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)
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)
⁃ 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
⁃ 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. Female subjects should not become pregnant or nurse a baby during the study and through 120 days after the last dose of study drugs. Male subjects should use a condom as a contraceptive during the study and through 120 days after the last dose of study drugs.
• Sperm donation is discouraged for up to 6 months after the last dose of study drug.
• Be willing and able to provide written informed consent for the trial.