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

NCT04247282 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20002420-C-0024
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 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. ...

Conditions

Head and Neck Cancer; Head and Neck Neoplasms

Keywords

Immuno-oncology; Neoadjuvant Treatments; Non-HPV; Immunotherapy; Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

  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

  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)

  2 weeks

• Probability of Being Alive and Recurrence Free

  1 and 2 years

• Percentage of Participants Who Are Alive

  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

  4 weeks or more beyond surgery, up to 2 years

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, approximately 2 years and 12 days for Arm A, and 2 months and 29 days for Arm B.

Study Arms (3)

Arm A, Cohort 1 Bintrafusp Alfa (M7824) (Days 1, 15)

EXPERIMENTAL

M7824 (Days 1, 15)

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)

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)

Drug: M7824; Drug: N803; Biological: TriAd vaccine

Interventions

M7824 DRUG

M7824 (1200 mg) will be administered intravenously on day 1 and 15 to patients enrolled in arm 1-3 (all three arms).

Also known as: bintrafusp alfa

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)

N803 DRUG

N-803 (15 mcg/kg, subcutaneously) will be given on day 1 to patients enrolled in arm 3.

Also known as: Anktiva

Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1)

TriAd vaccine BIOLOGICAL

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

Also known as: ETBX-011, ETBX-051 & ETBX-061

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)

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 40156838 RESULT

• Redman 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.

  PMID: 35727629 DERIVED

• Saint 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.

  PMID: 33720067 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

bintrafusp alfa protein, human; ALT-803

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Results Point of Contact

• Title: Dr. Hoyoung Maeng
• Organization: National Cancer Institute

hoyoung.maeng@nih.gov

240-781-3253

Study Officials

• Hoyoung Maeng, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2020
• First Posted: January 30, 2020
• Study Start: June 9, 2020
• Primary Completion: August 24, 2021
• Study Completion: June 12, 2023
• Last Updated: July 16, 2025
• Results First Posted: August 8, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)