Abstract LB266: A multicenter phase 1-2a clinical study of Orotecan® (oral irinotecan HCl, VAL-413) in patients with recurrent pediatric solid tumors
Authors: Jeffrey Bacha, Dennis Brown, James Geller, Javier Oesterheld, Patrick Thompson, Aerang Kim, Meghann McManus, Sarath Kanekal, Markos Leggas, Lorena Lopez, Neil Sankar, Noymi Yam, Lars Wagner
Journal: Cancer Research (2025)

Abstract Background: Intravenous irinotecan hydrochloride (IRN-IV) is approved for the treatment of adult colorectal cancer. An off-label regimen of IRN-IV administered as a 60-min i.v. infusion daily for 5-10 days, bi-weekly in combination with other agents such as temozolomide has been recommended for use in treating children with solid tumors (Blaney. ClinCanRes, 2001; Slotkin. PedBloodCan, 2023). While this regimen has shown promise in published clinical trials across a range of pediatric cancers including Ewing sarcoma, neuroblastoma, rhabdomyosarcoma, hepatoblastoma and medulloblastoma, the protracted administration schedule of IRN-IV is costly and inconvenient thereby negatively impacting patients’ quality of life. Oral regimens utilizing IRN-IV have been developed and implemented with favorable tumor responses (Wagner. ClinSarcRes, 2015). Unfortunately, the palatability of the IRN-IV is poor, leading to reduced compliance. Development of an advanced oral formulation to improve tolerability and patient compliance is an important unmet need. VAL-413 is a novel formulation developed to improve the palatability of oral irinotecan. This ongoing Phase 1-2a multi-center clinical trial seeks to examine the safety and tolerability of this novel formulation and assess pharmacokinetics compared to the already established oral regimen. Methods: Eligibility: Up to 20 patients ≥ 1 year of age or ≤ 30 years of age with recurrent pediatric solid tumors and adequate bone marrow, renal and liver function, for whom irinotecan therapy is a treatment option will be enrolled. Trial Design: Two different dose levels of VAL-413, 90mg/m2/day or 110mg/m2/day are being studied in combination with fixed-dose temozolomide (100mg/m2/day) using a standard 3 + 3 phase I design. In the event a dose of 90 mg/m2/day is not tolerable due to toxicity, a lower dose of 75 mg/m2/day may be implemented. Treatment: During the first cycle of treatment, each patient will receive 4 daily doses of VAL-413 and one daily dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO). During all subsequent cycles, only VAL-413 will be given with temozolomide in 5-day courses administered every 21 days, as tolerated. Outcome Measures: Toxicity is assessed by NCI CCTCAEv5; tumor response is assessed by RECIST 1.1. A taste survey instrument will assess palatability of VAL-413 vs. IRN-IVPO; comparative intrapatient pharmacokinetics of irinotecan and its metabolites is assessed. This trial is ongoing (CT.gov: NCT04337177) and has completed two planned dose cohorts, with no dose limiting toxicity observed to date. A Phase 2 expansion is underway. Ongoing pharmacokinetic observations demonstrate similarity for the Orotecan (VAL-413) formulation and i.v. irinotecan given orally for both the parent compound and its active metabolites. Citation Format: Jeffrey Bacha, Dennis Brown, James Geller, Javier Oesterheld, Patrick Thompson, Aerang Kim, Meghann McManus, Sarath Kanekal, Markos Leggas, Lorena Lopez, Neil Sankar, Noymi Yam, Lars Wagner. A multicenter phase 1-2a clinical study of Orotecan® (oral irinotecan HCl, VAL-413) in patients with recurrent pediatric solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB266.