Pbi-shRNA™ EWS/FLI1 Type 1 LPX in Subjects With Advanced Ewing's Sarcoma

Summary

Participation Requirements

Description

Study testing of pbi-shRNA™ EWS/FLI1 Type 1 LPX will involve patients (?age 8) with advanced Ewing's sarcoma. The first 3 subjects enrolled onto the study as well as the first subject enrolled into each dose cohort must be 16 years of age or older. pbi-shRNA™ EWS/FLI1 Type 1 LPX will be given via in...

Study testing of pbi-shRNA™ EWS/FLI1 Type 1 LPX will involve patients (?age 8) with advanced Ewing's sarcoma. The first 3 subjects enrolled onto the study as well as the first subject enrolled into each dose cohort must be 16 years of age or older. pbi-shRNA™ EWS/FLI1 Type 1 LPX will be given via intravenous infusion. Patients will be accrued in 3- patient dose escalation cohorts using the following escalation schema (50%?33%?25%?25%?25%) at a starting IV dose of 0.04 mg/kg. If 1 of 3 subjects within a dose cohort experiences a Dose Limiting Toxicity (DLT), that dose cohort will be expanded to six subjects provided no further subjects experience a DLT. If no further subjects experience a DLT, dose-escalation may continue. If ?2 subjects within a dose cohort experiences a DLT, this will define the DLT dose level and the Maximum Tolerated Dose (MTD) will have been exceeded. The preceding dose level will be expanded to a total of 6 subjects and, if ?1 subject experiences a DLT, that dose level will be considered the maximum tolerated dose (MTD). If no further subjects experience a DLT, dose-escalation may resume per escalation schema. Once the presumptive MTD is reached, an additional 6 subjects will be treated at that dose, designated the expanded MTD dose cohort. Serum for pharmacokinetics (PK) analysis will be collected on Cycle 1, Week 1, Day 1 (C1W1D1), Cycle 1, Week 6, Day 4; and Cycle 2, Week 1, Day 1 at following time points (±10%):30 minutes prior to administration and at the following time points after initiation of study agent administration: 5 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours. Serum for cytokine analysis will be collected on Cycle 1, Week 1, Day 1 at following time points (±10%): 2 hours, 6 hours, and 24 hours. Serum for cytokine analysis will also be collected on Cycle 2, Week 1, Day 1 and Cycle 3, Week 1, Day 1, at following time points (±10%): 30 minutes prior to administration and at 6 hours after initiation of study agent administration. Blood for analysis of RNA mechanism will be collected prior to administration of the study agent and 48 hours after study agent administration (with a 10% window). Blood for RNA will be collected at the first and last dose of each cycle (e.g. C1W1D1, C1W6D4). Blood for circulating tumor DNA (ctDNA) analysis will be collected at Cycle 1 Week 1 Day 1, Cycle 1 Week 3 Day 1, Cycle 2 Week 1 Day 1 prior to product infusion and every even cycle thereafter at Week 1 Day 1 prior to product infusion. If available, a biopsy or pleural fluid will be collected 1 to 3 weeks prior to Cycle 1 Week 1 Day 1 and 72 hours after the last dose of Cycle 1.

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