If symptoms resolve quickly, resume infusion at 50% of original rate with close monitoring of any worsening signs and symptoms, otherwise dosing held until resolution of symptoms with mandated premedication for the next scheduled visit. If not improving, consider administration of glucocorticoids and stop the infusion for that day. If the participant has a second IRR Grade ≥ 2 on the slower infusion rate despite premedication, the infusion should be stopped, and the investigator may consider withdrawal of this participant from the study. Grade 3 or Grade 4 – severe or life-threatening oGrade 3: Prolonged (for example, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. oGrade 4: Life-threatening consequences; urgent intervention indicated.Stop the infusion of study intervention immediately and disconnect infusion tubing from the participant with additional appropriate medical measures and closely monitor until deemed medically stable by the attending Investigator. Hospitalization and/or close monitoring is recommended  Administration of glucocorticoids may be required For Grade 3 or 4 IRRs, permanent discontinuation of study intervention is mandated. 34 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 NCI-CTCAE Grade Treatment Modification Once the infusion is interrupted or rate reduced to 50% of previous infusion rate, it must remain decreased for all subsequent infusions. For all types and grades of infusion reactions, details about drug physical constitution, method of preparation, and infusion must be recorded. Participants should be instructed to report any delayed reaction immediately. Once the infusion is interrupted or rate reduced to 50% of previous infusion rate, it must remain decreased for all subsequent infusions. For all types and grades of infusion reactions, details about drug physical constitution, method of preparation, and infusion must be recorded. Participants should be instructed to report any delayed reaction immediately. Table 3 Immune-related adverse events (irAEs) Immune-related AEs are specific to immunotherapies and vary by organ system. Following immune-related AEs are important identified risks for M7824: Immune-related pneumonitis Immune-related hepatitis Immune-related colitis Immune-related nephritis and renal dysfunction Immune-related endocrinopathies (thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus, pituitary disorders) Immune related rash Other immune-related events (myositis, myocarditis, encephalitis) Following immune-related AEs are important potential risks for M7824: Guillain-Barré syndrome Uveitis Pancreatitis Myasthenia gravis/myasthenic syndrome Recommended guidance and management for specific irAEs are provided in the current NCCN (guideline available at http://www.nccn.org). Requirements in addition to NCCN guidelines: Permanent treatment discontinuation is required in case of immune-related Grade 4 rash/inflammatory dermatitis, nephritis, autoimmune hemolytic anemia, hemolytic uremic syndrome, aplastic anemia, immune thrombocytopenia, acquired thrombotic 35 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 thrombocytopenic purpura inflammatory arthritis, myositis and polymyalgia-like syndrome. For Grade 4 immune-related lymphopenia, permanent treatment discontinuation will be required, if lymphopenia is considered immune-related in nature, no clear alternative explanation exists for the event, and it does not resolve within 14 days. Permanent treatment discontinuation is not required when the AE is manifested by a single laboratory value out of normal range without any clinical correlates. In this case, treatment should be held until the etiology is determined. If the event is not considered immune-related and resolves to Grade ≤ 1, restarting treatment may be considered. For Grade 1 immune-related pneumonitis: continue treatment. If clinically indicated, monitor participants weekly or more frequently as needed with history, physical examination and pulse oximetry. If symptoms appear and/or changes in the physical exam are noted, treat as Grade 2. For myositis: in case of management with rituximab, treatment should be discontinued. For Grade 3 or 4 endocrinopathies: withhold until clinically stable or permanently discontinue depending on severity. For hepatitis with no tumor involvement of the liver: withhold if total bilirubin increases to more than 1.5 and up to 3 times ULN, permanently discontinue if more than 3 times ULN. Hepatitis with tumor involvement of the liver: permanently discontinue if total bilirubin increases to more than 3 times ULN. Table 4 Management of M7824 mediated Skin Reactions Skin reactions are considered important identified risk for M7824. Hyperkeratosis Keratoacanthoma Cutaneous squamous cell carcinoma (cSCC) Basal cell carcinoma Actinic keratosis Management Discontinuation or termination not required in most cases. Continuation of treatment should be evaluated by the Investigator. Emollients may be used Develop diagnostic and treatment plan in collaboration with Investigator and dermatologist Treatment follow-up will depend on number and localization of lesions. oSingle lesion: full excision may be recommended 36 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 oMultiple lesion or location not suitable for full excision: Mohrs surgery, cryotherapy or other standard treatment options depending on pathology. Retinoids may be used after discussion with Investigator. Close clinical follow-up for re-evaluation, resolution and potential recurrence should be implemented In general, treatment of skin lesions should be based on local guidelines/standard of care. Additional consideration: Keratoacanthoma lesions may resolve spontaneously without surgical intervention within weeks after discontinuing M7824. Consult with Medical Monitor as needed for management of skin lesions. Table 5 Management of Anemia Anemia is considered an important identified risk for M7824. All relevant hematological testing for treatment-related anemias should be done prior to a blood transfusion, if clinically feasible Basic Anemia Evaluation CBC with emphasis on red cell indices If indicated and at clinical discretion, the following should be considered: oIron studies oSerum Folate and Vit B12 values oCoagulation factors oFecal occult blood oUrinalysis oHormone panel: TSH, Erythropoietin oPeripheral blood smear Further Recommendation Based on Suspected Etiology (in Addition to Basic Anemia Testing) Suspected Hemolysis obilirubin, LDH, Coombs test, haptoglobin Suspected bleeding: oConsider imaging/interventional radiology consultation as indicated oConsider imaging and/or endoscopy as clinically indicated Suspected aplastic anemia: oHematology consultation oConsider bone marrow aspiration/morphologic evaluation 37 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 Additional consideration: In general, blood transfusions and erythroid growth factors are permitted as clinically indicated. Table 6 Management of Bleeding Adverse Events Bleeding Adverse Events Bleeding adverse events are considered important identified risk for M7824.