Atezolizumab and Bevacizumab in Treating Patients with Advanced, Recurrent, or Refractory Endometrial Cancer

Inclusion Criteria

• Histologic or cytologic diagnosis of endometrial carcinoma (including endometrioid, serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma)
• Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments
• At least 1 prior platinum-based chemotherapeutic regimen, but not more than 2 prior chemotherapeutic regimens, for management of endometrial carcinoma. Prior treatment may include chemotherapy, and/or consolidation/maintenance therapy
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be >= 10 mm in long axis when measured by CT, magnetic resonance imaging (MRI), or caliper measurement by clinical exam. Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• Female patients 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods as defined below: * Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final dose of atezolizumab and for bevacizumab after the final dose of bevacizumab. * A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. * Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. * Hormonal contraceptive methods must be supplemented by a barrier method. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• Absolute neutrophil count (ANC) >= 1500/uL (within 4 weeks before the first dose of study drug)
• Platelet count >= 100,000/uL (within 4 weeks before the first dose of study drug)
• Hemoglobin >= 9 g/dL (within 4 weeks before the first dose of study drug)
• Total bilirubin must be < 1.5 x the upper limit of normal (ULN) (within 4 weeks before the first dose of study drug)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be =< 3 x the upper limit of the normal range (within 4 weeks before the first dose of study drug). AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver
• Creatinine =< 1.5 x ULN or creatinine clearance >= 50 mL/min/1.73 m^2 based either on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection (within 4 weeks before the first dose of study drug) * Urine protein < 2.0. All patients with >= 2 + protein on dipstick urinalysis at baseline must undergo a urine protein-to-creatinine ratio and/or 24-hour urine collection and demonstrate < 1.0 of protein
• Urine protein: creatinine ratio (UPCR) =< 1.0 (For UPCR > 1, a 24-hour urine protein should be obtained and the level should be < 1000 mg) (within 4 weeks before the first dose of study drug)
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 4 weeks before the first dose of study drug) (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low molecular-weight heparin or warfarin, should be on a stable dose) (within 4 weeks before the first dose of study drug)
• Able to understand and willing to sign the informed consent form and the written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
• Must have ability to comply with the study protocol, in the investigator’s judgment
• Patients microsatellite instability (MSI) status must be known (via immunohistochemistry)
• Patients should have archival tumor tissue available or agree to have pre-treatment tumor biopsy if no archival tissue is available for correlative studies If unable to be safely biopsied and patient desires enrollment, may be enrolled per principal investigator discretion
• Life expectancy of greater than 12 weeks

Exclusion Criteria

• Positive serum pregnancy test during the screening period or a positive urine pregnancy test on day 1 before first dose of study drug. Women who are lactating and breast feeding are not eligible
• Previous treatment with anti−PD-1, or anti−PD-L1 therapeutic antibody
• History of auto-immune disorders (systemic lupus erythematosus [SLE], sarcoidosis, rheumatoid arthritis [RA], Crohn’s)
• Initiation of treatment with systemic corticosteroids (either IV or oral steroids, excluding inhalers) within 1 week before administration of the first dose of study drug
• Sensory or motor neuropathy >= grade 2
• Patients with symptomatic, untreated central nervous system (CNS) metastasis * Patients with a history of treated CNS lesions are eligible, provided that all of the following criteria are met: ** Measurable disease, per RECIST version (v)1.1, must be present outside the CNS ** The patient has no history of intracranial hemorrhage or spinal cord hemorrhage ** Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord) ** There is no evidence of interim progression between completion of CNS directed therapy and the screening brain scan ** The patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment ** The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted * Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan
• Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, severe cardiac disease, bleeding diathesis, active infection, or any other condition that could compromise participation of the patient in the study
• Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Patients who have had investigational therapy, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier; however, the following therapies are allowed: * Hormone-replacement therapy or oral contraceptives * Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1) * Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to cycle 1, day 1
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, compounds similar to bevacizumab or atezolizumab, or Chinese hamster ovary products
• Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
• History of abdominal/pelvic fistula, gastrointestinal perforation and/or intraabdominal abscess within 6 months prior to day 1. Serious or non-healing wound, active ulcer or bone fracture
• Immunocompromised patients and subjects known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy. NOTE: Subjects known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial