TROP2 CAR/IL-15 NK Cells for Head and Neck Cancer

Overseen By Gohar Manzar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Live vaccines, Corticosteroids

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of a new treatment using special immune cells called TROP2 CAR/IL-15 TGFBR2 KO NK cells, designed to target and kill cancer cells. It targets individuals with advanced head and neck cancer unresponsive to standard treatments. The study will evaluate these cells with and without pre-treatment radiation. Those whose head and neck cancer has recurred or spread after standard treatments may be suitable candidates. The trial includes multiple groups to assess the treatment's effectiveness under different conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial requires a break from certain medications before starting the study. You need to stop cytotoxic chemotherapy 2 weeks before, targeted therapies 3 days before, and any cell therapy 3 months before the lymphodepleting chemotherapy. It's best to discuss your specific medications with the trial team to ensure compliance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the safety and effectiveness of a new treatment for advanced head and neck cancer using specially modified cells. These cells are designed to better target cancer cells. Previous studies with similar cells have shown they can be safe for patients.

Although specific safety data for this treatment is limited, other treatments using similar cells have shown promising results with manageable side effects. Common side effects might include mild flu-like symptoms, such as fever or chills, due to the body's immune response. As this is an early-stage trial, the main goal is to find the safest dose, so researchers are closely monitoring the treatment for any serious side effects.

Overall, early research suggests this therapy could offer a new way to fight cancer with a focus on safety. However, because this is an early trial, the full safety profile is still being determined. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Researchers are excited about TROP2 CAR/IL-15 NK Cells because they offer a unique approach to tackling head and neck cancer. Unlike traditional treatments like surgery, radiation, or chemotherapy, this experimental therapy uses genetically engineered natural killer (NK) cells. These cells are modified to better recognize and attack cancer cells by targeting the TROP2 protein, which is often overexpressed in these cancers. Additionally, this treatment is enhanced with IL-15, a cytokine that boosts the activity and persistence of NK cells, potentially leading to more effective and sustained cancer cell elimination. This innovative approach could provide a powerful new option for patients who need alternatives to existing therapies.

What evidence suggests that TROP2 CAR/IL-15 NK Cells might be an effective treatment for head and neck cancer?

This trial will evaluate a new type of immune cell treatment for head and neck cancer. Participants will receive TROP2 CAR/IL-15 TGFBR2 KO NK Cells, designed to target a protein called TROP2, often found on cancer cells. Studies have shown that these modified cells can effectively kill cancer cells and may enhance the immune system's response with IL-15, a protein that supports immune cell growth. Early findings suggest that this approach could improve the ability to fight tumors in hard-to-treat cancers. Although more research is needed, the initial results are promising for those with head and neck cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Gohar Manzar, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced head and neck cancer, either HPV+ or HPV-, that's unresectable/metastatic and resistant to standard treatments. Must have good organ function, ECOG status of 0/1, measurable disease by RECIST v1.1, TROP2 expression in tumors, and be willing to follow study procedures. Excludes those with certain heart/lung diseases, active infections including HIV/hepatitis B/C/TB, recent other cancer therapies or live vaccines, history of severe allergies to trial drugs or similar compounds.

Inclusion Criteria

My organs are functioning well enough for chemotherapy.

My head and neck cancer is advanced, can't be surgically removed, or has spread, and standard treatments haven't worked or were refused.

Life expectancy ≥3 months per PI or treating physician's discretion.

Exclusion Criteria

I have had lung disease that needed steroids or currently have lung inflammation.

I am HIV positive.

I haven't had serious heart problems in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconditioning Radiation Therapy

Participants receive preconditioning radiation therapy before CAR-NK cell infusion

2 weeks

1 visit (in-person)

Treatment

Participants receive TROP2 CAR/IL-15 TGFBR2 KO NK cells with or without preconditioning radiation therapy

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety, tolerability, and tumor response after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• TROP2/IL-15 TGFBR2 KO NK Cells

Trial Overview The trial is testing the safety and optimal dose of a new therapy using genetically modified NK cells targeting TROP2 (TROP2 CAR/IL-15 TGFBR2 KO NK cells) for head and neck cancers. It will evaluate the effects with/without preconditioning radiation therapy.

How Is the Trial Designed?

Group I: Phase 1 ESC/EXP - TROP2 CAR/IL-15 TGFBR2 KO NK Cells + RT Experimental Treatment 2 Interventions

Participants will receive treatment on an outpatient basis

Group II: Phase 1 ESC Safety Lead-in - TROP2 CAR/IL-15 TGFBR2 KO NK Cells Experimental Treatment 2 Interventions

Participants will receive treatment on an outpatient basis

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07101432

Phase I Study of Preconditioning Radiation Therapy With IL ... To quantify the progression-free survival, overall survival, and the duration of responses of TGFBR2 KO CAR.TROP2/IL15-transduced CB-derived NK ...

2. withpower.com withpower.com/trial/phase-1-head-and-neck-neoplasms-1-2026-2b6a0

TROP2 CAR/IL-15 NK Cells for Head and Neck Cancer ... TROP2/IL-15 TGFBR2 KO NK Cells will have tolerable side effects & efficacy for patients with Head and Neck Cancers and Head and Neck Cancers. Learn more about

3. sciencedirect.com sciencedirect.com/science/article/pii/S1535610825003277

Genome-wide CRISPR screens identify critical targets to ... IL-15-armored CAR-NK cells targeting TROP2 or CD70 similarly displayed enhanced cytotoxicity against multiple solid cancer models following ...

4. reporter.nih.gov reporter.nih.gov/project-details/11067768

TROP2-Directed CAR-NK Cells for the Immunotherapy ... We hypothesize that targeting TROP2 with iC9/TROP2CAR/IL-15 NK cells will greatly improve outcomes in PDAC and that by deleting the metabolic immune checkpoint ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-02697

Genetically Engineered Cells (TGFBR2 KO CAR27/IL-15 ... The researchers think that IL-15 may improve the effectiveness of the modified T cells, and it may also strengthen the immune system to fight cancer. Giving ...

6. mdanderson.org mdanderson.org/content/dam/mdanderson/documents/about-md-anderson/about-us/legal-and-policy/IBC-Meeting-Minutes-20250909.pdf

Institutional Biosafety Meeting Minutes, Sept. 9, 2025 dose of TROP2 CAR/IL-15 TGFBR2 KO NK cells, given alone or with radiation therapy, in patients with advanced head and neck cancer. These ...

7. cell.com cell.com/cancer-cell/fulltext/S1535-6108(25)00327-7

Genome-wide CRISPR screens identify critical targets to ... IL-15-armored CAR-NK cells targeting TROP2 or CD70 similarly displayed enhanced cytotoxicity against multiple solid cancer models following ...