Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib and Avelumab/Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer

Running, not enrolling · Phase 2

Conditions studied: Metastatic Endometrial Cancer

In brief

This research study is evaluating a drug called Avelumab alone and in combination with Talazoparib or Axitinib as a possible treatment for recurrent or metastatic endometrial cancer.

Key facts

Study ID: NCT02912572
Run by: Dana-Farber Cancer Institute
People needed: 106
Starts: 2016-11-14
Expected to finish: 2026-11-01
Last updated by the study team: 2026-07-28

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

Participants must be classified into one of the following cohorts of recurrent or persistent endometrial cancer of any histology:
The MSI/POLE cohort includes endometrial cancers that are:
-MSI-H as determined by immunohistochemical complete loss of expression (absence of nuclear immunoreactivity) of at least one of the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. This test is now done routinely for every newly diagnosed endometrial cancer patient in most centers in the US.
And/OR:
-POLE-mutated, i.e. endometrial cancers known to harbor mutations in the exonuclease domain (amino acid residues 268-471) of polymerase e (POLE) as determined by targeted sequencing or other next generation sequencing assay. Any Clinical Laboratory Improvement Amendments (CLIA)-approved genomic test documenting mutations in the exonuclease domain of POLE gene (amino acid residues 268-471) in the tumor will be accepted as proof of presence of POLE mutations and will lead to classification into this patient cohort.
The MSS cohorts include:
Endometrial cancers that are MSS as determined by normal immunohistochemical nuclear expression of all the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. Tumors which have not been sequenced for POLE mutations (i.e. their POLE mutations status is unknown) but are MSS, will be included in this cohort.
All patients must have measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.
Prior Therapy:
There is no upper limit of prior therapies but patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Any platinum based chemotherapy (single agent platinum or any platinum doublet) administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. Furthermore, patients who have only received chemotherapy in the adjuvant setting will be eligible for the study.
Prior hormonal therapy is allowed.
Patients must NOT have received any class of drugs targeted to the PD-1/PD-L1 pathway.
Patients must NOT have received any prior PARP inhibitor therapy (for patients being considered for the avelumab/talazoparib cohort only).
Patients must NOT have received prior axitinib (for patients being considered for the avelumab/axitinib cohort only).
Age of 18 or greater years. Because insufficient dosing or adverse event data are currently available on the use of Avelumab, talazoparib, and/or axitinib in participants < 18 years of age, children are excluded from the study. Endometrial cancer is very rare in the pediatric population.
ECOG performance status 0 or 1 (reference Appendix A for ECOG performance status criteria).
Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue OR 15 unstained 5-micron slides from the original surgery or biopsy or from a biopsy of recurrent disease.
Participants must have normal organ and marrow function as defined below:
absolute neutrophil count >1,500/mcL
platelets >100,000/mcL
hemoglobin ≥ 9g/dL
total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
creatinine within normal institutional limits OR
creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.

You may not qualify if…

Participants who have had 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 due to agents administered more than 4 weeks earlier.
Participants who are receiving any other investigational agents.
Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
History of allergic reactions attributed to avelumab or any component in its formulations, or compounds of similar chemical or biologic composition to avelumab. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
Participants with a history of treatment with an anti-PD-1, anti-PD-L1, anti-CTLA-4 or other investigational agents that target immune checkpoint inhibitors.
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness, which may compromise the efficacy of immunostimulatory therapy.
Positive test for HBV surface antigen
Positive Hepatitis C antibody and positive confirmatory HCV RNA test. The confirmatory HCV RNA test is not required if the HCV antibody is negative. If Hepatitis C antibody is positive, the confirmatory HCV RNA test should be done and if it is negative, then participants are eligible.
Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
Active infection requiring systemic therapy.
Current or prior use of immunosuppressive medication within 7 days prior to enrollment with the following exceptions to this exclusion criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
Prior organ transplantation including allogeneic stem-cell transplantation.
Severe gastrointestinal conditions such as clinical or radiological evidence of bowel obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of inflammatory bowel disease.
Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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.
Known alcohol or drug abuse.
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 5 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.
All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment.
Any psychiatric condition that would prohibit the understanding or rendering of informed consent
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines.
Patients may not use natural herbal products or other "folk remedies" while participating in this study. Herbal medications include, but are not limited to St. John's Wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng.

Where it is running

University of Chicago — Chicago, Illinois, United States
Massachusetts General Hospital — Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
Dana Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.