Dual-target CD70/CAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma (DUAL-NK RCC)

April 18, 2026 updated by: Beijing Biotech

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion
Drug: Fludarabine
lymphodepletion
Biological: EB-701/CA9-NK
dual-target allogeneic CAR-NK cells (single infusion on Day 0; optional second infusion on Day 15 if safety criteria are met)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
28 Days
Determination of recommended phase 2 dose
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) per RECIST 1.1 by independent radiologic review
Time Frame: 6 months
6 months
Overall Survival (OS)
Time Frame: 12 months
Overall Survival (OS) is the length of time from diagnosis or treatment start that patients remain alive
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2026

Primary Completion (Estimated)

April 14, 2027

Study Completion (Estimated)

April 17, 2028

Study Registration Dates

First Submitted

April 18, 2026

First Submitted That Met QC Criteria

April 18, 2026

First Posted (Actual)

April 24, 2026

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 18, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EBNK-RCC-70CA9-120

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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