M7824 in Subjects With HPV Associated Malignancies

• INCLUSION CRITIERIA:
• Age greater than or equal to 18 years.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Subjects with cytologically or histologically confirmed locally advanced or metastatic human papillomavirus (HPV) associated malignancies including:
• Non-Neuroendocrine Cervical cancers
• P16 positive (P16+) Oropharyngeal cancers
• Anal cancers
• Vulvar, vaginal, penile, squamous cell rectal and neuroendocrine cervical cancers
• Other locally advanced or metastatic solid tumors (e.g. lung, esophagus) that are known HPV+
• Patients must have disease that is not amenable to potentially curative resection
• Subjects must have measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
• Adequate hematologic function at screening, as follows:
• Absolute neutrophil count (ANC) greater than or equal to 1 x 109/L
• Hemoglobin greater than or equal to 9 g/dL
• Platelets greater than or equal to 75,000/microliter.
• Adequate renal and hepatic function at screening, as follows:
• Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) greater than or equal to 40 mL/min per institutional standard
• Bilirubin less than or equal to 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN, unless liver metastases are present, then values must be less than or equal to 3 x ULN)
• The effects of M7824 on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and up to 60 days after the last dose of the drug. 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.
• Patients serologically positive for human immunodeficiency virus (HIV), Hep B, Hep C are eligible as long as the viral loads are undetectable by quantitative polymerase chain reaction (PCR). HIV positive patients must have cluster of differentiation 4 (CD4) count greater than or equal to 300 cells per cubic millimeter at enrollment, be on stable antiretroviral therapy and have no reported opportunistic infections within 12 months prior to enrollment.
• EXCLUSION CRITERIA:
• Pregnant women are excluded from this study because this drug has not been tested in pregnant women and there is 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.

• Patients with prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to the first drug administration except if the investigator has assessed that all residual treatment-related toxicities have resolved or are minimal and feel the patient is otherwise suitable for enrollment. Patients may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast).
• Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).
• Known intolerance to or life-threatening side effects resulting from prior checkpoint inhibitor therapy.
• Known active brain or central nervous system metastasis (less than 1 month out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment ( 14 days). In addition, the use of corticosteroids as premedication for contrast enhanced studies is allowed prior to enrollment and on study.
• Su