Multi Tumor-Associated Antigen-Specific T Lymphocytes to Treat Patients With High Risk Solid Tumors

Description

In this dose escalation trial, three dose levels, with two arms dependent on age, will be tested for safety. Arm A will enroll patients age ≥18 years and <60 years and Arm B will enroll patients age ≥6 years and <18 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.

Description of Study Intervention:

The treatment schedule is as follows: Patients will receive an infusion of partially HLA-matched TAA-T any time >1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy >2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels:

BSA <1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells

There will be separate study arms for adult (Arm A) and pediatric (Arm B) patients:

Age Arm A Age ≥18 years and <60 years Arm B Age ≥6 years and <18 years

Enrollment will first be restricted to Arm A on dose level 1 (DL1). Following demonstration of safety, enrollment will start on dose level 2 (DL2) on Arm A for an additional 3 patients and we will contact the U.S Food and Drug Administration (FDA) with the safety data from the first 3 adults treated on DL1 to initiate enrollment on Arm B. Following demonstration of safety on Arm A at DL2, we will open enrollment to all patients (Arm A and B). Three patients will be enrolled at each dose level until the maximum tolerated dose (MTD) is determined, at which point to ensure safety, a total of 6 patients will be treated at the MTD.

One additional dose of TAA-Ts can be administered without lymphodepleting chemotherapy from day 45 after the initial infusion if there is a partial response (based on response evaluation criteria in solid tumors (RECIST)) or no response with stable disease, or if the patient receives immunosuppressive therapy that would compromise TAA-T persistence after the first infusion (such as corticosteroids), and if the patient has not experienced dose-limiting toxicities related to the study product and meets eligibility criteria for the additional infusion. Each patient will receive at least one TAA-T infusion and may receive a maximum of 2 doses. The first and second doses will be administered a minimum of 45 days apart. The expected volume of each infusion is 1 to 10 cc, though may be greater in larger patients. Dose escalation will occur once at least 3 patients on each study arm have completed the 45 day follow up period following their first TAA-T infusion. Response will be monitored after the first infusion at day 45, then at day 28 after subsequent infusion if administered.

Details