This phase 2 study using atezolizumab and bevacizumab aims to study the objective tumor
response in women with recurrent endometrial cancer. Drugs will be administered via IV every
21 days until disease progression, unacceptable toxicity, or loss of clinical benefit as
determined by investigator. Subjects will receive routine cancer care as well as tests and
procedures required for the purposes of this study. It is expected this combination will be
produce an anti-cancer effect with manageable toxicities in this patient population.
Inclusion Criteria:
1. Histologic or cytologic diagnosis of endometrial carcinoma (including endometrioid,
serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma).
2. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has
relapsed or is refractory to curative therapy or established treatments.
3. 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.
4. Measurable disease by 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, MRI, or caliper measurement by clinical
exam. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
5. Female patients 18 years or older.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
7. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods as defined in study protocol.
8. Clinical laboratory values as specified in study protocol within 4 weeks before the
first dose of study drug.
9. 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standard medical care, with the understanding that consent may be withdrawn by the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.
10. Must have ability to comply with the study protocol, in the investigator's judgment.
11. Patients MSI status must be known (via immunohistochemistry)
12. 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.
13. Life expectancy of greater than 12 weeks.
Exclusion Criteria:
1. 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.
2. Previous treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody.
3. History of auto-immune disorders (SLE, sarcoidosis, RA, Crohn's).
4. 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
5. Sensory or motor neuropathy ≥ Grade 2.
6. Patients with symptomatic, untreated Central nervous system (CNS) metastasis; Patients
with a history of treated CNS lesions are eligible if all criteria provided per study
protocol are met.
7. 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.
8. 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.
9. Patients with prior allogeneic bone marrow transplantation or prior solid organ
transplantation
10. 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, some therapies are allowed per study
protocol.
11. 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
12. 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.
13. 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
14. 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
15. Immunocompromised patients and subjects known to be 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.
