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

NCT07617805 | Recruiting Phase 1

• 1 other identifier: ESBI202571-118
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma; Biomarker-positive EGFR/HER2- Expressing HNSCC

Keywords

Solid tumor; Head and neck squamous cell carcinoma (HNSCC); CAR-NK; Adoptive cell therapy; Allogeneic NK cells; Biomarker-enriched; EGFR; HER2; ERBB2

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  28 Days

• Determination of the recommended Phase 2 dose

  By completion of Part A

Secondary Outcomes (3)

• Incidence of treatment-emergent adverse events

  12 months

• Objective response rate (ORR) by RECIST 1.1

  12 months

• Disease control rate (DCR)

  12 months

Study Arms (1)

EGFR/HER2 Dual-Target CAR-NK After Flu/Cy

EXPERIMENTAL

Participants receive fludarabine and cyclophosphamide lymphodepletion on Days -5 to -3, followed by EGFR/HER2 dual-target CAR-NK cell infusions on Days 0, 7, and 14. A second cycle may be allowed after Day 28 in selected participants with ongoing benefit and acceptable toxicity.

Biological: EGFR/HER2 Dual-Target CAR-NK Cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

EGFR/HER2 Dual-Target CAR-NK Cells BIOLOGICAL

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

EGFR/HER2 Dual-Target CAR-NK After Flu/Cy

Fludarabine DRUG

Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.

EGFR/HER2 Dual-Target CAR-NK After Flu/Cy

Cyclophosphamide DRUG

Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.

EGFR/HER2 Dual-Target CAR-NK After Flu/Cy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Squamous Cell Carcinoma of Head and Neck

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

shan S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-label conduct is appropriate for a first-in-population cellular therapy where real-time safety review, biomarker confirmation, and infusion logistics are central to trial execution.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All enrolled participants receive fludarabine / cyclophosphamide lymphodepletion followed by EGFR/HER2 dual-target CAR-NK cells. Part A is a modified 3+3 dose-escalation safety lead-in. Part B is an expansion cohort treated at the RP2D.

Study Record Dates

• First Submitted: May 25, 2026
• First Posted: June 1, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): May 17, 2028
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

CN (1)