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

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. ...

Timeline

Start

2020-06-09

Primary completion

2021-08-24

Completion

2023-06-12

Publications

• Results 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.
• 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.
• 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.

Drugs

Indications