Pembrolizumab With Axitinib in Recurrent Endometrial Cancer

Inclusion Criteria: * Subjects must have recurrent endometrial cancer with deficient mismatch repair system. Mismatch repair deficiency is defined by 1. Immunohistochemistry with loss of expression of one of these proteins in tumor tissue as defined by standard of care: MLH1, MSH2, MSH6 and PMS2, 2. Microstaellite (MSI) unstable by PCR per standard of care, 3. MSI high by next generation sequencing using commercial platform specifically CARIS, TEMPUS or Foundation testing. * Subjects must have histologically confirmed endometrioid, clear cell, high grade serous, undifferentiated carcinoma or mixed histology. * Must have had prior therapy with a PD1 inhibitor, pembrolizumab. * Up to 5 prior lines of therapy are allowed. * Prior anti-angiogenesis therapy is not allowed. Bevacizumab if given with chemotherapy in primary or adjuvant setting is allowed if treatment-free interval exceeded 6 months. * Subjects must have measurable disease based on RECIST 1.1 with at least one target lesion. * Subjects must have an ECOG performance status of 0-1. * Subjects must have normal organ and marrow function as defined below within 14 days of enrollment unless otherwise indicated: * Hemoglobin ≥ 9.0 g/dl (may have been transfused) * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN orAST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver). * Estimated Creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) * TSH within normal institutional limits. If elevated, patient can be eligible if evaluated by an endocrine specialist, placed on replacement therapy and deemed eligible with no current or prior autoimmune disease. * Subjects must have the ability to understand and the willingness to sign a written informed consent document. * Negative serum or urine pregnancy test at screening for women of childbearing potential. * Willing to use highly effective contraception throughout the study and for at least 30 days after last treatment administration if childbearing potential exists * Availability of an archival FFPE tumor tissue block from primary diagnosis specimen, metastatic, or recurrent site. If an FFPE tissue block cannot be provided then 15 unstained slides (10 minimum) will be acceptable. Please refer to the laboratory manual for complete details. * Urinary protein \<2+ by urine dipstick. If dipstick is \>2+, then 24-hour urinary protein \<2 g per 24 hours is required. * No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure (BP) readings taken at least 1 hour apart whether same visit or different visits. The baseline systolic BP readings must be \<140 mm Hg, and the baseline diastolic BP readings must be \<90 mm Hg. The use of antihypertensive medications to control BP is allowed. Exclusion Criteria: * Patients with sarcoma or carcinosarcoma * Mismatch repair proficient tumors * Patients with primary platinum refractory cancer defined as progressing during or within 3 months of completing primary platinum therapy. * Prior anti-cancer therapy within 3 weeks prior to study enrollment. * Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. * Patients having received prior therapy with PD1 or PDL1 or CTLA4 inhibitors or other immunotherapeutic agents except pembrolizumab. * Patients having received prior anti-VEGF therapy as explained above * Bowel obstruction (with or without gastrostomy tube) or inability to take oral medications * Patients with a prior or current bowel perforation or fistula * Uncontrolled hypertension defined as 140/90 or greater despite medical management with multiple medications * ECOG performance \>1 * Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. * Patients currently on immunosuppressive therapy except: * Intra-nasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) * Steroids as premedication for hypersensitivity reaction (e.g., CT scan premedication)." * Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent * Patients who are pregnant or breast feeding. * Known history of testing positive for HIV or known acquired immunodeficiency syndrome. * Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis. * Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Individuals with a history of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: breast cancer in situ, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. * Prior organ transplantation including allogenic stem-cell transplantation. * Active infection requiring intravenous systemic therapy. * Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) * Vaccination within 4 weeks of the first dose of treatment and while on trials is prohibited except for administration of inactivated vaccines. * Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5 Grade ≥ 3)" * Persistent toxicity related to prior therapy (NCI CTCAE v. 5 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable. * Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. * Gastrointestinal abnormalities including: * Inability to take oral medication; * Requirement for intravenous alimentation; * Treatment for active peptic ulcer disease in the past 6 months; * Active gastrointestinal bleeding, unrelated to cancer, as evidenced by clinically significant hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; * Malabsorption syndromes. * Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed. * Evidence of inadequate wound healing. * Grade \>3 hemorrhage within 4 weeks of patient enrollment. * Evidence of tumor involvement of the myocardium or pericardium or tumor thrombus extending to the heart. * Ongoing known cardiac dysrhythmias of NCI CTCAE Grade \>2 or prolongation of the QTc interval to \>500 msec. * Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4/5 inhibitors, including their administration within 10 days prior to patient enrollment (eg, grapefruit juice or grapefruit/grapefruit-related citrus fruits \[eg, Seville oranges, pomelos\], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed. * Current use or anticipated need for drugs that are known strong CYP3A4/5 inducers, including their administration within 10 days prior to patient enrollment, eg, phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, St John's wort.