RECRUITING

PD-L1 T-haNK, N-803 IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this research study is to test the safety and efficacy of the combination of PD-L1 t-haNK (modified immune cells), N-803 (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) * N-803 (a type of recombinant human superagonist) * Cetuximab (a type of antibody)

Official Title

A Phase 2 Trial of PD-L1 T-haNK, N-803 IL-15 Superagonist (Anktiva), and Cetuximab for Immunotherapy-treated Patients with Recurrent, Metastatic HNSCC (QUILT-505)

Quick Facts

Study Start:2024-02-16

Study Completion:2027-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06239220

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * f. Serum creatinine ≤1.5x ULN or creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above 1.5x ULN * Baseline tumor measurements must be documented from imaging within 28 days prior to study registration. * Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 7 days of study registration. Male subjects should use a condom as a contraceptive during the study and through 6 months after the last dose of study drugs. * 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.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* 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
* f. Serum creatinine ≤1.5x ULN or creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above 1.5x ULN
* Baseline tumor measurements must be documented from imaging within 28 days prior to study registration.
* Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 7 days of study registration. Male subjects should use a condom as a contraceptive during the study and through 6 months after the last dose of study drugs.
* 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.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Glenn J Hanna, MD

CONTACT

617-632-3779

glenn_hanna@dfci.harvard.edu

Principal Investigator

Glenn J Hanna, MD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

Brigham and Women's Hospital

Boston, Massachusetts, 02115

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

United States

Collaborators and Investigators

Sponsor: Glenn J. Hanna

Glenn J Hanna, MD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-02-16

Study Completion Date2027-01-31

Study Record Updates

Study Start Date2024-02-16

Study Completion Date2027-01-31

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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