PD-L1 t-haNK, NAI IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC

NCT06239220 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-583
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to test the safety and efficacy of the combination of PD-L1 t-haNK (modified immune cells), NAI (a manufactured protein that stimulates the immune system), and cetuximab (a targeted antibody) in treating advanced head and neck cancer. The names of the therapies involved in this study are:

• PD-L1 t-haNK cell therapy (a NK cell therapy infusion)
• NAI (a type of recombinant human superagonist)
• Cetuximab (a type of antibody)

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Cancer; Recurrent Head and Neck Cancer; Metastatic Head-and-neck Squamous-cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma

Keywords

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Cancer; Recurrent Head and Neck Cancer; Metastatic Head-and-neck Squamous-cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.

  Disease will be evaluated through imaging every 2 cycles on day 1 and 15 (each cycle is 28 days) and through study completion (an average of 1 year). ORR expected to be observed up to 1 year.

Secondary Outcomes (4)

• Grade 3-5 Treatment-related Toxicity Rate

  AE evaluated on treatment at day 1 and 15 on each cycle and up to 30 days after coming off study treatments. Median treatment duration for this study cohort was 18 months (range T1- T2).

• Median Duration of Response (DOR)

  Disease will be evaluated through imaging every 2 cycles on day 1 and 15 (each cycle is 28 days) and through study completion (an average of 1 year). In long-term follow-up, disease reported every 3-4 months, up to 3 years.

• Median Progression-Free Survival (PFS)

  Disease will be evaluated through imaging every 2 cycles on day 1 and 15 (a cycle is 28 days) and through study completion (an average of 1 year. In long-term follow-up, disease reported every 3-4 months, up to 3 years.

• Median Overall Survival (OS)

  Up to 3 years

Study Arms (2)

Dose Level 0: PD-L1 t-haNK + NAI + Cetuximab

EXPERIMENTAL

Dose level modifications of PD-L1 t-haNK and NAI due to toxicities will follow protocol specifications, starting at Dose Level 0 and de-escalating to Dose Level -1. Participants will complete: * Baseline visit. * Imaging scans every 8 weeks while on study. * Cycle 1 through End of Treatment: --Days 1 and 15 of 28 day cycle in the following order: Predetermined dose of PD-L1 t-haNK 1x daily, predetermined dose of NAI 1x daily, and predetermined dose of Cetuximab 1x daily. * End of Treatment visit with assessments. * Follow up: follow up every 3-4 months for up to 3 years after end of treatment. Longer-term follow-up every 6-12 months for up to 15 years.

Biological: PD-L1 t-haNK; Drug: Cetuximab; Biological: NAI

Dose Level -1: PD-L1 t-haNK + NAI + Cetuximab

EXPERIMENTAL

Dose level modifications of PD-L1 t-haNK and NAI due to toxicities will follow protocol specifications. Participants will complete: * Baseline visit. * Imaging scans every 8 weeks while on study. * Cycle 1 through End of Treatment: --Days 1 and 15 of 28 day cycle in the following order: Predetermined dose of PD-L1 t-haNK 1x daily, predetermined dose of NAI 1x daily, and predetermined dose of Cetuximab 1x daily. * End of Treatment visit with assessments. * Follow up: follow up every 3-4 months for up to 3 years after end of treatment. Longer-term follow-up every 6-12 months for up to 15 years.

Biological: PD-L1 t-haNK; Drug: Cetuximab; Biological: NAI

Interventions

NAI BIOLOGICAL

Recombinant human superagonist, via subcutaneous injection (under the skin) per protocol.

Also known as: Interleukin-15, IL-15, Anktiva

Dose Level -1: PD-L1 t-haNK + NAI + Cetuximab; Dose Level 0: PD-L1 t-haNK + NAI + Cetuximab

PD-L1 t-haNK BIOLOGICAL

Allogeneic, stable, clonal natural killer cell line product, via intravenous infusion (into the vein) per protocol.

Also known as: NK-92

Dose Level -1: PD-L1 t-haNK + NAI + Cetuximab; Dose Level 0: PD-L1 t-haNK + NAI + Cetuximab

Cetuximab DRUG

Epidermal growth factor receptor, via intravenous (into the vein) infusion per institutional standard of care.

Also known as: Erbitux

Dose Level -1: PD-L1 t-haNK + NAI + Cetuximab; Dose Level 0: PD-L1 t-haNK + NAI + Cetuximab

Eligibility Criteria

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

You may qualify if:

• Participants must have an existing histologically confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC) with evidence of recurrent, metastatic (R/M) or locoregionally advanced, incurable or unresectable disease from any mucosal subsite including oral cavity, oropharynx, larynx, hypopharynx, nasal cavity, and the paranasal sinuses.
• Participants must have at least one RECIST v1.1 measurable lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) ≥ 1 cm with CT scans or MR imaging.
• Must have had at least 1, but no more than 2, prior lines of prior systemic therapy for R/M HNSCC; one of these lines should have included anti-PD-1/L1 therapy.
• a.Platinum-based therapy as part of definitive/adjuvant or curative-intent treatment can count as 1 prior line of therapy if the subject progressed within 6 months of receiving therapy.
• b. At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (2 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE v5 grade ≤1 (or tolerable grade 2) or back to baseline (except for alopecia or peripheral neuropathy).
• Be ≥18 years of age on the day of signing informed consent.
• Must provide prior documentation on tumor PD-L1 expression status and HPV status (for oropharyngeal cancer cases), if available from the medical record.
• Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).
• Participants must have adequate organ and marrow function as defined below (within 14 days prior to study registration):
• a. ANC ≥1,000/mcL
• b. Hemoglobin ≥9 g/dL
• c. Platelets ≥100,000/mcL
• d. Total bilirubin ≤ upper limit of normal (ULN)
• e. AST(SGOT)/ALT(SGPT) ≤2.5x institutional ULN (or ≤1.5x institutional ULN if concomitant with alkaline phosphatase \>2.5x institutional ULN) or ≤5x ULN for those with liver metastases
• g. Serum creatinine ≤1.5x ULN or creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above 1.5x ULN

You may not qualify if:

• Have been previously treated with 3 or more lines of systemic therapy for R/M HNSCC.
• Have received radiation therapy (RT) within 10 days of starting protocol therapy.
• Solid organ transplant (allograft) recipients.
• Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging and off systemic steroids for at least 3 weeks prior to study registration) and have no evidence of new or enlarging brain metastases.
• A history of significant autoimmune disease as judged by the treating investigator and on active therapy including prednisone ≥10 mg daily dose equivalent of corticosteroids.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection; evidence of symptomatic congestive heart failure, unstable angina pectoris, stroke, or ventricular arrhythmia within 6 months of enrollment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions might include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Any known positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative). Patients with HIV are eligible if their plasma HIV viral load is undetectable at baseline on antiretroviral therapy.
• Subjects who are pregnant, or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Breastfeeding should be discontinued if the mother is treated on this protocol. Women who could potentially become pregnant while undergoing treatment on this protocol must be willing to use 2 methods of contraception.

Sponsors & Collaborators

• Glenn J. Hanna: lead
• ImmunityBio, Inc.: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Interleukin-15

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Glenn J Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn J Hanna, MD

CONTACT

617-632-3779; glenn_hanna@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: February 16, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)