PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors

The phase 1 primary objective is to determine the pediatric recommended phase 2 dose (RP2D) of PEEL-224 as a single agent (phase 1A) and in combination with vincristine and temozolomide (phase 1B). The phase 2 primary objective is to estimate the objective response rate (ORR) in children with refractory, progressive and relapsed NBL and rhabdomyosarcoma (RMS) treated with the RP2D of PEEL-224 in combination with vincristine and temozolomide.

PEEL-224 will be a multi-institutional study conducted at pediatric cancer centers. Phase 1 will enroll approximately 24 subjects (maximum of 12 evaluable subjects in phase 1A and 12 evaluable subjects in phase 1B) between ages 1 to 18 years of age with a refractory, progressive or relapsed solid tumor. Phase 2 will enroll a maximum of 18 evaluable subjects with refractory, progressive or relapsed NBL and a maximum of 17 evaluable subjects with refractory, progressive or relapsed RMS. PEEL-224 will be administered at the assigned dose on days 1 and 8 of 21-day cycles as a single agent (phase 1A) or in combination with vincristine on days 1 and 8 and temozolomide on days 1-5 (phase 1B and phase 2). Subjects may continue protocol therapy for up to 24 cycles (approximately 18 months) in the absence of progressive disease or unacceptable toxicity. Subjects will be monitored with physical exams and labs on days 1 and 8 of each cycle and disease response assessments and patient reported outcome assessments will be performed after cycles 2, 4, 6, 9, 12, 18, and 24. During phase 1, PK blood samples will be drawn during cycle 1. The primary phase 1 endpoints are cycle 1 dose limiting toxicity (DLT) to define the RP2D. The primary phase 2 endpoint is best overall objective response to define the ORR.