Head and Neck CancerPhase 1/2NCT04247282
Anti-PD-L1/TGF-beta Trap (M7824) Alone and in Combination With TriAd Vaccine and N-803 for Resectable Head and Neck Squamous Cell Carcinoma Not Associated With Human Papillomavirus Infection
A Phase 1/2 study testing M7824, N803 and TriAd vaccine in people with Head and Neck Cancer and Head and Neck Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Some people who get head and neck cancer will need surgery to treat their cancer. Research suggests that immunotherapy drugs may help fight head and neck cancer if given before surgery. In most cases, there is enough time between cancer diagnosis and surgery to test immunotherapy drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Neoplasms
- What is being tested?
- M7824, N803 and TriAd vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jun 2020to 12 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have histologically or cytologically confirmed, previously untreated intermediate/high risk, p16-negative (if oropharyngeal primary tumor), squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV).
- Male or female; Age greater than or equal to 18 years.
- Eastern Cooperative Oncology Group (ECOG performance status less than or equal to 1.
- Prothrombin time (PT) and partial thromboplastin time (PTT) within normal institutional limits. Patients with prolonged PTT determined to be due to lupus anticoagulant will not be excluded.
- Patients must have adequate organ and marrow function as defined below:
- Absolute neutrophil count greater than or equal to 1000/mcL
Show all 14Show fewer
- Platelets greater than or equal to 100,000/mcL
- Hemoglobin greater than or equal to 10.0 g/dL
- Total bilirubin within normal institutional limits; in patients with Gilbert's, less than or equal to 3.0 mg/dL
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to 3X upper limit of normal.
- Creatinine within 1.5X upper limit of normal institutional limits
- The effects of M7824, TriAd Vaccines (ETBX-011, ETBX-051 \& ETBX-061), and Anktiva (N-803) on the developing human fetus are unknown. For this reason, men and women of child-bearing capacity must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study and maintain such contraception until 2 months following the last dose of any study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Ability of subject to understand and the willingness to sign a written informed consent document
- Patients with successfully treated hepatitis C virus (HCV) are eligible if HCV viral load is undetectable.
Who cannot join
- Patients who are immunocompromised as follows:
- Human immunodeficiency virus (HIV) positive patients not on or not compliant with appropriate anti-retroviral therapy, patients with newly diagnosed (i.e., < 6 months) HIV, patients with an HIV viral load exceeding 400 copies/mL, HIV+ patients with a cluster of differentiation 4 (CD4) count < 150 cells/L, and HIV+ patients on antiretroviral therapy < 1 month are excluded. HIV-positive patients will also be excluded if the principal investigator (PI) determines that there is a clinically significant drug-drug interaction.
- Chronic administration (defined as daily or every other day for continued use >14 days) of systemic corticosteroids or other immune suppressive drugs, within 14 days before treatment on study. Physiologic daily dosing of steroids is allowed. Nasal, or inhaled steroid, topical steroid creams and eye drops for small body areas are allowed.
- Patients who have undergone allogeneic peripheral stem cell transplantation, or solid organ transplantation requiring immunosuppression
- Pregnant women are excluded from this study because M7824 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 breastfeeding should be discontinued if the mother is treated with M7824. These potential risks may also apply to other agents used in this study.
- Patients with active systemic autoimmune disease, except patients with type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring current immunosuppression, or with other endocrine disorders on replacement hormones, are not excluded if the condition is well controlled.
Show all 18Show fewer
- Patients with a history of inflammatory bowel disease
- Patients with a history inflammatory lung disease/interstitial lung disease/pulmonary fibrosis will be excluded. Patients with clinical findings (e.g., imaging) that are suggestive of inflammatory lung disease even if not experiencing symptoms of the disorder.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents to be used in the cohort the subject will be enrolled into.
- Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin). Patients enrolling on the M7824 only arm will be exempt from this exclusion.
- Patients with a history of bleeding diathesis or recent clinically significant bleeding events considered by the Investigator as high risk for investigational drug treatment are excluded.
- Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints.
- Patients with prior live vaccine, investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to enrollment. Locally approved coronavirus disease (COVID) vaccines are permitted.
- Uncontrolled intercurrent acute or chronic illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (>New York Heart Association Class I), hepatic disease, unstable angina pectoris, serious cardiac arrhythmia, requiring medication, uncontrolled hypertension (systolic blood pressure (SBP>170/ diastolic blood pressure (DBP>105) or psychiatric illness/social situations within 12 months that would limit compliance with study requirements.
- Patients who have undergone major surgery within 4 weeks prior to enrollment. A biopsy will not preclude a patient from starting study.
- Patients with a history of hepatitis B (HBV) are excluded due to potential risk for viral reactivation and resulting liver injury in persons with latent HBV.
- Patients with treated or active brain metastases are not eligible because we are enrolling non-metastatic head and neck cancer patients in this trial. Standard of care treatment is different for head and neck cancer patients with and without metastatic disease.
- Subjects unwilling to accept blood products as medically indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Sequential Window of Opportunity Trial of Anti-PD-L1/TGF-beta Trap (M7824 ) Alone and in Combination With TriAd Vaccine, and N-803 for Resectable Head and Neck Squamous Cell Carcinoma Not Associated With Human Papillomavirus Infection.
Background:
Some people who get head and neck cancer will need surgery to treat their cancer. Research suggests that immunotherapy drugs may help fight head and neck cancer if given before surgery. In most cases, there is enough time between cancer diagnosis and surgery to test immunotherapy drugs. In this study, researchers are testing the safety and anti-cancer abilities of 3 drugs given before surgery for head and neck cancer.
Read more
Objective:
To learn if giving M7824 alone, or with the TriAd Vaccine (ETBX-011, ETBX-051 \& ETBX-061), or with TriAd vaccine plus Anktiva (N-803) can shrink previously untreated head and neck tumors before surgery or stop the tumors from coming back after all treatment.
Eligibility:
People age 18 and older who have a head and neck cancer that has not been treated before, and the tumor must be removed with surgery.
Design:
Participants will be screened in a separate protocol.
Participants will have the following tests:
- medical history and physical exams
- computed tomography or magnetic resonance imaging scans
- tumor, mucosa, and skin biopsies
- electrocardiograms to monitor heart activity
- endoscopies (a tube is inserted through the nose to see the upper airway)
- blood and urine tests.
All participants will get bintrafusp alfa (M7824) through an intravenous infusion. For this, a small plastic tube is put into an arm vein. Some may also get the TriAd vaccine. It is injected under the skin on the arms or legs. Some may also get N-803. It is injected under the skin on the stomach.
Participants will have clinic visits while they are getting treatment and after treatment ends.
After treatment ends, participants will have their scheduled surgery. There will be two follow up visits at the National Institutes of Health (NIH) after your surgery. They will be contacted by phone or email every 2 weeks for 3 months. Then they will be contacted every 3 months for 2 years.
...
Read the detailed description
Background:
- Approximately 50% of patients with advanced, non-human papilloma virus (HPV) associated head and neck squamous cell carcinoma (HNSCC) will develop locoregional or distant relapse within two years of completing definitive standard-of-care treatment.
- Two ongoing clinical trials investigating neoadjuvant programmed cell death protein 1 (PD-1) blockade before surgical resection of HNSCC suggest that immunotherapy can both cytoreduce existing disease before surgery and reduce the risk of locoregional or distant disease relapse after surgery.
- Preliminary data from these studies suggest neoadjuvant treatments can be administered without delaying planned surgical intervention.
- Experiments conducted by the Laboratory of Tumor Immunology and Biology (LTIB) demonstrated synergistic activity with tumor-targeted adenoviral vaccine plus bintrafusp alfa (M7824) plus Anktiva (N-803) in humanized mice bearing human carcinomas and in vitro studies.
- M7824 is a bifunctional fusion protein consisting of an anti-programmed death ligand 1(PD-L1) antibody and the extracellular domain of transforming growth factor beta (TGF-beta) receptor type 2, a TGF-beta trap.
- Adenoviral vaccines targeting known shared tumor antigens can generate antigen-specific T cells.
- N-803 is an interleukin 15 (IL-15)/interleukin 15 receptor (IL-15R) alpha super agonist complex that can enhance both natural killer (NK) cell and T cell anti-tumor activity via expansion and activation.
- Activity observed with neoadjuvant anti-PD-1 agents alone provides rationale for testing of M7824 alone and in combination with other immune-oncologic agents that have been shown to work in concert with M7824 in preclinical studies.
- Analysis of pre- and post-treatment tissues from HNSCC patients presents a unique opportunity to interrogate the effects the above treatment(s) on tumor.
- A dose escalation of N-803 in combination with a flat dose of M7824 was conducted at the National Cancer Institute. Thirteen patients have been treated with the combination. No dose limiting toxicities (DLTs) were observed.
Objectives:
-Determine the rate of pathologic complete response (pCR) or clinical-to-pathological downstaging in patients with previously untreated intermediate/high risk, non-HPV associated, squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV) who receive any of the three proposed treatments: M7824 alone, M7824 plus TriAd vaccine, or M7824 plus TriAd vaccine plus N803 prior to definite surgery.
Eligibility:
- Patients must have histologically or cytologically confirmed, previously untreated intermediate/high risk, p16-negative (if oropharyngeal), squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV)
- Men or Women; Age greater than or equal to 18 years
- Eastern Cooperative Oncology Office (ECOG) performance status less than or equal to 1
Design:
- This protocol is a sequential window of opportunity trial of Anti-PD-L1/TGF-beta trap (M7824) alone and in combination with TriAd Vaccine (ETBX-011, ETBX-051 \& ETBX-061) and N-803 for non-HPV associated resectable Head and Neck Squamous Cell Carcinoma (HNSCC).
- Patients will be referred to the National Institutes of Health (NIH) for this immunotherapy treatment from surrounding academic medical centers and private physicians.
- Upon referral to the NIH, patients will be rapidly screened, and enrolled on the protocol, if appropriate.
- This trial will enroll patients in three arms sequentially to permit safety evaluation before adding the next agent.
- In the first arm of 12 patients, M7824 (1200 mg) will be administered intravenously on day 1 and 15.
- If no safety concerns, accrual will proceed to the 2nd arm, and 12 patients will enroll with M7824 (1200mg; intravenous) treatment on day 1 and 15 and TriAd vaccine (5 x 10 (11) viral particles (VP; subcutaneous) treatment on day 1 only.
- If no safety concerns, accrual will proceed to the 3rd arm, and 12 patients will enroll with M7824 ((1200mg; intravenous) treatment on day 1 and 15 plus TriAd vaccine (5 x 10(11) VP; subcutaneous injection) and N-803 (15mcg/kg, subcutaneously) treatment on day 1.
- After obtaining pre-treatment biopsies, imaging and blood collection, patients will receive the neoadjuvant immunotherapy at the NIH Clinical Center.
- Patients will then be sent back to their referring providers for their definitive standard of care surgery and adjuvant therapy as indicated based upon pathologic analysis of the surgical specimen. National Cancer Institute (NCI) investigators will have no role in directing the ensuing standard of care surgeries performed at outside institutions.
- For consistency in pathologic analysis of resection specimens, tissue blocks and/or slides will be obtained from outside institutions and be reviewed by the NCI Laboratory of Pathology.
- It is expected that up to 20 patients may enroll in one year. Thus, with 3 arms of 12 patients apiece, up to 36 evaluable patients may enroll. Accrual is expected to be completed within 2 years.
- Conditions
- Head and Neck Cancer, Head and Neck Neoplasms
- Being tested
- M7824, N803, TriAd vaccine
- Keywords
- Immuno-oncology, Neoadjuvant Treatments, Non-HPV, Immunotherapy, Head and Neck Cancer
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M7824Drug
Also called bintrafusp alfa
M7824 (1200 mg) will be administered intravenously on day 1 and 15 to patients enrolled in arm 1-3 (all three arms).
N803Drug
Also called Anktiva
N-803 (15 mcg/kg, subcutaneously) will be given on day 1 to patients enrolled in arm 3.
TriAd vaccineBiological
Also called ETBX-011, ETBX-051 & ETBX-061
TriAd vaccine (5 x 10e(11) viral particles (VP); subcutaneous injection) will be given on day 1 to patients enrolled in arm 2 and arm 3
| Study group | Role | What they receive |
|---|---|---|
| Arm A, Cohort 1 Bintrafusp Alfa (M7824) (Days 1, 15) | Experimental | M7824 (Days 1, 15) Receives: Drug: M7824 |
| Arm B, Cohort 1 M7824 + TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061) (Day 1) | Experimental | M7824 + TriAd vaccine (ETBX-011, ETBX-051 and ETBX-061) (Days 1) Receives: Drug: M7824; Biological: TriAd vaccine |
| Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1) | Experimental | M7824 + TriAd vaccine (Day 1) + N-803 (Day 1) Receives: Drug: M7824; Drug: N803; Biological: TriAd vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experience a Pathologic Complete Response (pCR)
Resected tumors were reviewed one month after being on study to determine a pCR, defined as absence of malignant cells in the resected tumor specimen. A pathologist examines tumor specimens to look for malignant cells.
Measured: Post treatment after on study, approximately one month
Number of Participants Who Experience Clinical to Pathologic Downstaging Upon Analysis of Resected Tumor After Completing Study Treatments
Clinical-to-pathologic downstaging is when the numerical pathological stage is lower than the initial numerical clinical stage (i.e., II to I)
Measured: up to 4 months after enrollment
Secondary outcomes (5)
Proportion of Participants With a Complete Response (CR) + Partial Response (PR) Measured by Computed Tomography (CT) Imaging and the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Response was measured by CT imaging and the RECIST to determine whose tumors shrunk after therapy. CR is disappearance of all target lesions, and PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: 21-28 days from enrollment, up to a maximum of 28 days
Number of Participants That Experienced Grade 3 or 4 Immune Related Adverse Events (irAEs)
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 3 is severe. Grade 4 is life-threatening. Permanent treatment discontinuation is required in some cases of immune-related Grade 4 AEs (e.g., Grade 4 rash/inflammatory dermatitis, nephritis,..). Permanent treatment discontinuation is not required when the AE is manifested by a single laboratory value out of normal range without any clinical correlates.
Measured: 2 weeks
Probability of Being Alive and Recurrence Free
Probability of being alive and recurrence (disease) free after treatment reported along with 95% confidence intervals. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Disease recurrence is defined as the cancer comes back evidenced by imaging, clinical exam and/or biopsy.
Measured: 1 and 2 years
Percentage of Participants Who Are Alive
Participants who are alive after therapy reported along with a 95% confidence interval.
Measured: Participants were followed to see if they were alive and recurrence free for up to 2 years from study enrollment.
Number of Participants With Treatment-related Adverse Events Causing a Delay of 4 Weeks or More Beyond Planned Surgery
Here is the number of participants with treatment-related adverse events causing a delay of 4 weeks or more beyond planned surgery. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 4 weeks or more beyond surgery, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2020
- Study start9 Jun 2020
- Primary completion24 Aug 2021
- Study completion12 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Hoyoung M. Maeng, M.D., National Cancer Institute (NCI)
- Investigators
- Hoyoung Maeng, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04247282
- Sponsor's protocol ID
- 200024
- Other IDs
- 20-C-0024
- Status last verified
- Jul 2025
- First submitted
- 25 Jan 2020
- Last updated
- 16 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All large- scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
Publications
Redman JM, Donahue RN, Steinberg SJ, Marte JL, Cordes L, Floudas CS, Prins D, Turkbey EB, Soon-Shiong P, Schlom J, Gulley JL, Allen CT. Tri-Ad5 vaccine plus bintrafusp alfa for newly diagnosed, advanced-stage head and neck cancer not associated with human papillomavirus infection. Oncologist. 2025 Mar 10;30(3):oyaf006. doi: 10.1093/oncolo/oyaf006.
PubMed 40156838Redman JM, Friedman J, Robbins Y, Sievers C, Yang X, Lassoued W, Sinkoe A, Papanicolau-Sengos A, Lee CC, Marte JL, Turkbey E, Mydlarz W, Joshi A, London NR Jr, Pierce M, Taylor R, Hong S, Nguyen A, Soon-Shiong P, Schlom J, Gulley JL, Allen CT. Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-beta blockade in HPV-unrelated head and neck cancer. J Clin Invest. 2022 Sep 15;132(18):e161400. doi: 10.1172/JCI161400.
PubMed 35727629Saint A, Van Obberghen-Schilling E. The role of the tumor matrix environment in progression of head and neck cancer. Curr Opin Oncol. 2021 May 1;33(3):168-174. doi: 10.1097/CCO.0000000000000730.
PubMed 33720067
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Sequential Window of Opportunity Trial of Anti-PD-L1/TGF-beta Trap (M7824 ) Alone and in Combination With TriAd Vaccine, and N-803 for Resectable Head and Neck Squamous Cell Carcinoma Not Associated With Human Papillomavirus Infection.
- ClinicalTrials.gov ID
- NCT04247282
- Acronym / sponsor ID
- 200024
- Conditions
- Head and Neck Cancer, Head and Neck Neoplasms
- Keywords
- Immuno-oncology, Neoadjuvant Treatments, Non-HPV, Immunotherapy, Head and Neck Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 9 Jun 2020 (actual)
- Primary completion
- 24 Aug 2021 (actual)
- Study completion
- 12 Jun 2023 (actual)
- First posted
- 30 Jan 2020 (actual)
- Results
- Posted 8 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Some people who get head and neck cancer will need surgery to treat their cancer. Research suggests that immunotherapy drugs may help fight head and neck cancer if given before surgery. In most cases, there is enough time between cancer diagnosis and surgery to test immunotherapy drugs. In this study, researchers are testing the safety and anti-cancer abilities of 3 drugs given before surgery for head and neck cancer.
Objective:
To learn if giving M7824 alone, or with the TriAd Vaccine (ETBX-011, ETBX-051 \& ETBX-061), or with TriAd vaccine plus Anktiva (N-803) can shrink previously untreated head and neck tumors before surgery or stop the tumors from coming back after all treatment.
Eligibility:
People age 18 and older who have a head and neck cancer that has not been treated before, and the tumor must be removed with surgery.
Design:
Participants will be screened in a separate protocol.
Participants will have the following tests:
- medical history and physical exams
- computed tomography or magnetic resonance imaging scans
- tumor, mucosa, and skin biopsies
- electrocardiograms to monitor heart activity
- endoscopies (a tube is inserted through the nose to see the upper airway)
- blood and urine tests.
All participants will get bintrafusp alfa (M7824) through an intravenous infusion. For this, a small plastic tube is put into an arm vein. Some may also get the TriAd vaccine. It is injected under the skin on the arms or legs. Some may also get N-803. It is injected under the skin on the stomach.
Participants will have clinic visits while they are getting treatment and after treatment ends.
After treatment ends, participants will have their scheduled surgery. There will be two follow up visits at the National Institutes of Health (NIH) after your surgery. They will be contacted by phone or email every 2 weeks for 3 months. Then they will be contacted every 3 months for 2 years.
...
Detailed description
Background:
- Approximately 50% of patients with advanced, non-human papilloma virus (HPV) associated head and neck squamous cell carcinoma (HNSCC) will develop locoregional or distant relapse within two years of completing definitive standard-of-care treatment.
- Two ongoing clinical trials investigating neoadjuvant programmed cell death protein 1 (PD-1) blockade before surgical resection of HNSCC suggest that immunotherapy can both cytoreduce existing disease before surgery and reduce the risk of locoregional or distant disease relapse after surgery.
- Preliminary data from these studies suggest neoadjuvant treatments can be administered without delaying planned surgical intervention.
- Experiments conducted by the Laboratory of Tumor Immunology and Biology (LTIB) demonstrated synergistic activity with tumor-targeted adenoviral vaccine plus bintrafusp alfa (M7824) plus Anktiva (N-803) in humanized mice bearing human carcinomas and in vitro studies.
- M7824 is a bifunctional fusion protein consisting of an anti-programmed death ligand 1(PD-L1) antibody and the extracellular domain of transforming growth factor beta (TGF-beta) receptor type 2, a TGF-beta trap.
- Adenoviral vaccines targeting known shared tumor antigens can generate antigen-specific T cells.
- N-803 is an interleukin 15 (IL-15)/interleukin 15 receptor (IL-15R) alpha super agonist complex that can enhance both natural killer (NK) cell and T cell anti-tumor activity via expansion and activation.
- Activity observed with neoadjuvant anti-PD-1 agents alone provides rationale for testing of M7824 alone and in combination with other immune-oncologic agents that have been shown to work in concert with M7824 in preclinical studies.
- Analysis of pre- and post-treatment tissues from HNSCC patients presents a unique opportunity to interrogate the effects the above treatment(s) on tumor.
- A dose escalation of N-803 in combination with a flat dose of M7824 was conducted at the National Cancer Institute. Thirteen patients have been treated with the combination. No dose limiting toxicities (DLTs) were observed.
Objectives:
-Determine the rate of pathologic complete response (pCR) or clinical-to-pathological downstaging in patients with previously untreated intermediate/high risk, non-HPV associated, squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV) who receive any of the three proposed treatments: M7824 alone, M7824 plus TriAd vaccine, or M7824 plus TriAd vaccine plus N803 prior to definite surgery.
Eligibility:
- Patients must have histologically or cytologically confirmed, previously untreated intermediate/high risk, p16-negative (if oropharyngeal), squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV)
- Men or Women; Age greater than or equal to 18 years
- Eastern Cooperative Oncology Office (ECOG) performance status less than or equal to 1
Design:
- This protocol is a sequential window of opportunity trial of Anti-PD-L1/TGF-beta trap (M7824) alone and in combination with TriAd Vaccine (ETBX-011, ETBX-051 \& ETBX-061) and N-803 for non-HPV associated resectable Head and Neck Squamous Cell Carcinoma (HNSCC).
- Patients will be referred to the National Institutes of Health (NIH) for this immunotherapy treatment from surrounding academic medical centers and private physicians.
- Upon referral to the NIH, patients will be rapidly screened, and enrolled on the protocol, if appropriate.
- This trial will enroll patients in three arms sequentially to permit safety evaluation before adding the next agent.
- In the first arm of 12 patients, M7824 (1200 mg) will be administered intravenously on day 1 and 15.
- If no safety concerns, accrual will proceed to the 2nd arm, and 12 patients will enroll with M7824 (1200mg; intravenous) treatment on day 1 and 15 and TriAd vaccine (5 x 10 (11) viral particles (VP; subcutaneous) treatment on day 1 only.
- If no safety concerns, accrual will proceed to the 3rd arm, and 12 patients will enroll with M7824 ((1200mg; intravenous) treatment on day 1 and 15 plus TriAd vaccine (5 x 10(11) VP; subcutaneous injection) and N-803 (15mcg/kg, subcutaneously) treatment on day 1.
- After obtaining pre-treatment biopsies, imaging and blood collection, patients will receive the neoadjuvant immunotherapy at the NIH Clinical Center.
- Patients will then be sent back to their referring providers for their definitive standard of care surgery and adjuvant therapy as indicated based upon pathologic analysis of the surgical specimen. National Cancer Institute (NCI) investigators will have no role in directing the ensuing standard of care surgeries performed at outside institutions.
- For consistency in pathologic analysis of resection specimens, tissue blocks and/or slides will be obtained from outside institutions and be reviewed by the NCI Laboratory of Pathology.
- It is expected that up to 20 patients may enroll in one year. Thus, with 3 arms of 12 patients apiece, up to 36 evaluable patients may enroll. Accrual is expected to be completed within 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A, Cohort 1 Bintrafusp Alfa (M7824) (Days 1, 15) | Experimental | Drug: M7824M7824 (Days 1, 15) |
| Arm B, Cohort 1 M7824 + TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061) (Day 1) | Experimental | Drug: M7824, Biological: TriAd vaccineM7824 + TriAd vaccine (ETBX-011, ETBX-051 and ETBX-061) (Days 1) |
| Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1) | Experimental | Drug: M7824, Drug: N803, Biological: TriAd vaccineM7824 + TriAd vaccine (Day 1) + N-803 (Day 1) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have histologically or cytologically confirmed, previously untreated intermediate/high risk, p16-negative (if oropharyngeal primary tumor), squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV).
- Male or female; Age greater than or equal to 18 years.
- Eastern Cooperative Oncology Group (ECOG performance status less than or equal to 1.
- Prothrombin time (PT) and partial thromboplastin time (PTT) within normal institutional limits. Patients with prolonged PTT determined to be due to lupus anticoagulant will not be excluded.
- Patients must have adequate organ and marrow function as defined below:
Key exclusion criteria (18 listed)
- Patients who are immunocompromised as follows:
- Pregnant women are excluded from this study because M7824 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 breastfeeding should be discontinued if the mother is treated with M7824. These potential risks may also apply to other agents used in this study.
- Patients with active systemic autoimmune disease, except patients with type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring current immunosuppression, or with other endocrine disorders on replacement hormones, are not excluded if the condition is well controlled.
- Patients with a history of inflammatory bowel disease
- Patients with a history inflammatory lung disease/interstitial lung disease/pulmonary fibrosis will be excluded. Patients with clinical findings (e.g., imaging) that are suggestive of inflammatory lung disease even if not experiencing symptoms of the disorder.
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 |
|---|---|---|
| M7824Also: bintrafusp alfaM7824 (1200 mg) will be administered intravenously on day 1 and 15 to patients enrolled in arm 1-3 (all three arms). | Drug | Arm A, Cohort 1 Bintrafusp Alfa (M7824) (Days 1, 15), Arm B, Cohort 1 M7824 + TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061) (Day 1), Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1) |
| N803Also: AnktivaN-803 (15 mcg/kg, subcutaneously) will be given on day 1 to patients enrolled in arm 3. | Drug | Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1) |
| TriAd vaccineAlso: ETBX-011, ETBX-051 & ETBX-061TriAd vaccine (5 x 10e(11) viral particles (VP); subcutaneous injection) will be given on day 1 to patients enrolled in arm 2 and arm 3 | Biological | Arm B, Cohort 1 M7824 + TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061) (Day 1), Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1) |
Primary outcome
Number of Participants Who Experience a Pathologic Complete Response (pCR)
Time frame: Post treatment after on study, approximately one month
Resected tumors were reviewed one month after being on study to determine a pCR, defined as absence of malignant cells in the resected tumor specimen. A pathologist examines tumor specimens to look for malignant cells.
Number of Participants Who Experience Clinical to Pathologic Downstaging Upon Analysis of Resected Tumor After Completing Study Treatments
Time frame: up to 4 months after enrollment
Clinical-to-pathologic downstaging is when the numerical pathological stage is lower than the initial numerical clinical stage (i.e., II to I)
5 secondary outcomes
Proportion of Participants With a Complete Response (CR) + Partial Response (PR) Measured by Computed Tomography (CT) Imaging and the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: 21-28 days from enrollment, up to a maximum of 28 days
Number of Participants That Experienced Grade 3 or 4 Immune Related Adverse Events (irAEs)
Time frame: 2 weeks
Probability of Being Alive and Recurrence Free
Time frame: 1 and 2 years
Percentage of Participants Who Are Alive
Time frame: Participants were followed to see if they were alive and recurrence free for up to 2 years from study enrollment.
Number of Participants With Treatment-related Adverse Events Causing a Delay of 4 Weeks or More Beyond Planned Surgery
Time frame: 4 weeks or more beyond surgery, up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 40156838Redman JM, Donahue RN, Steinberg SJ, Marte JL, Cordes L, Floudas CS, Prins D, Turkbey EB, Soon-Shiong P, Schlom J, Gulley JL, Allen CT. Tri-Ad5 vaccine plus bintrafusp alfa for newly diagnosed, advanced-stage head and neck cancer not associated with human papillomavirus infection. Oncologist. 2025 Mar 10;30(3):oyaf006. doi: 10.1093/oncolo/oyaf006.
- Derived from this study: PubMed 35727629Redman JM, Friedman J, Robbins Y, Sievers C, Yang X, Lassoued W, Sinkoe A, Papanicolau-Sengos A, Lee CC, Marte JL, Turkbey E, Mydlarz W, Joshi A, London NR Jr, Pierce M, Taylor R, Hong S, Nguyen A, Soon-Shiong P, Schlom J, Gulley JL, Allen CT. Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-beta blockade in HPV-unrelated head and neck cancer. J Clin Invest. 2022 Sep 15;132(18):e161400. doi: 10.1172/JCI161400.
- Derived from this study: PubMed 33720067Saint A, Van Obberghen-Schilling E. The role of the tumor matrix environment in progression of head and neck cancer. Curr Opin Oncol. 2021 May 1;33(3):168-174. doi: 10.1097/CCO.0000000000000730.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All large- scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
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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.
Hoyoung Maeng, M.D. principal investigator
National Cancer Institute (NCI)
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 M7824, N803 and TriAd vaccine in people with Head and Neck Cancer and Head and Neck Neoplasms, run by National Cancer Institute (NCI) 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 14 inclusion and 18 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: finished, as of the sponsor's last update on 16 Jul 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 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?
Yes. Results are posted in the registry (first posted 8 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Who Experience a Pathologic Complete Response (pCR) (time frame: Post treatment after on study, approximately one month). 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?
On the ClinicalTrials.gov record for NCT04247282, which also lists 3 linked publications.
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 16 Jul 2025.