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

Overview

This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy for patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy. Conventional therapy may include chemotherapy, surgery, radiation, autologous stem cell transplant, or targeted therapy.

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 \<70 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: Arm A Age ≥18 years and \<70 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.