EGFR/HER2 Dual-Target CAR-NK Cells for Recurrent or Metastatic HNSCC

Summary

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).

Eligibility

Inclusion Criteria:

* 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.
* At least one measurable lesion by RECIST 1.1.
* ECOG performance status 0 to 1.
* Adequate marrow, renal, hepatic, cardiac, and pulmonary function per protocol-defined laboratory thresholds.
* Life expectancy of at least 12 weeks.
* Availability of archival tissue or willingness to provide fresh tumor tissue for central biomarker testing; willingness to undergo serial blood sampling and optional research biopsy if medically feasible.
* Negative pregnancy test for participants of childbearing potential and agreement to use highly effective contraception during protocol-defined treatment and follow-up windows.
* Ability to understand and sign informed consent.

Exclusion Criteria:

* 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.
* Active autoimmune disease requiring systemic immunosuppression, or chronic corticosteroid use above the protocoldefined threshold before lymphodepletion.
* Clinically significant interstitial lung disease, oxygen dependence, or another serious pulmonary condition that would materially increase cell-therapy risk.
* Clinically significant cardiovascular disease including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, uncontrolled hypertension, or symptomatic heart failure.
* Major surgery within 28 days before lymphodepletion, or anticancer therapy / investigational therapy within the protocol-defined washout window.
* Pregnancy or breastfeeding.
* Known severe hypersensitivity to fludarabine, cyclophosphamide, or cell-product excipients.
* Any medical, psychiatric, or social condition that, in the investigator's judgment, would compromise safety, protocol compliance, or informed consent.

Conditions3

Interventions3

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