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Trials in Progress and Late Breaking Clinical Trials

(P 427) PHASE 1/2 TRIAL TO EVALUATE THE SAFETY AND EFFICACY OF PEEL-224 IN COMBINATION WITH VINCRISTINE AND TEMOZOLOMIDE IN ADOLESCENTS AND YOUNG ADULTS WITH RELAPSED OR REFRACTORY SARCOMAS

Objective: Adolescents and young adults with sarcomas, such as Ewing sarcoma (EWS), desmoplastic small round cell tumor (DSRCT), rhabdomyosarcoma (RMS) and osteosarcoma (OS), experience substantial morbidity and mortality. While topoisomerase 1 (TOP1) inhibitors have activity across these malignancies, they have multiple limitations. PEEL-224 represents a novel tetravalent, pegylated, pro-drug formulation of SN22, an advanced TOP1 inhibitor with enhanced pharmacological properties. PEEL-224 is water-soluble, does not require hepatic activation, and has a prolonged half-life, allowing for increased drug delivery to tumor and once weekly dosing. SN22 does not undergo glucuronidation and ABC transporter-mediated cellular export, thereby reducing acquired resistance. The lack of glucuronidation and anticholinergic activity reduces GI toxicity. Pre-clinical data in EWS, DSRCT and RMS demonstrate significantly improved efficacy over irinotecan.

Methods: This is a prospective, open-label, single-arm, non-randomized, phase 1/2 clinical trial conducted at Dana-Farber Cancer Institute and three external sites (NCT06709495). Patients 12-49 with relapsed or refractory sarcomas receive PEEL-224 (days 1,8) in 21-day cycles in combination with vincristine (days 1,8) and oral temozolomide [days 1-5; V(P)T]. The phase 1 portion of the trial is designed to determine the recommended phase 2 dose of PEEL-224 given in combination with vincristine and temozolomide. During phase 2, there are two dedicated cohorts for patients with relapsed or refractory EWS and DSRCT designed to determine the objective response rate to V(P)T. Patients will be required to have measurable disease in both cohorts. There is a cohort for patients with “other” sarcomas designed to determine progression-free survival in patients with evaluable or measurable disease treated with V(P)T. Correlative biology includes pharmacokinetics, and tissue and ctDNA sequencing. The trial is now open and enrolling.

Results: N/A

Conclusion: N/A