This phase II trial studies how well autologous tumor infiltrating lymphocytes (LN-145) and pembrolizumab work in treating patients with transitional cell cancer that cannot be removed by surgery or has spread to other places in the body and have failed cisplatin-based chemotherapy. LN-145 is made up of specialized immune cells called lymphocytes or T cells that are taken from a patient's tumor, grown in a manufacturing facility and infused back into the preconditioned patient to attack the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving LN-145 may help control transitional cell bladder cancer when given together with pembrolizumab
PRIMARY OBJECTIVES: I. To evaluate the efficacy of autologous tumor infiltrating lymphocytes LN-145 (LN-145) in combination with pembrolizumab in subjects with advanced transitional cell bladder cancer (TCC) using the objective response rate (ORR) and the duration of response (DoR), using the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST version \[v\] 1.1). SECONDARY OBJECTIVES: I. To evaluate the efficacy of LN-145 in combination with pembrolizumab in subjects with TCC based on the progression-free survival (PFS) and overall survival (OS). II. To evaluate the safety of LN-145 in combination with pembrolizumab in subjects with TCC based on the adverse event (AE) profile per Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Roswell Park Cancer Institute
Buffalo, New York, United States
Objective response rate
The proportion of subjects who achieve either a confirmed partial response (PR) or complete response (CR) as best response as assessed per Response Evaluation Criteria in Solid Tumors 1.1. Will be evaluated per each disease assessment and calculated with the corresponding 95% two-sided confidence interval
Time frame: Up to 3 years
Incidence of adverse events (AEs)
Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 by grade of severity and relationship to the study treatment.
Time frame: From the first dose of cyclophosphamide up to 30 days from the last dose of IL-
Duration of response
Will be assessed by Kaplan-Meier methods
Time frame: Up to 3 years
Disease Control Rate
Derived as the sum of the number of subjects who achieved confirmed PR/CR or sustained stable disease (at least 6 weeks) divided by the number of subjects in the all-treated population x 100%. Will be assessed by Kaplan-Meier methods
Time frame: Up to 3 years
Progression-free survival
Will be assessed by Kaplan-Meier methods
Time frame: Up to 3 years
Overall Survival
From time of lymphodepletion to death due to any cause
Time frame: Up to 3 years
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