lymphangitic spread of disease (disease progression). As of August 2017, > 500 participants have been treated with M7824 across multiple solid tumor expansion cohorts. The safety profile is consistent with other monotherapy checkpoint inhibitors, with the exception of keratoacanthomas and cutaneous squamous cell carcinomas which have occurred in approximately 3-5% of participants and are well managed with surgical excision. 87 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 These lesions have not been a criterion for treatment discontinuation, but thus far have all spontaneously regressed following treatment discontinuation. In addition, after discussion among NCI investigators on multiple protocols using M7824 bleeding events ranging from low grade gingival bleeding and epistaxis to more serious hemoptysis, GI bleeding and hematuria have been observed. Some of these events can be attributed to bleeding events related to cancer directly. However, there remains the possibility that M7824 may increase the overall risk of bleeding in ways that may not be directly related to direct tumor bleeding. It is hypothesized that this possible increased bleeding risk may be due to TGF beta inhibition which has an effect on angiogenesis. Accordingly, participants will be notified of the same possible risk in the informed consent document for this study (e.g., gum bleeding, nose bleeds, coughing up blood, blood in their urine, or blood in the stool). Potential risks include anemia, alterations in wound, healing or repair of tissue damage, and embryofetal toxicity. In addition, at least 2 instances of nodular regenerative hyperplasia have been observed with the use of this agent. 14.2.3 Formulation and Preparation M7824 is provided as a sterile liquid formulation and packaged at a 10 mg/mL concentration in USP/ Ph Eur type I 50R vials that are filled with drug product solution to allow an extractable volume of 60 mL (600 mg/60 mL). The vials are closed with rubber stoppers in serum format complying with USP and Ph Eur with an aluminum crimp seal closure. Each single-use vial contains 600mg of M7824, formulated as 10mg/mL of active, 6% (w/v) Trehalose, 40 mM NaCl, 5 mM Methionine, 0.05% (w/v) Tween 20, 10 mM LHistidine at pH 5.5. The liquid formulation is diluted directly with 0.9% sodium chloride solution for injection. The estimated volumes of delivery are anticipated to be no more than 250mL. The verified concentration range in the infusion solution is 0.16 mg/mL to 9.6 mg/mL. 14.2.4 Stability and Storage M7824 must be stored at 2℃ to 8℃ until use. Product stored at room temperature for extended periods of time might be subject to degradation. M7824 must not be frozen. Rough shaking of the reconstituted solution must be avoided. The chemical and physical in-use stability for the infusion solution of M7824 in 0.9% sodium chloride for injection has been demonstrated for a total of 72 hours at room temperature; however, from a microbiological point of view, the diluted solution should be used immediately and is not intended to be stored unless dilution has taken place in controlled and validated aseptic conditions. 88 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 No other drugs should be added to the infusion containers containing M7824. See Manual of Preparation of approved ancillary supplies.