This clinical trial evaluates the effect of tislelizumab in treating patients with mismatch repair deficient endometrial cancer that has come back (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing DNA errors and damage. Mismatch repair deficient tumors (dMMR) may have difficulty repairing DNA mutations during replication that may affect tumor's response to therapy. Immunotherapy with monoclonal antibodies, such as tislelizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tislelizumab may help treat patients with mismatch repair deficient endometrial cancer.
PRIMARY OBJECTIVE: I. To evaluate the effect of tislelizumab (BGB-A317) on the diversity and dynamics of the T cell receptor repertoire in responders versus non-responders. SECONDARY OBJECTIVES: I. To evaluate the effect of tislelizumab on tumor mutational profiles between responders and non-responders. II. To evaluate the effect of tislelizumab +/- carboplatin/paclitaxel on PD-1/PD-L1 expression and other immune markers in tumor biopsies between responders and non-responders. III. To evaluate the safety and tolerability of tislelizumab +/- carboplatin/paclitaxel in patients with MMR deficient recurrent endometrial cancer. EXPLORATORY OBJECTIVES: I. To explore the effect of adding carboplatin/paclitaxel to tislelizumab on tumor mutational profiles. II. To explore the effect of adding carboplatin/paclitaxel to tislelizumab (BGB-A317) on the diversity and dynamics of the T cell receptor repertoire. III. To explore the objective antitumor activity (complete and partial response) of tislelizumab as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. IV. To explore the objective antitumor activity (complete and partial response) of tislelizumab/carboplatin/paclitaxel after single agent tislelizumab as measured by RECIST v1.1 criteria V. To explore the progression free survival in patients with mismatch repair deficiency (dMMR) recurrent endometrial cancer treated with tislelizumab +/- carboplatin/paclitaxel. OUTLINE: Patients receive tislelizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients who are chemotherapy naive with progressive disease, stable disease, or partial response, also receive carboplatin IV and paclitaxel IV every 21 days per standard of care for 6-9 cycles at the discretion of the treating physician. After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then periodically thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Undergo biopsy
Given IV
Given IV
Given IV
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
T-cell receptor (TCR) profiles
1\) Measurements of TCRB clonal expansion in peripheral blood. Measurements of TCR in peripheral blood/-tissue
Time frame: Up to 24 months
T-cell receptor (TCR) clonality
Measurements of TCRB clonal expansion in peripheral blood.
Time frame: Up 24 month
T-cell receptor (TCR) diversity
Measurements of TCRB diversity in peripheral blood
Time frame: Up to 24 months
Tumor mutational profiles
Evaluated using whole exome sequencing
Time frame: Up to 3 years
PD-L1 expression and other immune markers in tissue
Evaluated using immunohistochemistry
Time frame: up to 24 weeks
Overall response rate (objective response rate complete response [CR] and partial response [PR]; clinical benefit rate CR + PR + stable)
Evaluated by Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: Up to 3 years
Progression-free survival
Estimated using Kaplan-Meier method.
Time frame: From date of enrollment to date of progressive disease, assessed up to 5 years
Overall survival
Estimated using Kaplan-Meier method.
Time frame: Up to 5 years
Incidence of adverse events
Assessed using CTCAE v5.0
Time frame: Up to 2 years
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