EGFR/HER2 Dual-Target CAR-NK Cells for Recurrent or Metastatic HNSCC (DUAL-HN)

May 25, 2026 updated by: Beijing Biotech

A Phase 1/2, Open-Label, Biomarker-Enriched Study of Allogeneic EGFR/HER2 Dual-Target CAR-NK Cells Following Fludarabine/Cyclophosphamide Lymphodepletion in Adults With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

  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

Enrollment (Estimated)

42

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EGFR/HER2 Dual-Target CAR-NK After Flu/Cy
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
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
Drug: Fludarabine
Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
Drug: Cyclophosphamide
Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 Days
28 Days
Determination of the recommended Phase 2 dose
Time Frame: By completion of Part A
By completion of Part A

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease control rate (DCR)
Time Frame: 12 months
12 months
Incidence of treatment-emergent adverse events
Time Frame: 12 months
12 months
Objective response rate (ORR) by RECIST 1.1
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

May 17, 2028

Study Registration Dates

First Submitted

May 25, 2026

First Submitted That Met QC Criteria

May 25, 2026

First Posted (Actual)

June 1, 2026

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 25, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESBI202571-118

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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