Head and Neck Squamous Cell CarcinomaPhase 1NCT06159621
CD40 Agonist and PD-1 Inhibitor in HNSCC
A Phase 1 study testing PD-1inhibitor - LVGN 3616 and CD 40 Agonist - LVGN 7409 in people with Head and Neck Squamous Cell Carcinoma, run by University of Pennsylvania at 1 site in United States.
Trial summary
Prospective, open-label, phase 1 study of CD40 agonist (LVGN7409) and PD-1 inhibition (LVGN3616 or nivolumab) in patients with resectable Human Papillomavirus (HPV)-negative mucosal head/neck squamous cell carcinoma (HNSCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- PD-1inhibitor - LVGN 3616 and CD 40 Agonist - LVGN 7409
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jul 2024to 1 Mar 2028
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Signed and dated written IRB-approved informed consent.
- 2. Age ≥18 years.
- 3. Body weight > 30kg
- 4. Human Papillomavirus (HPV)-negative histologically confirmed mucosal squamous cell head and neck cancer (oral cavity, oropharynx, larynx, hypopharynx) for which definitive surgery is planned. Sites other than oropharynx are assumed to be HPV negative unless specifically shown otherwise. Oropharynx HPV status can be determined through p16 or nucleic acid testing (ISH).
- 5. Tumor tissue sample (non-cytology specimen) available prior to Study Treatment, either via archived non-FNA (fine needle aspirate) tumor biopsy specimen or fresh biopsy
- 6. Life expectancy of at least 12 weeks.
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- 7. Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 /mm3, hemoglobin ≥9.0 g/dL, total serum bilirubin within 1.5 x upper limit of normal (ULN) unless Gilbert's, AST/ALT, within 2.5 x ULN, Albumin ≥3g/dL, and all tests performed within 4 weeks prior to administration of Study Treatment.
- 8. Eastern Cooperative Oncology Group (ECOG) with no clinically significant findings as assessed by the investigator.
- 9. ECOG performance status of 0-1.
- 10. Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after therapy). Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Female patients should also refrain from breastfeeding throughout this period.
- 11. Able and willing to comply with all study procedures.
Who cannot join
- 1. Prior history of Head and Neck Squamous Cell Carcinoma (HNSCC) for which patient has undergone surgery or radiation involving the current planned surgical site.
- 2. Known history of hepatitis B or C with active viral replication. 3. Administration of any live vaccine within 28 days of first dose of study treatment.
- 4. Prior anti-PD1 or CD40 agonist therapy. 5. Participation in another interventional clinical trial within 30 days before receiving first dose of study treatment. However, the subject may participate in observational studies.
- 6. Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.
- 7. Current or prior use of immunosuppressive medication within 14 days before study treatment. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
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- 8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product (IP).
- 9. History of allogenic organ transplantation 10. Active or prior documented autoimmune disease. Examples include inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or type 1 Diabetes Mellitus (DM) controlled with insulin.
- Any chronic skin condition that does not require systemic therapy.
- Patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician.
- Patients with celiac disease controlled by diet alone. 11. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 12. History of another active malignancy except for non-melanoma skin cancer, lentigo maligna or other carcinoma in situ 13. History of active primary immunodeficiency. Patients with Human Immunodeficiency Virus (HIV) with undetectable HIV viral loads by standard clinical assays are eligible.
- 14. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Neoadjuvant/Phase 1 Study of CD40 Agonist (LVGN7409) and PD-1 Inhibitor (LVGN3616) in Patients With Resectable HPV-negative Mucosal Head/Neck Squamous Cell Carcinoma (HNSCC)
Prospective, open-label, phase 1 study of CD40 agonist (LVGN7409) and PD-1 inhibition (LVGN3616 or nivolumab) in patients with resectable Human Papillomavirus (HPV)-negative mucosal head/neck squamous cell carcinoma (HNSCC). This protocol proposes to study the safety and immunological effects of LVGN7409, a CD40 agonistic antibody, when administered in combination with PD-1 inhibition prior to surgical resection.
Read the detailed description
This will be a prospective, open-label, window of opportunity study of LVGN7409 and LVGN3616 (or nivolumab) in resectable HPV-negative HNSCC with co-primary endpoints of safety and T cell infiltration, and secondary endpoint of anti-tumor efficacy.
Doses of LVGN7409 and LVGN3616 (or nivolumab) are based on safety experience in prior and ongoing clinical trials. Dose escalation will not be conducted in this trial. The study is divided into the following treatment cohorts:
- Arm A: PD1 [LVGN3616 (300mg) or nivolumab (240mg)] II. Arm B: PD1 [LVGN3616 (300mg) or nivolumab (240mg)] + CD40 [LVGN7409 (1mg/kg)]
Pre-Surgery and Surgery
- Patients with potentially resectable HPV-negative HNSCC will be identified by H\&N surgeons and study coordinator (clinic screening). Consent and enrollment will take place in H\&N Surgery clinic by study investigators and/or the study coordinator.
- Patients will need baseline non-Fine needle aspirate (FNA) tumor biopsy, either during standard of care exam under anesthesia (EUA) or via ultrasound-guided needle biopsy (prior archival non-FNA biopsy is acceptable as long as obtained within 6 months of screening).
- Patients will be assigned in an alternating fashion to Arm A (PD1) or Arm B (PD1+CD40). At a separate infusion visit after enrollment, patients in arm A or arm B will receive a single administration of LVGN3616 (or nivolumab) or LVGN3616 (or nivolumab) and LVGN7409, respectively. In case of patient drop-out after screening/consent and before drug administration, that slot will be assigned to the next available patient.
- Patients will be included in the primary endpoint calculations (safety) if they receive study drug. However, any patients unable to undergo planned surgery within 6 weeks will not contribute to the post-treatment immunologic sample analysis and this slot will be filled by a subsequent patient in order to achieve the goal of 10 paired samples in each arm. The maximum number of patients that can be replaced is 5.
- After ~2 weeks (allowable range 6-42 days), patients will undergo planned surgical resection. Repeat imaging is not required.
- Blood collection will occur on the day of drug administration prior to administration, 24-48 hours after administration, 1 week (+/-1 day) after administration, and on day of planned surgery. In person blood draws (D1, D7, etc.) can be waived in cases of transportation or logistical burden to the patient, at the discretion of the investigator.
Post-Surgery
- Guideline-based standard of care post-surgical adjuvant therapies, as indicated based on pathological features on surgical resection, will occur as part of routine clinical care.
- Post-operative visits will occur every 3 months (+/-4 weeks) after surgery up to 1 year, which will serve as End of trial (EOT) visit and final Adverse Event (AE) assessment. The following will be performed during each of these visits:
- Physical exam
- Laboratory monitoring
- AE assessment
- Concomitant medication review
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- PD-1inhibitor - LVGN 3616, CD 40 Agonist - LVGN 7409
- Medical subject headings
- 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.
PD-1inhibitor - LVGN 3616Drug
Administration of one dose of LVGN 3616 - 300mg. Commercially available PD-1 inhibitor may be substituted.
CD 40 Agonist - LVGN 7409Drug
Administration of one dose of LVGN 7409 - 1mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Arm A: PD1 | Active comparator | Not described Receives: Drug: PD-1inhibitor - LVGN 3616 |
| Arm B: PD1 + CD40 | Active comparator | Not described Receives: Drug: PD-1inhibitor - LVGN 3616; Drug: CD 40 Agonist - LVGN 7409 |
What is being measured
The primary outcome is the main question the study is designed to answer.
T cell frequency pre-treatment, as measured by immunohistochemistry (IHC) for CD8 on pre-treatment biopsy and resection tissue compared to T cell frequency post-treatment as measured by IHC for CD8 on biopsy and resection tissue post-treatment.
Measured: 1 year
Number of participants who undergo planned surgery within 6 weeks after drug administration
Measured: 6 weeks
Secondary outcomes (3)
Pathological Response
Defined as the Percentage of the decrease in tumor resection bed replaced by necrotic tumor, histiocytes/giant cells fibrosis, and/or keratinous debris. Grading:
- PTR0, <10% pathologic response
- PTR1, 10%-49% pathologic response
- PTR2, ≥50% pathologic response
Measured: 6 weeks
Event free survival
Measured: 3 years
Progression free survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start2 Jul 2024
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be assigned in an alternating fashion to Arm A (PD1 - LVGN 3616) or Arm B (PD1 LVGN 3616)+CD40 (LVGN 7409)). At a separate infusion visit after enrollment, patients in arm A or arm B will receive a single administration of LVGN3616 (300 mg.) or LVGN3616 (300 mg.) and LVGN7409 (1mg/kg), respectively. In case of patient drop-out after screening/consent and before drug administration, that slot will be assigned to the next available patient
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06159621
- Sponsor's protocol ID
- IRB 855063
- Status last verified
- Nov 2025
- First submitted
- 16 Nov 2023
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: No plan is in place
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant/Phase 1 Study of CD40 Agonist (LVGN7409) and PD-1 Inhibitor (LVGN3616) in Patients With Resectable HPV-negative Mucosal Head/Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT06159621
- Acronym / sponsor ID
- IRB 855063
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 2 Jul 2024 (actual)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Mar 2028 (estimated)
- First posted
- 7 Dec 2023 (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.
Prospective, open-label, phase 1 study of CD40 agonist (LVGN7409) and PD-1 inhibition (LVGN3616 or nivolumab) in patients with resectable Human Papillomavirus (HPV)-negative mucosal head/neck squamous cell carcinoma (HNSCC). This protocol proposes to study the safety and immunological effects of LVGN7409, a CD40 agonistic antibody, when administered in combination with PD-1 inhibition prior to surgical resection.
Detailed description
This will be a prospective, open-label, window of opportunity study of LVGN7409 and LVGN3616 (or nivolumab) in resectable HPV-negative HNSCC with co-primary endpoints of safety and T cell infiltration, and secondary endpoint of anti-tumor efficacy.
Doses of LVGN7409 and LVGN3616 (or nivolumab) are based on safety experience in prior and ongoing clinical trials. Dose escalation will not be conducted in this trial. The study is divided into the following treatment cohorts:
- Arm A: PD1 [LVGN3616 (300mg) or nivolumab (240mg)] II. Arm B: PD1 [LVGN3616 (300mg) or nivolumab (240mg)] + CD40 [LVGN7409 (1mg/kg)]
Pre-Surgery and Surgery
- Patients with potentially resectable HPV-negative HNSCC will be identified by H\&N surgeons and study coordinator (clinic screening). Consent and enrollment will take place in H\&N Surgery clinic by study investigators and/or the study coordinator.
- Patients will need baseline non-Fine needle aspirate (FNA) tumor biopsy, either during standard of care exam under anesthesia (EUA) or via ultrasound-guided needle biopsy (prior archival non-FNA biopsy is acceptable as long as obtained within 6 months of screening).
- Patients will be assigned in an alternating fashion to Arm A (PD1) or Arm B (PD1+CD40). At a separate infusion visit after enrollment, patients in arm A or arm B will receive a single administration of LVGN3616 (or nivolumab) or LVGN3616 (or nivolumab) and LVGN7409, respectively. In case of patient drop-out after screening/consent and before drug administration, that slot will be assigned to the next available patient.
- Patients will be included in the primary endpoint calculations (safety) if they receive study drug. However, any patients unable to undergo planned surgery within 6 weeks will not contribute to the post-treatment immunologic sample analysis and this slot will be filled by a subsequent patient in order to achieve the goal of 10 paired samples in each arm. The maximum number of patients that can be replaced is 5.
- After ~2 weeks (allowable range 6-42 days), patients will undergo planned surgical resection. Repeat imaging is not required.
- Blood collection will occur on the day of drug administration prior to administration, 24-48 hours after administration, 1 week (+/-1 day) after administration, and on day of planned surgery. In person blood draws (D1, D7, etc.) can be waived in cases of transportation or logistical burden to the patient, at the discretion of the investigator.
Post-Surgery
- Guideline-based standard of care post-surgical adjuvant therapies, as indicated based on pathological features on surgical resection, will occur as part of routine clinical care.
- Post-operative visits will occur every 3 months (+/-4 weeks) after surgery up to 1 year, which will serve as End of trial (EOT) visit and final Adverse Event (AE) assessment. The following will be performed during each of these visits:
- Physical exam
- Laboratory monitoring
- AE assessment
- Concomitant medication review
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be assigned in an alternating fashion to Arm A (PD1 - LVGN 3616) or Arm B (PD1 LVGN 3616)+CD40 (LVGN 7409)). At a separate infusion visit after enrollment, patients in arm A or arm B will receive a single administration of LVGN3616 (300 mg.) or LVGN3616 (300 mg.) and LVGN7409 (1mg/kg), respectively. In case of patient drop-out after screening/consent and before drug administration, that slot will be assigned to the next available patient
| Arm | Type | Receives |
|---|---|---|
| Arm A: PD1 | Active comparator | Drug: PD-1inhibitor - LVGN 3616 |
| Arm B: PD1 + CD40 | Active comparator | Drug: PD-1inhibitor - LVGN 3616, Drug: CD 40 Agonist - LVGN 7409 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1. Signed and dated written IRB-approved informed consent.
- 2. Age ≥18 years.
- 3. Body weight > 30kg
- 4. Human Papillomavirus (HPV)-negative histologically confirmed mucosal squamous cell head and neck cancer (oral cavity, oropharynx, larynx, hypopharynx) for which definitive surgery is planned. Sites other than oropharynx are assumed to be HPV negative unless specifically shown otherwise. Oropharynx HPV status can be determined through p16 or nucleic acid testing (ISH).
- 5. Tumor tissue sample (non-cytology specimen) available prior to Study Treatment, either via archived non-FNA (fine needle aspirate) tumor biopsy specimen or fresh biopsy
Key exclusion criteria (14 listed)
- 1. Prior history of Head and Neck Squamous Cell Carcinoma (HNSCC) for which patient has undergone surgery or radiation involving the current planned surgical site.
- 2. Known history of hepatitis B or C with active viral replication. 3. Administration of any live vaccine within 28 days of first dose of study treatment.
- 4. Prior anti-PD1 or CD40 agonist therapy. 5. Participation in another interventional clinical trial within 30 days before receiving first dose of study treatment. However, the subject may participate in observational studies.
- 6. Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.
- 7. Current or prior use of immunosuppressive medication within 14 days before study treatment. The following are exceptions to this criterion:
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 |
|---|---|---|
| PD-1inhibitor - LVGN 3616Administration of one dose of LVGN 3616 - 300mg. Commercially available PD-1 inhibitor may be substituted. | Drug | Arm A: PD1, Arm B: PD1 + CD40 |
| CD 40 Agonist - LVGN 7409Administration of one dose of LVGN 7409 - 1mg/kg | Drug | Arm B: PD1 + CD40 |
Primary outcome
T cell frequency pre-treatment, as measured by immunohistochemistry (IHC) for CD8 on pre-treatment biopsy and resection tissue compared to T cell frequency post-treatment as measured by IHC for CD8 on biopsy and resection tissue post-treatment.
Time frame: 1 year
Number of participants who undergo planned surgery within 6 weeks after drug administration
Time frame: 6 weeks
3 secondary outcomes
Pathological Response
Time frame: 6 weeks
Event free survival
Time frame: 3 years
Progression free survival
Time frame: 3 years
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 3 Dec 2025.
- Individual participant dataSharing planned: Undecided. No plan is in place
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PD-1inhibitor - LVGN 3616 and CD 40 Agonist - LVGN 7409 in people with Head and Neck Squamous Cell Carcinoma, run by University of Pennsylvania at 1 site in United States.
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 14 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: under way, not looking for participants, as of the sponsor's last update on 3 Dec 2025. 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 United States. 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 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T cell frequency pre-treatment, as measured by immunohistochemistry (IHC) for CD8 on pre-treatment biopsy and resection tissue compared to T cell frequency post-treatment as measured by IHC for CD8 on biopsy and resection tissue post-treatment. (time frame: 1 year). 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 3 Dec 2025.