Phase I Study of Preconditioning Radiation Therapy With IL-15 Transduced TGFBR2 KO CAR.TROP2-engineered Cord Blood-derived NK Cells in Patients With Advanced Head and Neck Cancer (RADIANCE-NK)

NCT07101432 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-0561NCI-2025-05464
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended dose of an investigational therapy called chimeric antigen receptor (CAR).TROP2/interleukin (IL)15-transduced TGFBR2 KO cord blood (CB)-derived natural killer (NK) cells (TROP2 CAR/IL-15 TGFBR2 KO NK cells) that can be given with and without preconditioning radiation therapy in patients with advanced head and neck squamous cell carcinoma.

Conditions

Head and Neck Cancer

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 CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Phase 1 ESC Safety Lead-in - TROP2 CAR/IL-15 TGFBR2 KO NK Cells

EXPERIMENTAL

Participants will receive treatment on an outpatient basis

Drug: Fludarabine; Drug: Cyclophosphamide

Phase 1 ESC/EXP - TROP2 CAR/IL-15 TGFBR2 KO NK Cells + RT

EXPERIMENTAL

Participants will receive treatment on an outpatient basis

Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Fludarabine DRUG

Given by infusion

Phase 1 ESC Safety Lead-in - TROP2 CAR/IL-15 TGFBR2 KO NK Cells; Phase 1 ESC/EXP - TROP2 CAR/IL-15 TGFBR2 KO NK Cells + RT

Cyclophosphamide DRUG

Given by infusion

Phase 1 ESC Safety Lead-in - TROP2 CAR/IL-15 TGFBR2 KO NK Cells; Phase 1 ESC/EXP - TROP2 CAR/IL-15 TGFBR2 KO NK Cells + RT

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed head and neck cancer, either HPV+ or HPV-, that is locally advanced AND unresectable OR metastatic (≤5 sites of disease), which has relapsed or progressed following local standard treatments that are known to prolong survival, or for which no standard treatment is available or are no longer effective, or refused such therapy.
• Patient tumors must demonstrate TROP2 expression of 2+ or 3+ as determined by IHC at the MDACC CAP and CLIA accredited Clinical Laboratories.
• weeks from the last cytotoxic chemotherapy at the time of lymphodepleting chemotherapy; ≥3 days from last TKI or other targeted therapies at the time of lymphodepleting chemotherapy; ≥3 months from any cell therapy for any malignancy at the time of lymphodepleting chemotherapy; prior radiation therapy is allowed at the time of consent.
• RT allowed to ≥1 disease sites prior to the lymphodepleting chemotherapy. If there are additional measurable non-irradiated disease sites, this may be evaluated for response as well. If multiple lesions are irradiated, we advise that a single lesion will be treated to a higher dose and other lesions considered for lower doses, and that one site always remain unirradiated if a patient has ≥2 sites of disease.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of TROP2 CAR/IL-15 TGFBR2 KO NK cells in combination with radiation therapy in patients \<18 years of age, children are excluded from this study.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥3 months per PI or treating physician's discretion.
• A female patient is eligible to participate if at least one of the following conditions applies:
• a. Not a woman of childbearing potential (WOCBP). OR
• A WOCBP who agrees to follow the contraceptive guidelines in Appendix 5 during the study treatment period and for 6 months post-TROP2 CAR/IL-15 TGFBR2 KO NK cell infusion.
• WOCBP must have a negative urine pregnancy test within 72 hours prior to the start of lymphodepleting chemotherapy. If a WOCBP has a urine pregnancy test that cannot be confirmed as negative, a serum (beta-human chorionic gonadotropin \[B-hCG\]) pregnancy test will be required.
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• History of bilateral tubal ligation or another surgical sterilization procedure.

You may not qualify if:

• Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 6 months post TROP2 CAR/IL-15 TGFBR2 KO NK cell infusion.
• Has received systemic anticancer therapy within 2 weeks or 5 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy. For patients treated with monoclonal antibodies, at least 3 weeks must have elapsed prior to the start of lymphodepleting chemotherapy. Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks after the last dose of the previous investigational agent.
• Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI)/co-PIs. If a patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the start of lymphodepleting chemotherapy.
• If patients receive RT within 2 weeks of the start of lymphodepleting chemotherapy, they must not require corticosteroids, and not have had radiation pneumonitis.
• Has received a live vaccine within 6 weeks prior to TROP2 CAR/IL-15 TGFBR2 KO NK infusion and for at least 24 months post infusion. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Prior CAR T or NK cell or other genetically modified T or NK cell therapy.
• Has diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent).
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to patients who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
• Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate if they completed radiation therapy, are clinically stable, and without requirement of steroid treatment for at least 2 weeks prior to study enrollment.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
• History of interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD. 12. Active infection requiring systemic therapy.
• \. Known human immunodeficiency virus (HIV) infection.
• \. Known active or chronic hepatitis B or hepatitis C virus infection.
• \. Known history of active tuberculosis (Mycobacterium tuberculosis).
• \. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Gohar Manzar, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gohar Manzar, MD

CONTACT

713-792-4503; gsmanzar@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 3, 2025
• Study Start: November 4, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

US (1)