Pembrolizumab, Lenvatinib and IL-15 Superagonist N-803 in Combination With HER2 Targeting Autologous Dendritic Cell (AdHER2DC) Vaccine in Participants With Advanced or Metastatic Endometrial Cancer

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• Administration of any standard of care or investigational checkpoint inhibitors (e.g., anti-CTLA, anti-PD-1, anti-PD-L1, anti-TIGIT, anti-TIM3, or anti-LAG3 antibodies or small molecules) within 6 months prior to apheresis
• Surgery to abdomen/pelvis/chest within 3 months prior to apheresis
• Other malignancies diagnosed within 24 months prior to apheresis. NOTE: Participants who completed treatment for in-situ carcinomas (e.g., breast, cervix, bladder), or basal or squamous cell carcinoma of the skin are eligible if no ongoing treatment is needed per Standard of Care
• Arterial or venous thromboembolism within 6 months prior to apheresis
• History of cerebrovascular accident or stroke (transient ischemic attack, hemorrhagic or ischemic) within 6 months prior to apheresis
• History of hemoptysis or tumor bleeding within 1 month prior to apheresis
• Systemic corticosteroid therapy of higher than a physiologic dose (the equivalent of prednisone 10 mg/day) within 14 days prior to apheresis. NOTE: Any topical steroid medications (e.g., corticosteroid creams, ointments, and eye drops) are allowed
• Solid organ or allogeneic hematopoietic stem cell transplant recipients
• History of grade 3 or 4 immune related adverse events from the use of immune checkpoint inhibitors
• History of Lenvatinib use
• History of severe immediate hypersensitivity reaction to compounds similar to study drugs or their components (e.g., monoclonal antibody preparations)
• Functional or objective cardiac dysfunction: New York Heart Association (NYHA) Functional Capacity III or IV or Objective Assessment C or D
• History of gastrointestinal or non-gastrointestinal fistula >= Grade 3 (CTCAE v.5.0)
• Current gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
• Participants with active autoimmune disease or a history of autoimmune disease, which require immune suppressive treatment such as systemic corticosteroids or other systemic immune suppressants (e.g., methotrexate, cyclosporine, and biologics). NOTE: Participants with vitiligo, endocrine deficiencies on replacement dose are eligible
• Human immunodeficiency virus (HIV)-positive participants
• Uncontrolled intercurrent illness or situation that would limit compliance with study requirements
• Fridericia's corrected QT interval (QTcF) >= 480 msec or evidence of third-degree AV block on screening electrocardiogram (ECG)
• Ejection fraction by screening echocardiogram < 50 percent
• Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in IOCBP at screening)
• Participants requiring therapeutic anticoagulation regimen(s) (e.g., warfarin, rivaroxaban, apixaban, dabigatran, edoxaban, low molecular weight heparin [e.g., enoxaparin, dalteparin, tinzaparin], heparin, fondaparinux)
• Radiographic evidence of major blood vessel invasion/infiltration
• Any form of primary immunodeficiency

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• INCLUSION CRITERIA:
• Histologically confirmed endometrial cancer
• Radiographically confirmed metastatic or locally advanced disease
• Evaluable (measurable or non-measurable) disease, per RECIST 1.1
• HER2 IHC 1+, 2+ or 3+ tumor confirmed by PATHWAY HER2 (4B5) test. NOTE: The HER2 status in participants who had prior anti-HER2 therapy should be confirmed in the tumor tissue obtained after completing the anti-HER2 therapy
• Participants must have received and progressed after at least one (1) line of systemic therapy for endometrial cancer
• Age >=18 years
• ECOG performance status <=2
• Participants must have available tumor tissue or be willing to undergo a mandatory research biopsy. NOTE: Samples must be collected after HER2 directed therapy if the participant had anti-HER2 therapy
• Participants must have adequate organ and marrow function as defined below:; Absolute neutrophil count (ANC) > 1,000/microliter; Platelets > 100,000/microliter; Hemoglobin (Hgb) > 9 g/dL (any number of transfusions within 60 days before apheresis is allowed); Total bilirubin <=1.5 X upper limit of normal (ULN). NOTE: In participants with Gilbert s Syndrome or known liver metastasis, total bilirubin <=3.0 X ULN is allowed; Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) <=3.0 X ULN. NOTE: AST/ALT <=5.0 X ULN is allowed in participants with known liver metastasis; An estimated creatinine clearance (CrCl) <=1.5 X ULN OR >30 mL/min/1.73 m2 for participants with creatinine levels >1.5 X ULN (calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl); Dip stick urine protein < 3 or urine protein < 1 gram (g)/24 hour if dip stick urine is >= 3+
• Hepatitis B virus (HBV)-infected participants can be enrolled if HBV DNA is undetectable. Hepatitis C virus (HCV)-infected participants can be enrolled if HCV RNA level is undetectable
• Participants with previously treated non-active brain metastases or central nervous system metastases more than 28 days from definitive radiotherapy or surgery are eligible
• Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device (IUD), tube ligation, a partner has had the previous vasectomy, abstinence) at the time of study entry, for the duration of study treatment, and up to 6 months after the last dose of the study drug(s)
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s)
• Participants must be able to understand and be willing to sign a written informed consent document