Phase 2 N=21 Treatment

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

Head and Neck Cancer · Head and Neck Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT04247282 ↗

Enrolled (actual)

Serious AEs

15.0%

Results posted

Aug 2023

Primary outcome: Primary: Number of Participants Who Experience a Pathologic Complete Response (pCR) — 0; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: M7824 (Drug); N803 (Drug); TriAd vaccine (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Aug 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants Who Experience a Pathologic Complete Response (pCR)	0; 0	—
PRIMARY Number of Participants Who Experience Clinical to Pathologic Downstaging Upon Analysis of Resected Tumor After Completing Study Treatments	6; 2	—
SECONDARY 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	0; 0	—
SECONDARY Number of Participants That Experienced Grade 3 or 4 Immune Related Adverse Events (irAEs)	1; 0; 0; 1	—
SECONDARY Probability of Being Alive and Recurrence Free	84.6; 83.3; 84.6; 83.3	—
SECONDARY Percentage of Participants Who Are Alive	92.3; 83.3; 84.6; 83.3	—
SECONDARY Number of Participants With Treatment-related Adverse Events Causing a Delay of 4 Weeks or More Beyond Planned Surgery	0; 0	—

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. ...

Eligibility Criteria

INCLUSION CRITERIA:
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.

EXCLUSION CRITERIA

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., 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.
Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin). Patients enrolling on the M

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Data sourced from ClinicalTrials.gov (NCT04247282). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.