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Squamous Cell Carcinoma of the Head and NeckPhase 1NCT04290546

CIML NK Cell in Head & Neck Cancer

A Phase 1 study testing Interleukin-15 Superagonist (N-803), CIML NK cell Infusion and Ipilimumab in people with Squamous Cell Carcinoma of the Head and Neck and Recurrent Head and Neck Squamous Cell Carcinoma, run by Dana-Farber Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This research study is evaluating the safety and efficacy of a combination drug and biologic therapy in patients with advanced head and neck cancer. This research study involves the following drugs and biologics: CIML NK donor cells IL-15 superagonist Ipilimumab Cetuximab Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Interleukin-15 Superagonist (N-803), CIML NK cell Infusion and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
20 Jul 2020to 16 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed, recurrent or metastatic squamous cell carcinoma of the head neck (including oral cavity, oropharynx, larynx, hypopharynx, paranasal sinuses) or salivary gland carcinoma (including adenoid cystic carcinoma and non-adenoid cystic carcinoma histologies)
  • Any HPV status or smoking history is permitted. Oropharyngeal cancer patients are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV PCR or ISH testing
  • Available haploidentical donor that is willing and eligible for non-mobilized collection
  • Prior exposure to a platinum-containing regimen (either in the definitive or advanced, recurrent/metastatic setting) and exposure to a PD-1/L1 inhibitor is required for SCCHN patients only
  • Age 18 years or older
  • ECOG performance status ≤ 2 (see Appendix A).
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  • No systemic corticosteroid therapy (≤ 10 mg of prednisone or equivalent dose of systemic steroids for non-autoimmune indications for at least 4 weeks prior to NK cell infusion).
  • Ability to understand and the willingness to sign a written informed consent document.
  • Negative pregnancy test for women of childbearing potential only. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
  • The effects of CIML NK cells and N-803 on the developing human fetus are unknown.
  • For this reason, WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for up to 26 weeks after the last dose of all investigational products (up to 16 weeks after the last N-803 dose), in such a manner that the risk of pregnancy is minimized. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Willing to provide blood and tissue from diagnostic biopsy and at the time of surgery
  • Participants must have normal organ and marrow function as defined below:
  • leukocytes ≥ 2,500/mcL
  • absolute neutrophil count ≥ 1,000/mcL
  • platelets ≥ 90,000/mcL
  • total bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤ 3x institutional upper limit of normal
  • creatinine within normal institutional limits OR
  • creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Oxygen saturation: ≥ 90% on room air
  • Left ventricular ejection fraction (cardiac function) > 40%

Who cannot join

  • Patients with nasopharyngeal carcinoma are not eligible
  • Participants who have had anti-tumor chemotherapy or other investigational agents within 2 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 3 weeks prior, or those who have not recovered from adverse events due to agents administered more than 3 weeks prior.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to N-803 or other agents used in study.
  • Solid organ transplant (allograft) recipients.
  • Participants who are receiving any other investigational agents.
  • Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
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  • Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [Wegener's granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g. Guillain- Barre syndrome and myasthenia gravis). Patients with Hashimoto thyroiditis are eligible.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and N-803 and with the potential for teratogenic or abortifacient effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and N-803, breastfeeding should be discontinued if the mother is treated on this study.
  • HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high-risk of lethal treatment-related hepatotoxicity in the setting of marrow suppression.
  • Known non-infectious pneumonitis or any history of interstitial lung disease.
  • Receipt of a live vaccine within 30 days of start of study treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 1 Trial of CTLA-4 Inhibition, With or Without Cetuximab, and in Combination With Memory-like Natural Killer (NK) Cell Immune Cell Therapy in Advanced Head & Neck Cancer

This research study is evaluating the safety and efficacy of a combination drug and biologic therapy in patients with advanced head and neck cancer.

This research study involves the following drugs and biologics:

  • CIML NK donor cells
  • IL-15 superagonist
  • Ipilimumab
  • Cetuximab
Read the detailed description

This is a three-part, non randomized, open label, single site Phase 1 study. The purpose of this research study is to obtain information on the safety and effectiveness of this combination of study drugs to treat advanced head and neck. The experimental combination therapy in this study involves CIML NK cells from a haploidentical donor (meaning cells from another person with similar immune proteins), IL-15, participants in cohort 2 will also receive ipilimumab, and participants in cohort 3 will receive cetuximab. CIML NK cells are an allogeneic cell product derived from qualified donor natural killer (NK) cells that have been bathed in special proteins to help to identify and treat certain advanced cancers.

  • Participants who fulfill eligibility criteria will be entered into the trial CTLA-4 Inhibition in Combination with Memory-like Natural Killer (NK) Cell Immune Cell Therapy in Advanced Head \& Neck Cancer.

The study consists of 3 parts:

  • Cohort 1 CIML NK cells without ipilimumab
  • The investigators are looking the highest dose of the study intervention that can be administered safely without severe or unmanageable side effects in participants that have advanced head and neck cancer, not everyone who participates in this research study will receive the same dose of the study intervention. The dose given will depend on the number of participants who have been enrolled prior and how well the dose was tolerated
  • Cohort 2 participants will be treated at the respective dose (at or below the Maximum Tolerated Dose), as determined during Cohort plus a lead-in dose of ipilimumab
  • Cohort 3 participants will be treated at the respective dose (at or below the Maximum Tolerated Dose), as determined during Cohort plus infusions of cetuximab
  • It is expected that about 25 people will take part in this research study.

This research study is a Phase I clinical trial, which tests the safety of investigational drugs and tries to define the appropriate dose of the investigational drugs to use for further studies.

"Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved CIML NK cells as treatment for any disease.

The U.S. Food and Drug Administration (FDA) has not approved IL-15 as a treatment for any disease.

The U.S. Food and Drug Administration (FDA) has not approved ipilimumab for your specific disease but it has been approved for other uses.

The U.S. Food and Drug Administration (FDA) has approved cetuximab for your specific disease.

Being tested
Interleukin-15 Superagonist (N-803), CIML NK cell Infusion, Ipilimumab, Cetuximab
Keywords
Squamous Cell Carcinoma of the Head and Neck, Recurrent Head and Neck Squamous Cell Carcinoma
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interleukin-15 Superagonist (N-803)Drug

    -- Starting the day after (Cycle 1, Day +1) CIML NK-enriched cell infusion, at least 12 hours after CIML NK cell infusion is completed and up to 48 hours after CIML NK cell infusion, each participant will receive N-803 dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).

    N-803 dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles) for cohorts 1 and 2, and 6 total doses in cohort 3. The dose should be calculated based on body weight at study entry, and recalculated only if greater than 10% change in weight.

  • CIML NK cell InfusionBiological

    Also called cytokine induced memory-like natural killer

    (Dose 0 or -1) infused on Day 0

  • IpilimumabDrug

    Also called CTLA-4 inhibitor

    single dose of lead-in ipilimumab via iv per protocol determined dose

  • CetuximabDrug

    Also called EGFR inhibitor

    Starting day +15, every 14 days for 8 total doses via IV per protocol

Study groups in NCT04290546
Study groupRoleWhat they receive
Cohort I without Ipilimumab Lead inExperimentalHaploidentical donor derived CIML NK cell infusion with subcutaneous N-803 for eligible patients with platinum-refractory and immune checkpoint blockade-refractory, advanced head and neck squamous cell carcinoma (Cohort 1) * CIML NK cell infusion (Dose 0 or -1) infused on Day 0. * Interleukin-15 Superagonist dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).
Receives: Drug: Interleukin-15 Superagonist (N-803); Biological: CIML NK cell Infusion
Cohort 2 with Ipilimumab Lead InExperimentalCohort 2 treated with an ipilimumab lead-in prior to CIML NK cell infusion after safety is established with the NK cell and N-803 treatments alone. * Participants in the ipilimumab subgroup (Cohort 2) will receive a single dose of lead-in ipilimumab via iv per protocol determined dose followed by lymphodepleting chemotherapy on Day -6 for a total of 5-days, prior to receiving CIML NK cell infusion. * CIML NK cell infusion-Highest Dosed per cohort 1, infused on day 0 * Interleukin-15 Superagonist (N-803) Administration -- dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles). * Cohort 2 will receive the highest number of CIML NK cells that is still considered safe and ipilimumab.
Receives: Drug: Interleukin-15 Superagonist (N-803); Biological: CIML NK cell Infusion; Drug: Ipilimumab
Cohort 3 with Cetuximab InfusionsExperimentalCohort 3 treated with CIML NK cell infusion after safety is established with the NK cell and N-803 treatments alone, followed by cetuximab infusions. * - Participants in cetuximab subgroup (Cohort 3) will receive lymphodepleting chemotherapy on Day -6 for a total of 5-days, prior to receiving CIML NK cell infusion. * CIML NK cell infusion-Highest Dosed per cohort 1, infused on day 0 * Interleukin-15 Superagonist (N-803) Administration -- dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles). * Cetuximab Administration --dosed at 500mg/m2 IV over 120 minutes for the first dose, then over 60 minutes for subsequent doses. This will be infused every 14 days for 8 doses started on day +15. * Cohort 3 will receive the highest number of CIML NK cells that is still considered safe and ipilimumab.
Receives: Drug: Interleukin-15 Superagonist (N-803); Biological: CIML NK cell Infusion; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Dose Limiting Toxicity

    All patients receiving any dose of study treatment will be evaluated for safety. DLTs overall and by dose level will be reported as proportions with 90% exact binomial confidence intervals.

    Measured: first dose of study treatment up to 100 days

Secondary outcomes (4)

  1. objective response rate (ORR)

    reported as proportions with 90% exact binomial confidence intervals for all patients and by dose level

    Measured: 12 weeks

  2. complete response (CR) rate

    reported as proportions with 90% exact binomial confidence intervals for all patients and by dose level

    Measured: 12 weeks

  3. disease-free survival (DFS)

    Kaplan and Meier

    Measured: 1 year

  4. overall survival (OS) at 1-year following infusion

    Kaplan and Meier

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2020
  2. Study start20 Jul 2020
  3. Primary completion1 Sep 2024
  4. Study completion16 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04290546
Sponsor's protocol ID
19-505
Status last verified
Jun 2026
First submitted
27 Feb 2020
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • Shapiro RM, Sheffer M, Booker MA, Tolstorukov MY, Birch GC, Sade-Feldman M, Fang J, Li S, Lu W, Ansuinelli M, Dulery R, Tarannum M, Baginska J, Dwivedi N, Kothari A, Penter L, Abdulhamid YZ, Kaplan IE, Khanhlinh D, Uppaluri R, Redd RA, Nikiforow S, Koreth J, Ritz J, Wu CJ, Soiffer RJ, Hanna GJ, Romee R. First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer. J Hematol Oncol. 2025 Feb 14;18(1):17. doi: 10.1186/s13045-025-01669-3.

    PubMed 39948608

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Interleukin-15 Superagonist (N-803), CIML NK cell Infusion and Ipilimumab in people with Squamous Cell Carcinoma of the Head and Neck and Recurrent Head and Neck Squamous Cell Carcinoma, run by Dana-Farber Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Dose Limiting Toxicity (time frame: first dose of study treatment up to 100 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04290546, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

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