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.
Phase 1: Age greater than or equal to 1 year and less than or equal to18 years
Phase 2 Neuroblastoma (NBL) cohort: Age greater than or equal to 1 year and less than or equal to 30 years
Phase 2 Rhabdomyosarcoma (RMS) cohort: Age greater than or equal to 1 year and less than or equal to18 years
Phase 1: Refractory, progressive or relapsed non-central nervous system (CNS) solid tumors who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse
Prior treatment with PEEL-224.
Subjects receiving any other anti-cancer agents.
Subjects with primary central nervous system (CNS) solid tumors or central nervous system (CNS) metastatic disease.
Subjects with prior allogeneic stem cell or solid organ transplantation.
Sequential
PEEL-224
DrugPEEL-224 (PEG-\[SN22\]4) is a novel topoisomerase I inhibitor
Vincristine
DrugVincristine is an inhibitor of microtubular formation which is approved by the Food and Drug Administration (FDA) and is commercially available.
Temozolomide (TMZ)
DrugTemozolomide is an alkylating agent which is approved by the FDA and is commercially available.
Phase 1A and Phase 1B: Number of participants who experience a dose limiting toxicity (DLT)
The observation of a dose-limiting toxicity (DLT) or lack of observation of DLT in the period between treatment initiation up to initiation of cycle 2 treatment. A dose limiting toxicity (DLT) describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.
Phase 2 Neuroblastoma Cohort (NBL): Number of paricptants who achieve a complete response (CR), partial response (PR), or minor response (MR)
Objective response as assessed by the Revised International Neuroblastoma Response Criteria (INRC). Response is defined as complete response (CR), partial response (PR) or minor response (MR), using best response measured at any point prior to local control.
Phase 2 Rhabdomyosarcoma (RMS) Cohort: Number of participants who achieve a complete response (CR) or partial response (PR)
Objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Response is defined as complete response (CR) or partial response (PR), using best response measured at any point prior to local control.
Number of subjects with an Adverse Event (AE) of greater than or equal to grade 3 at least possibly attributable to study treatment
Adverse Events (AEs) will be graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Area under the plasma-concentration-time-curve of PEEL-224
To characterize the pharmacokinetic (PK) profile of free SN22 and SN22 bound to PEG (PEEL-224)
Number of participants demonstrating anti-tumor activity of PEEL-224
To preliminarily evaluate antitumor activity of PEEL-224 by estimating event-free survival (EFS)
Number of participants demonstrating anti-tumor activity of the combination of PEEL-224, vincristine and temozolomide
To preliminarily evaluate antitumor activity of the combination of PEEL-224, vincristine and temozolomide by estimating event-free survival (EFS )
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Theodore Laetsch
Lead sponsor
Children's Hospital of Philadelphia
Sponsor institution
Peel Therapeutics Inc
Collaborator
University of Pennsylvania
Collaborator
