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).
1. Adults with recurrent or metastatic HNSCC that is not amenable to curative surgery or radiotherapy will undergo central biomarker assessment using archival and/or fresh tumor tissue. Mandatory enrollment biomarkers for this example are EGFR and HER2/ERBB2. CD70 expression will be collected as an exploratory biomarker and may guide future cohort amendments. 2. Eligible participants will receive lymphodepleting fludarabine and cyclophosphamide on Days -5 to -3, followed by infusion of allogeneic EGFR/HER2 dual-target CAR-NK cells on Days 0, 7, and 14. The investigational product in this example is assumed to include membrane-bound IL-15 to support persistence and an inducible caspase-9 safety switch for controllability. 3. Part A uses a modified 3+3 dose-escalation design to identify the maximum tolerated dose , dose-limiting toxicities (DLTs), and the RP2D / recommended schedule. Part B is a biomarker-enriched expansion cohort treated at the RP2D to estimate objective response rate and durability of disease control. 4. An optional second cycle after Day 28 may be permitted for participants with stable disease or objective response and without prohibitive toxicity. Serial blood, ctDNA, immune profiling, and optional on-treatment biopsy samples will be collected to study CAR-NK expansion, persistence, antigen modulation, and resistance pathways.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Allogeneic 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
Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGIncidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Determination of the recommended Phase 2 dose
Time frame: By completion of Part A
Incidence of treatment-emergent adverse events
Time frame: 12 months
Objective response rate (ORR) by RECIST 1.1
Time frame: 12 months
Disease control rate (DCR)
Time frame: 12 months
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