1122TiP - A phase II trial to evaluate the safety and dosimetry of [¹⁷⁷Lu]Lu-DOTA-TATE in adolescent patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), pheochromocytomas and paragangliomas (PPGLs)

Background

In the paediatric population, there are limited approved therapies for GEP-NETs and PPGLs. SSTR subtype 2 is overexpressed by GEP-NET and PPGL tumours and, therefore, it is a relevant target for peptide receptor radionuclide therapy with [¹⁷⁷Lu]Lu-DOTA-TATE. [¹⁷⁷Lu]Lu-DOTA-TATE is approved for the treatment of adult patients with SSTR-positive GEP-NETs. It has shown efficacy in a number of trials in adult patients but there have been no Advanced Accelerator Applications-sponsored paediatric clinical trials in GEP-NETs and PPGLs to date. The treatment of adolescents with GEP-NETs and PPGLs represents a significant unmet need, providing a strong rationale to evaluate [¹⁷⁷Lu]Lu-DOTA-TATE in these patients.

Trial design

This multicentre, phase II, open-label, single-arm study is designed to evaluate the safety and dosimetry of [¹⁷⁷Lu]Lu-DOTA-TATE in adolescent patients (12 to <18 years old) with advanced, inoperable, SSTR-positive GEP-NETs (grade 1 or 2, well differentiated) in the primary cohort and PPGLs in the exploratory cohort. Eligible patients will receive four cycles of [¹⁷⁷Lu]Lu-DOTA-TATE (activity per cycle: 7.4 GBq), administered every eight weeks. After the last dose, patients will be followed up for five years. Radiation dosimetry and pharmacokinetic (PK) assessments will be done after the first [¹⁷⁷Lu]Lu-DOTA-TATE administration. Safety assessments will be performed regularly after each cycle. Primary endpoints are target organ absorbed radiation dose and incidence of adverse events (AEs) after the first cycle. Secondary endpoints are incidence of AEs within six months (short-term follow-up) and five years (long-term follow-up) after the last dose, and PK and dosimetry compared with predicted values. Efficacy will be assessed as an exploratory objective, including objective response rate, progression-free survival and overall survival in both cohorts. This study will enrol at least eight patients with GEP-NETs and as many patients with PPGLs as possible across multiple sites in Europe and North America (NCT04711135).

Clinical trial identification

NCT04711135; 4 November 2020.

Editorial acknowledgement

The authors thank Summer Browne (NexGen Healthcare Communications) for writing and editorial assistance, funded by Advanced Accelerator Application, A Novartis Company. Advanced Accelerator Application, A Novartis Company reviewed the abstract for scientific accuracy but had no significant input into the content.

Legal entity responsible for the study

Advanced Accelerator Applications, a Novartis Company.

Funding

Advanced Accelerator Applications, a Novartis Company.

Disclosure

F. Brouri, I. Folitar: Financial Interests, Institutional, Full or part-time Employment: Advanced Accelerator Applications, A Novartis company. All other authors have declared no conflicts of interest.