway targeted regimen, or documented intolerance / unsuitability for available standard systemic options.
- At least one measurable lesion by RECIST 1.1.
Key exclusion criteria (11 listed)
- Active, untreated, or symptomatic central nervous system metastases, leptomeningeal disease, or uncontrolled seizure disorder.
- Prior gene-modified cellular therapy (including prior CAR-T, CAR-NK, CAR-NKT, or TCR-engineered therapy) within the protocol-defined washout window.
- Prior allogeneic stem cell transplant or solid organ transplant with ongoing clinically significant immunosuppression.
- Active autoimmune disease requiring systemic immunosuppressive treatment; physiologic replacement doses are permitted.
- Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV, tuberculosis, or sepsis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EB-701/CA9-NKdual-target allogeneic CAR-NK cells (single infusion on Day 0; optional second infusion on Day 15 if safety criteria are met) | Biological | Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion |
| Fludarabinelymphodepletion | Drug | Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Incidence of dose-limiting toxicities (DLTs) during the DLT window, graded by CTCAE v5.0
Determination of recommended phase 2 dose
Time frame: 8 weeks
2 secondary outcomes
Objective response rate (ORR) per RECIST 1.1 by independent radiologic review
Time frame: 6 months
Overall Survival (OS)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EB-701/CA9-NK and Fludarabine in people with Advanced or Metastatic Clear Cell Renal Cell Carcinoma, run by Beijing Biotech at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact shan S Lu, Phd (+86 13076790030, Seni-Lu@beijing-biotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026; AzTrials last refreshed its copy on 6 Nov 2026.