Phase I Study of Allogeneic Transforming Growth Factor-beta Receptor Type 2 Knockout CD70 CAR NK Cells in Treatment Refractory Clear Cell Renal Cell Carcinoma

NCT07072234 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-0508NCI-2025-04901
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Testing an investigational cancer therapy called TGFBR-2 KO CD70 CAR NK cell therapy.

Conditions

Clear Cell Carcinoma; Phase 1; Growth Factor

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTACAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Dose-optimization phase

EXPERIMENTAL

Drug: Lymphodepleting chemotherapy; Drug: Dexamethasone; Drug: Fludarabine; Drug: Cyclophosphamate; Drug: TGFBR-2 KO CD70 CAR NK

Dose-expansion phase

EXPERIMENTAL

Drug: Lymphodepleting chemotherapy; Drug: Dexamethasone; Drug: Fludarabine; Drug: Cyclophosphamate; Drug: TGFBR-2 KO CD70 CAR NK

Interventions

Lymphodepleting chemotherapy DRUG

Given by IV

Dose-expansion phase; Dose-optimization phase

Dexamethasone DRUG

Given PO

Dose-expansion phase; Dose-optimization phase

Fludarabine DRUG

Given by IV

Dose-expansion phase; Dose-optimization phase

Cyclophosphamate DRUG

Given by IV

Dose-expansion phase; Dose-optimization phase

TGFBR-2 KO CD70 CAR NK DRUG

Given by IV

Dose-expansion phase; Dose-optimization phase

Eligibility Criteria

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

You may not qualify if:

• Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated withthe previous anticancer treatment, as determined by the PI. Toxicities related to priorsurgery, radiation, prior systemic immune checkpoint inhibitors and chemotherapy should be resolved to Grade 1 or below prior to lymphodepletion.
• Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management or not responding to appropriate therapy. Note: Participants with simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Known active hepatitis B or C.
• Known human immunodeficiency virus (HIV).
• Presence of active neurological disorder(s).
• Active autoimmune disease within 12 months of enrollment (excluding low-grade psoriasis or well-controlled autoimmune thyroid disease).
• Amyloidosis or POEMS syndrome.
• Symptomatic or uncontrolled central nervous system involvement or signs of cord compression. In the case radiation therapy is indicated, the washout must be at least 14 days.
• Participants must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post resection or post radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-life-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the Participant's ability to participate and/or complete this trial. Examples include but are not limited to urothelial cancer Grade Ta or T1 and adenocarcinoma of the prostate treated by active surveillance.
• Presence of any other serious medical condition that may endanger the Participant at investigator's discretion, including but not limited to:
• New York Heart Association Class III or IV heart failure
• Myocardial infarction or stroke ≤ 26 weeks prior to CAR NK cell infusion
• Unstable angina within ≤ 13 weeks prior to CAR NK cell infusion unless the underlying disease has been corrected by procedural intervention (e.g., stent, bypass)
• Severe aortic stenosis
• Uncontrolled arrhythmia. PI approval is required for Participants with arrhythmia who may be included as an exception.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Adenocarcinoma, Clear Cell

Interventions

Dexamethasone; fludarabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Andrew C Johns, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew C Johns, MD

CONTACT

713-745-0138; acjohns@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 18, 2025
• Study Start: September 25, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (1)