Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Syndrome

Recurrence

Carcinosarcoma

Mixed Tumor, Mullerian

Adenocarcinoma, Clear Cell

Endometrial Neoplasms

Colorectal Neoplasms

Colorectal Neoplasms, Hereditary Nonpolyposis

Adenoma, Pleomorphic

Disease Attributes

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplastic Syndromes, Hereditary

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Turcot Syndrome

Malignant Mixed Mullerian Tumor

Uterine Carcinosarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Tislelizumab

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Chemo naïve patients receive tislelizumab 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.

Patients who have received prior chemotherapy will receive single agent tislelizumab 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.

Biopsy

Floor Backes, MD

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.

Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer

Pilot Study of Tislelizumab (BGB-A317) in Recurrent Mismatch Repair Deficient Endometrial Cancer and the Effect on the Tumor Microenvironment

1) Measurements of TCRB clonal expansion in peripheral blood. Measurements of TCR in peripheral blood/-tissue

Measurements of TCRB clonal expansion in peripheral blood.

Measurements of TCRB diversity in peripheral blood

Evaluated by Response Evaluation Criteria in Solid Tumors version 1.1.

Floor Backes

Principal Investigator

Spots Global Cancer Trial Database for recurrent uterine corpus carcinosarcoma