FDA Grants Fast Track Designation to ITM-11 for Gastroenteropancreatic Neuroendocrine Tumors

The FDA has granted a fast track designation to ¹⁷⁷Lu-edotreotide (ITM-11) for use as a potential therapeutic option in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to an announcement from ITM Isotype Technologies Munich SE.¹

ITM-11 is comprised of the octreotide-derived somatostatin analog edreotide (Dotatoc) and no-carrier lutetium-177 chloride, which is a beta-emitting therapeutic radioisotope.² Edreotide contains DOTA and TOC and binds with high affinity to somatostatin receptors; when labeled with ¹⁷⁷Lu, it also maintains its receptor-binding properties and physiological function. Once bound to those receptors in vivo, the agent is internalized and retained by cancer cells. The isotope then releases cytotoxic medium-energy beta particles into the soft tissue upon decay.

“We are dedicated to helping people living with hard-to-treat cancers through our research and development of innovative treatments,” Steffen Schuster, chief executive officer of ITM, stated in a press release. “Receiving fast track designation provides us the opportunity to work closely with the FDA to optimize and accelerate the final stages of development for ITM-11, bringing our radiotherapeutic to GEP-NETs patients as fast as possible.”

The designation allows for the company to hold more interactions with the regulatory agency to discuss the developmental pathway for the investigative agent. With fast-track status, a rolling review of the new drug application for ITM-11 will also be permitted.

The safety and efficacy of the radiopharmaceutical candidate vs standard treatment is being explored in patients with inoperable, progressive, grade 1 and 2, as well as aggressive grade 2 and 3, somatostatin receptor (SSTR)–positive GEP-NETs as part of the phase 3 COMPETE (NCT03049189) and COMPOSE (NCT04919226) trials.

The international, prospective, randomized, controlled, open-label, multicenter COMPETE trial is enrolling patients with inoperable, progressive, SSTR-positive, grade 1 and 2 GEP-NETs.³ Patients will be randomly assigned to receive up to 4 cycles of ITM-11 every 3 months or until progressive disease or everolimus (Afinitor) at 10 mg daily for 24 months or until disease progression. The primary objective of the trial is to evaluate progression-free survival (PFS). Secondary end points include safety, objective response rate, and overall survival (OS) at 5 years.

The prospective, randomized, controlled, open-label, multicenter COMPOSE trial enrolled patients with a histologically confirmed diagnosis of unresectable, well-differentiated GEP-NETs and SSTR positivity who were at least 18 years of age.⁴ If patients previously received peptide receptor radionuclide therapy (PPRT), underwent any major surgery within 4 weeks before randomization, had other known malignancies, a serious non-malignant disease, or renal, hepatic, cardiovascular, or hematological organ dysfunction, they were excluded.

The study aims to enroll 202 patients and randomly assign them 1:1 to receive PRRT with ITM-11 for 6 cycles or investigator’s choice of best standard care, which could include chemotherapy (CAPTEM or FOLFOX) or everolimus.

The primary end point of the trial is PFS, which will be evaluated every 12 weeks until progressive disease or death. OS will serve as a key secondary end point, and that will be examined for up to 2 years following disease progression.

In January 2022, the company announced that the first patient was treated on the trial.⁵

“Targeted radionuclide therapy is a promising therapeutic concept that enables a precise intervention both for the primary tumor as well as for metastases,” Professor Walter, principal investigator of COMPOSE, of the Hospices civils de Lyon, in France, stated in a past press release. “As such, we hope to build upon previous promising data to demonstrate in COMPETE and COMPOSE that targeted radionuclide therapy with ITM-11 has the potential to improve treatment outcomes and quality of life for a broad patient population.”

References

1. ITM receives FDA fast track designation for radionuclide therapy candidate ITM-11 (n.c.a. 177Lu-edotreotide) in neuroendocrine tumors (GEP-NETs). News release. ITM Isotope Technologies Munich SE. October 27, 2022. Accessed October 28, 2022. https://bit.ly/3W5XgSW
2. ITM-11 for neuroendocrine tumors (GEP-NETs). ITM Isotope Technologies Munich SE. Accessed October 28, 2022. https://bit.ly/3zrKch6
3. ITM presents design for ongoing phase III COMPETE trial with n.c.a. 177Lu-edotreotide at AACR Annual Meeting 2021. News release. ITM AG. April 10, 2021. Accessed October 28, 2022. https://bwnews.pr/3U3stV6
4. Halfdanarson TR, Reidy D, Vijayvergia N, et al. Pivotal phase III COMPOSE trial will compare 177Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors. J Clin Oncol. 2022;40(suppl 4):TPS514. doi:10.1200/JCO.2022.40.4_suppl.TPS514
5. ITM announces first patient treated in second phase III trial, COMPOSE, with ITM-11 (n.c.a. 177Lu-edotreotide) for treatment of neuroendocrine tumors. News release. ITM Isotope Technologies Munich SE. January 25, 2022. Accessed October 28, 2022. https://bwnews.pr/3gTUccm