Phase 3 to Investigate How Survival Outcomes Are Impacted by 177Lu-Edotreotide Treatment

The phase 3 COMPOSE study will evaluate the efficacy of lutetium ¹⁷⁷Lu-edotreotide (¹⁷⁷Lu-edotreotide) versus best standard of care in well-differentiated aggressive grade 2 and grade 3 somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs), according to a press release by ITM Isotope Technologies. ¹

¹⁷⁷Lu-edotreotide is composed of the medical radioisotope no-carrier-added n.c.a. lutetium-177 and edotreotide, a synthetic form of the peptide hormone somatostatin which targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and delivers lutetium-177 directly onto the disease neuroendocrine cells. This causes it to accumulate in the tumor site.

The COMPOSE trial (NCT04919226) has a target enrollment of 202 participants and an estimated completion date of September 2026. The primary end point of the trial is progression-free survival. The secondary end point is overall survival.²

During the study, patients will be randomized 1:1 into an experimental or control arm. During the control arm, patients will receive ¹⁷⁷Lu-edotrerotide and an amino-acid solution. During the control arm, the best standard of care treatment will be used. Investigators can pick between 3 options:

• Capecitabine and Temozolomide (Temodar)
• Everolimus (Afinitor) 10 mg
• Folinic acid, fluorouracil, and oxaliplatin

“The most common form of NETs is gastroenteropancreatic and often develops metastatic disease, limiting treatment options. N.c.a. ¹⁷⁷Lu-edotreotide has previously shown a favorable safety and efficacy profile in GEP-NETs and with COMPOSE we aim to also make it available to late-stage patients suffering from this hard-to-treat cancer indication,” said Steffen Schuster, CEO of ITM, in a press release. “We look forward to the opportunity of introducing our phase III COMPOSE trial to the global scientific community at the NANETS symposium, a key oncology event that features leading research, education, and emerging practices on NETs.”

In order to participate in the study, patients must be 18 years of age or older, have a confirmed diagnosis of unresectable, well-differentiated gastroenteropancreatic NETs, measurable disease, and be somatostatin receptor positive. Patients who have received prior peptide receptor radionuclide therapy, any major surgery within 4 weeks prior to randomization, other known malignancies, serious non-malignant disease, renal, hepatic, cardiovascular, or hematological organ dysfunction, or are breastfeeding are unable to participate.

In addition to being studied in gastroentreropancreatic NETs, ¹⁷⁷Lu-edotreotide is also being studied in the phase 3 COMPETE trial (NCT03049189). This trial is looking at the agent in combination with everolimus for the treatment of inoperable, progressive, somatostatin receptor-positive, neuroendocrine tumors of gastroenteric or pancreatic origin.

_REFERENCES:

_{1.ITM introduces second phase III trial, COMPOSE, with n.c.a. Lutetium-177-edotreotide for neuroendocrine tumors at NANETS Annual Symposium 2021. ITM. News release. November 3, 2021. Accessed November 3, 2021. https://bit.ly/3GJY9Jr}

_{2.Lutetium 177Lu-edotreotide versus best standard of care in well-differentiated aggressive grade-2 and grade-3 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) - COMPOSE (COMPOSE). ClinicalTrials.gov. Accessed November 3, 2021. https://bit.ly/3q4TPOH}