Dual-target CD70/CAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma

NCT07551349 | Recruiting Phase 1 DMC

• 1 other identifier: EBNK-RCC-70CA9-120
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced or Metastatic Clear Cell Renal Cell Carcinoma

Keywords

RCC; kidney cancer; clear cell renal cell carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  Incidence of dose-limiting toxicities (DLTs) during the DLT window, graded by CTCAE v5.0

  28 Days

• Determination of recommended phase 2 dose

  8 weeks

Secondary Outcomes (2)

• Objective response rate (ORR) per RECIST 1.1 by independent radiologic review

  6 months

• Overall Survival (OS)

  12 months

Study Arms (1)

Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion

EXPERIMENTAL

Biological: EB-701/CA9-NK; Drug: Fludarabine

Interventions

EB-701/CA9-NK BIOLOGICAL

dual-target allogeneic CAR-NK cells (single infusion on Day 0; optional second infusion on Day 15 if safety criteria are met)

Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion

Fludarabine DRUG

lymphodepletion

Experimental: Dual-target CD70/CAIX CAR-NK cells after lymphodepletion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

fludarabine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Central Study Contacts

shan S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The trial is open-label because the main objectives are dose finding, real-time toxicity review, cell-product release management, and intensive translational monitoring.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 18, 2026
• First Posted: April 24, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): April 17, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

CN (1)