Abstract B012: KinLET: A phase I dose-finding, safety and pharmacokinetic trial of [177Lu]Lu-edotreotide for the treatment of somatostatin receptor positive tumors in the pediatric population aged 2 to less than 18 years old

Abstract Radiopharmaceutical therapy (RPT) with [177Lu]Lu-edotreotide can selectively target somatostatin receptor positive (SSTR-positive) tumors. The COMPETE trial demonstrated that [177Lu]Lu-edotreotide significantly improved progression-free survival compared to everolimus in adult patients with inoperable, progressive Grade 1 or Grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and was well-tolerated with a favorable safety profile. GEP-NETs occur in pediatric patients but are very rare. [177Lu]Lu-dotatate, another somatostatin receptor (SSTR)-targeting RPT, was recently approved by the United States Food and Drug Administration (FDA) for children 12 years and older with GEP-NETs, but this class of agents has not been systematically studied across the pediatric age range or range of pediatric tumors expressing SSTRs. Pediatric SSTR-positive tumors include, but are not limited to, neuroendocrine tumors (NETs), central nervous system tumors, lymphoma, rhabdomyosarcoma, peripheral primitive neuroectodermal tumors and gastrointestinal stromal tumors. The KinLET trial is designed to determine the appropriate dose for pediatric patients based on the safety profile and the pharmacokinetics (PK) of [177Lu]Lu-edotreotide targeted RPT in patients with SSTR-positive tumors across the pediatric age range. Safety as monotherapy and following standard of care, PK, tumor and target organ dosimetry, and preliminary antitumor activity by tumor type will be assessed. Dosimetry will be measured by single-photon emission computed tomography/low dose computed tomography imaging, whole body planar imaging and blood radioactivity concentration measurements at various time points post infusion of [177Lu]Lu-edotreotide. Up to 6 cycles of intravenous infusion of [177Lu]Lu-edotreotide, co-infused with amino acid solution, is administered at 8 weeks (± 2 weeks) interval with starting dose of 100 MBq/kg (for first age cohort) or up to 7.5 GBq/75 kg per cycle. Dosimetry and toxicity are evaluated after each cycle to ensure that the cumulative absorbed dose for kidney and bone marrow remains less than 23 Gy and 2 Gy, respectively. Intervals between cycles may be further increased for recovery from dose-modifying toxicity. At least 20 participants are planned to be included in three sequential age cohorts with a minimum of 6 participants in each age cohort: (1) ≥ 12 to < 18 years old; (2) ≥ 6 to < 12 years old; (3) ≥ 2 to < 6 years old. Safety and dosimetry from the previous cohort will determine the opening of the 2nd and 3rd cohorts respectively. Currently the trial is approved in United States, Spain and Italy. The rationale for the dose and regimens is based on previously established studies in adults with advanced NETs and an in-silico extrapolation of the dosimetry observed in adult patients from the literature and preliminary data from COMPETE study. Patient recruitment will be an important element of KinLET trial, considering comparatively low incidence of SSTR-positive tumors and extreme rarity of GEP-NETs in the pediatric population. Citation Format: Theodore Laetsch, Raya Saab, Helen Nadel, Nino Shavdia, Serhii Melnyk, Shahanaz Rahman, Cristina Mata Fernández. KinLET: A phase I dose-finding, safety and pharmacokinetic trial of [177Lu]Lu-edotreotide for the treatment of somatostatin receptor positive tumors in the pediatric population aged 2 to less than 18 years old [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr B012.