Lutetium Lu 177 Edotreotide dose-finding for children with SSTR-positive tumors

A Multicenter, Open-label, Interventional Phase I Trial to Determine the Dose and Evaluate the Pharmacokinetics (PK) and Safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as Monotherapy or Following Standard of Care (SoC) for the Treatment of Somatostatin Receptor-positive Tumors in the Pediatric Population (KinLET).

This test gives Lutetium Lu 177 Edotreotide to children ages 2 to under 18 with somatostatin receptor–positive tumors to find a safe pediatric dose and see how the drug behaves in the body.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 24 Months to 18 Years
• Sex: All
• Sponsor: ITM Solucin GmbH (Industry-sponsored)
• Drugs / interventions: CAR-T, radiation
• Locations: 5 sites (Philadelphia, Pennsylvania and 4 other locations)
• Trial ID: NCT06441331 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label dose-finding trial enrolls pediatric participants (ages 2 to <18) with recurrent, progressive, or refractory somatostatin receptor (SSTR)-positive neuroendocrine, CNS, lymphoma, or other solid tumors. Eligible tumors must show SSTR protein by immunohistochemistry and uptake on somatostatin receptor imaging higher than liver uptake. Participants receive intravenous Lutetium Lu 177 Edotreotide every 8 weeks for up to six doses (about 48 weeks total), with supportive amino acid solution as part of administration. The study focuses on defining the appropriate pediatric dose, characterizing pharmacokinetics, and monitoring safety and tolerability when given alone or following standard-of-care therapy.

Who should consider this trial

Good fit: Children aged 2 to under 18 with recurrent, progressive, or refractory SSTR-positive NETs, CNS tumors, lymphoma, or other solid tumors who show SSTR expression by immunohistochemistry and uptake on somatostatin receptor imaging and have recovered from prior treatment toxicities are the ideal candidates.

Not a fit: Patients whose tumors do not express SSTRs or lack uptake on SSTR imaging, those with unresolved toxicities from prior treatments, or those unable to travel to a participating center are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the treatment could provide a targeted radioactive therapy option that helps control SSTR-positive tumors in children who have limited standard options.

How similar studies have performed: Similar adult trials using 177Lu-labeled somatostatin analogs (for example, 177Lu-DOTATATE) have shown clinical benefit in SSTR-positive neuroendocrine tumors, but pediatric data for Lutetium Lu 177 Edotreotide are limited, so this work builds on adult success but is relatively untested in children.

Eligibility criteria

Key Inclusion Criteria:

* Participants aged ≥ 2 years and \< 18 years
* Confirmed diagnosis somatostatin receptor-positive (SSTR-positive) disease.
* Tumor which is relapsed or is refractory to at least one line of previous therapy
* Positive SSTR protein expression confirmed by immunohistochemistry of a tumor histology sample
* Radioactivity uptake within the primary tumor or metastatic tumor sites measured by locally available SRIs ( 111In-based, 99mTc-based, or 68Ga-based SSTR single-photon emission computed tomography (SPECT)/ computed tomography (CT) or positron emission tomography (PET)/CT imaging, which is higher than the liver uptake)
* Participants must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria, excluding alopecia, stable treated electrolyte abnormalities on replacement and stable treated hypothyroidism) of all prior treatment modality prior to entering this trial
* In case of sequential treatment followed by SoC or prior therapy, washout period applies before starting targeted RPT

Screening Consent Participant/legal guardian is willing to sign a screening consent. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.

Key Exclusion Criteria:

* Known hypersensitivity to Lutetium Lu 177 Edotreotide, DOTA/Edotreotide, or excipients
* Previous history of acute leukemia unless in remission for at least two years
* Extensive bone/bone marrow involvement as per Investigator's judgement unless peripheral blood stem cells (PBSC) are available at a minimum of 2.5x106 CD34+ cells/kg
* Patients who have received previous systemic targeted RPT
* Previous treatment with metaiodobenzyl guanidine (MIBG) if the predicted overall exposure is expected to exceed 2 Gy (gray) to the bone marrow or 23 Gy to the kidney.
* Previous treatment with external beam radiation therapy (EBRT) if the predicted overall exposure is expected to exceed more than 2 Gy to the bone marrow or 23 Gy to the kidney.
* Previous treatment with oncologic immune vaccine or CAR-T cell therapy
* Bulky disease in the CNS
* Presence of severe renal, hepatic, electrolyte, cardiovascular, or hematological dysfunction
* Participants who have received a live-attenuated vaccine up to four weeks prior to enrolment
* Pregnant or breastfeeding women.
* Other known malignancies.
* Serious non-malignant disease.

Where this trial is running

Philadelphia, Pennsylvania and 4 other locations

• The Children's Hospital of Philadelphia (CHOP) — Philadelphia, Pennsylvania, United States (Recruiting)
• University of Texas - MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Gustave Roussy Cancer Campus — Villejuif, France (Recruiting)
• Hospital Universitario Vall d'Hebron - Oncología Médica — Barcelona, Spain (Recruiting)
• Hospital General Universitario Gregorio Marañón — Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Shahanaz Rahman

Conditions Somatostatin Receptor Positive; NETs; Lymphoma; Solid Tumor; CNS Tumors; Rhabdomyosarcoma; Peripheral Primitive Neuroectodermal Tumor; GIST