Recurrent or Metastatic Head and Neck Squamous Cell CarcinomaPhase 1/2DUAL-HNNCT07617805
EGFR/HER2 Dual-Target CAR-NK Cells for Recurrent or Metastatic HNSCC
A Phase 1/2 study testing EGFR/HER2 Dual-Target CAR-NK Cells, Fludarabine and Cyclophosphamide in people with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Biomarker-positive EGFR/HER2- Expressing HNSCC, run by Beijing Biotech at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma, Biomarker-positive EGFR/HER2- Expressing HNSCC
- What is being tested?
- EGFR/HER2 Dual-Target CAR-NK Cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2026to 17 May 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Zhen J Peng, Phd, +86 13076790039, Zhen-Peng@beijing-biotech.com
About this study
Official title: 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).
Read the detailed description
- 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.
- 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.
- 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.
- 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.
- Conditions
- Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma, Biomarker-positive EGFR/HER2- Expressing HNSCC
- Being tested
- EGFR/HER2 Dual-Target CAR-NK Cells, Fludarabine, Cyclophosphamide
- Keywords
- Solid tumor, Head and neck squamous cell carcinoma (HNSCC), CAR-NK, Adoptive cell therapy, Allogeneic NK cells, Biomarker-enriched, EGFR, HER2, ERBB2
- Medical subject headings
- Recurrence, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGFR/HER2 Dual-Target CAR-NK CellsBiological
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
FludarabineDrug
Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
CyclophosphamideDrug
Lymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: EGFR/HER2 Dual-Target CAR-NK Cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Measured: 28 Days
Determination of the recommended Phase 2 dose
Measured: By completion of Part A
Secondary outcomes (3)
Incidence of treatment-emergent adverse events
Measured: 12 months
Objective response rate (ORR) by RECIST 1.1
Measured: 12 months
Disease control rate (DCR)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2026
- Study start2 Mar 2026
- Primary completion14 Mar 2027 (estimated)
- Study completion17 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent or Metastatic Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Beijing BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07617805
- Sponsor's protocol ID
- ESBI202571-118
- Acronym
- DUAL-HN
- Status last verified
- May 2026
- First submitted
- 25 May 2026
- Last updated
- 1 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07617805
- Acronym / sponsor ID
- DUAL-HN / ESBI202571-118
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2026 (actual)
- Primary completion
- 14 Mar 2027 (estimated)
- Study completion
- 17 May 2028 (estimated)
- First posted
- 1 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
- 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.
- 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.
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| EGFR/HER2 Dual-Target CAR-NK After Flu/Cy | Experimental | Biological: EGFR/HER2 Dual-Target CAR-NK Cells, Drug: Fludarabine, Drug: CyclophosphamideParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EGFR/HER2 Dual-Target CAR-NK CellsAllogeneic 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 | Biological | EGFR/HER2 Dual-Target CAR-NK After Flu/Cy |
| FludarabineLymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule. | Drug | EGFR/HER2 Dual-Target CAR-NK After Flu/Cy |
| CyclophosphamideLymphodepleting chemotherapy administered before the first infusion according to protocol-defined dose and schedule. | Drug | EGFR/HER2 Dual-Target CAR-NK After Flu/Cy |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Determination of the recommended Phase 2 dose
Time frame: By completion of Part A
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EGFR/HER2 Dual-Target CAR-NK Cells, Fludarabine and Cyclophosphamide in people with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Biomarker-positive EGFR/HER2- Expressing HNSCC, run by Beijing Biotech at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact shan S Lu, Phd (+86 13076790030, Seni-Lu@beijing-biotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.