Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer

NCT04906382 | Terminated Early Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20173NCI-2021-01367
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lynch Syndrome; Recurrent Endometrial Carcinoma; Recurrent Endometrial Clear Cell Adenocarcinoma; Recurrent Uterine Corpus Carcinosarcoma; Mismatch Repair Deficiency; Recurrent Endometrial Cancer; Metastatic Endometrial Cancer

Outcome Measures

Primary Outcomes (3)

• T-cell receptor (TCR) profiles

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

  Up to 24 months

• T-cell receptor (TCR) clonality

  Measurements of TCRB clonal expansion in peripheral blood.

  Up 24 month

• T-cell receptor (TCR) diversity

  Measurements of TCRB diversity in peripheral blood

  Up to 24 months

Secondary Outcomes (6)

• Tumor mutational profiles

  Up to 3 years

• PD-L1 expression and other immune markers in tissue

  up to 24 weeks

• Overall response rate (objective response rate complete response [CR] and partial response [PR]; clinical benefit rate CR + PR + stable)

  Up to 3 years

• Progression-free survival

  From date of enrollment to date of progressive disease, assessed up to 5 years

• Overall survival

  Up to 5 years

Study Arms (1)

Treatment (tislelizumab)

EXPERIMENTAL

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.

Procedure: Biopsy; Drug: Carboplatin; Drug: Paclitaxel; Biological: Tislelizumab

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (tislelizumab)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (tislelizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (tislelizumab)

Tislelizumab BIOLOGICAL

Given IV

Also known as: BGB-A317

Treatment (tislelizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
• Age \>= 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
• All patients with recurrent endometrial carcinoma, of any histology including clear cell, serous papillary carcinomas, and carcinosarcoma, whose disease is not amenable to definitive local therapy (including surgery and/or radiation therapy)
• Patients must have deficient mismatch repair as demonstrated by lack of expression of at least 1 mismatch repair protein by immunohistochemistry, or evidence of microsatellite instability (MSI) high, or evidence of Lynch syndrome
• The patient must have a lesion that is amenable to safe biopsy and the patient must agree to pre-and post-treatment biopsies
• Patients may have received radiation for the treatment of endometrial cancer
• Patient must have recovered from toxicity related to prior treatment to grade 2 or less
• At least two weeks should have elapsed since completion of prior chemotherapy or 5 half-lives (whichever is shorter), or 4 weeks from radiation involving the whole pelvis or over 50% of the spine
• At least 1 measurable lesion as defined per RECIST v1.1 that is amenable to biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (must not have required a blood transfusion or growth factor support =\< 14 days before sample collection at screening) (during screening or =\< 14 days prior to first dose of study drug)
• Platelets \>= 75 x 10\^9/L (must not have required a blood transfusion or growth factor support =\< 14 days before sample collection at screening) (during screening or =\< 14 days prior to first dose of study drug)
• Hemoglobin \>= 9.0 g/dL (must not have required a blood transfusion or growth factor support =\< 14 days before sample collection at screening) (during screening or =\< 14 days prior to first dose of study drug)
• Serum creatinine =\< 1.5 x ULN (upper limit of normal) or estimated glomerular filtration rate \>= 30 mL/min/1.73 m\^2 by Chronic Kidney Disease Epidemiology Collaboration equation (during screening or =\< 14 days prior to first dose of study drug)
• Serum total bilirubin =\< 1.5 x ULN (total bilirubin must be \< 3 x ULN for patients with Gilberts syndrome) (during screening or =\< 14 days prior to first dose of study drug)

You may not qualify if:

• Prior therapies targeting PD-1 or PD-L1
• Patients with symptomatic pleural effusion are excluded
• Active leptomeningeal disease or uncontrolled brain metastasis.
• Following treatment, these patients may then be eligible, provided all other criteria, including those for patients with a history of brain metastases, are met
• Active autoimmune diseases or history of autoimmune diseases that may relapse.
• Any active malignancy =\< 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
• Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication =\< 14 days before first dose of study drug
• With uncontrolled diabetes or laboratory test abnormalities \> grade 1 in potassium, sodium, or corrected calcium despite standard medical management or \>= grade 3 hypoalbuminemia =\< 14 days before first dose of study drug
• With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
• With severe chronic or active infections (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to randomization or first dose of study drugs
• Human immunodeficiency virus (HIV) testing is not required by protocol unless clinically indicated. Known HIV positive patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Any major surgical procedure requiring general anesthesia =\< 28 days before first dose of study drug
• Prior allogeneic stem cell transplantation or organ transplantation
• Any of the following cardiovascular risk factors:

Sponsors & Collaborators

• Floor Backes, MD: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms; Turcot syndrome

Interventions

Biopsy; Carboplatin; Paclitaxel; Taxes; tislelizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Floor Backes, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: May 28, 2021
• Study Start: July 1, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)