Actively Recruiting

Phase 1
Age: 18Years +
All Genders
NCT07101432

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)

Led by M.D. Anderson Cancer Center · Updated on 2026-05-06

33

Participants Needed

1

Research Sites

216 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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

Official Title

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)

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients with histologically confirmed head and neck cancer, HPV positive or negative, that is locally advanced and unresectable or metastatic with 5 or fewer disease sites
  • Cancer that has relapsed or progressed after standard treatments or for which no standard treatment is available or effective
  • Tumors must show TROP2 expression level 2+ or 3+ by immunohistochemistry
  • At least 2 weeks since last cytotoxic chemotherapy and 3 days since last targeted therapy before lymphodepleting chemotherapy
  • Radiation therapy allowed to one or more disease sites before lymphodepleting chemotherapy
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Female patients not of childbearing potential or females of childbearing potential who agree to use contraception during treatment and 6 months after infusion
  • Negative pregnancy test for women of childbearing potential before chemotherapy
  • Agreement to use effective contraception for both female and male patients during study and 6 months after treatment
  • Measurable disease according to RECIST v1.1
  • Adequate organ function as defined by laboratory values within 10 days before lymphodepleting chemotherapy
  • Left ventricular ejection fraction greater than 50%
  • Adequate respiratory reserve with mild or no shortness of breath
  • Prior treatment with TROP2-targeted therapy allowed
  • Willingness to undergo mandatory blood collections and biopsies
  • Willingness to sign consent for long-term follow-up
  • Willingness to stay within a 2-hour drive of study site during first 4 weeks after infusion
  • Patients with prior or concurrent malignancy that does not interfere with study participation
  • Patients with known or treated cardiac disease with New York Heart Association Functional Classification Class 2B or better
  • Ability to understand and sign informed consent
Not Eligible

You will not qualify if you...

  • Pregnant, breastfeeding, or planning pregnancy during the study and 6 months after infusion
  • Received systemic anticancer therapy within 2 weeks or 5 half-lives (whichever is shorter) before lymphodepleting chemotherapy
  • Patients not recovered from adverse events of prior therapies to grade 1 or baseline, except some mild neuropathy or alopecia
  • Radiation therapy within 2 weeks before lymphodepleting chemotherapy if requiring corticosteroids or history of radiation pneumonitis
  • Received live vaccine within 6 weeks before infusion and for 24 months after
  • Prior CAR T or NK cell or other genetically modified T or NK cell therapy
  • Diagnosis of immunodeficiency or on chronic systemic steroids over 10 mg prednisone equivalent daily
  • History of second malignancy unless treated and disease-free for 2 years, except certain skin or in situ cancers
  • Active central nervous system metastases or carcinomatous meningitis
  • Active autoimmune disease requiring systemic treatment in past 2 years
  • History of interstitial lung disease requiring steroids or current pneumonitis/ILD
  • Active infection requiring systemic therapy
  • Known HIV infection
  • Known active or chronic hepatitis B or C infection
  • History of active tuberculosis
  • Any condition or therapy interfering with study participation or safety
  • Psychiatric or social issues limiting compliance
  • History of allogenic tissue or solid organ transplant
  • Significant cardiovascular disease within 12 months before chemotherapy, except controlled arrhythmia
  • Prolonged QT interval over 480 milliseconds
  • Bleeding or clotting disorders or risk of severe bleeding (patients on anticoagulation for DVT/PE allowed)
  • History of severe stomatitis or mucositis with prior therapy
  • Allergic reactions to cyclophosphamide, fludarabine, or similar agents used in the study

AI-Screening

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Trial Site Locations

Total: 1 location

1

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

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Research Team

G

Gohar Manzar, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

2

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