This example Phase 1/2 protocol evaluates allogeneic EGFR/HER2 dual-target CAR-NK cells in adults with recurrent or metastatic HNSCC whose tumors meet protocol-defined co-expression criteria for EGFR and HER2/ERBB2. The study is designed as a biomarker-enriched, open-label, non-randomized trial with a dose-escalation safety lead-in followed by an expansion cohort at the recommended Phase 2 dose (RP2D).
Age 18 to 75 years at the time of consent.
Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx that is recurrent or metastatic and not amenable to curative surgery or radiotherapy.
Tumor meets protocol-defined central biomarker criteria for both EGFR and HER2 / ERBB2. Suggested example thresholds: EGFR membranous IHC 2+ / 3+ in at least 50% of viable tumor cells and HER2 IHC 2+ / 3+ in at least 10% of viable tumor cells and / or protocol-defined genomic amplification / activating alteration.
Disease progression on or after at least one prior systemic regimen for recurrent / metastatic disease, including platinum therapy and PD-1 / PD-L1 inhibitor unless contraindicated or not appropriate. Prior cetuximab is allowed.
Nasopharyngeal carcinoma, salivary gland malignancy, cutaneous squamous cell carcinoma, non-squamous histology, or carcinoma of unknown primary.
Untreated, unstable, or symptomatic central nervous system metastases or leptomeningeal disease.
Prior gene-modified adoptive cell therapy (for example CAR-T, CAR-NK, or TCR-T) within a protocol-defined washout period, or prior allogeneic stem-cell transplant with active graft-versus-host disease.
Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection; active hepatitis B or C with detectable viral load; or uncontrolled HIV infection.
Single group
EGFR/HER2 Dual-Target CAR-NK Cells
Biological/VaccineAllogeneic donor-derived activated /expanded NK cells engineered to express a dual EGFR/HER2 chimeric antigen receptor, membrane-bound IL-15, and an inducible caspase-9 safety switch
Fludarabine
DrugLymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
Cyclophosphamide
DrugLymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
Incidence of dose-limiting toxicities (DLTs)
Determination of the recommended Phase 2 dose
Incidence of treatment-emergent adverse events
Objective response rate (ORR) by RECIST 1.1
Disease control rate (DCR)
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