FDA Grants Breakthrough Therapy Designation to Novel Agent in GEP-NETs

Tumor microenvironment background with cancer cells, T-Cells, nanoparticles, molecules, and blood vessels. Oncology research concept: © ratatosk - stock.adobe.com

• ²¹²PB-DOTAMTATE (AlphaMedixTM) received breakthrough therapy designation from the FDA, signifying the drug's potential to significantly improve over existing treatments for inoperable or metastatic, somatostatin receptor (SSTR)-expressing gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
• The drug demonstrated a 62.5% overall response rate (ORR) in a phase 1 study (NCT03466216).
• If positive results continue, 212PB-DOTAMTATE could offer a new treatment avenue for this challenging condition.

The FDA has granted breakthrough therapy designation to ²¹²PB-DOTAMTATE for the treatment of patients with inoperable or metastatic, progressive SSTR-expressing GEP-NETs who have not received treatment with a peptide receptor radionuclide therapy (PPRT).¹

The breakthrough therapy designation is designed to expedite development and review of agents targeting serious conditions where early data demonstrates a potential improvement over existing therapies.

“The FDA's breakthrough therapy designation underscores [²¹²PB-DOTAMTATE’s] potential as an innovative treatment that could redefine how patients with neurendocrine tumors are treated. We believe that [²¹²PB-DOTAMTATE] has potential to demonstrate substantial benefit over currently FDA approved PRRT with beta-particle emitters for patients with metastatic or inoperable SSTR-expressing GEP-NETs,” said Ebrahim Delpassand, MD, chairman and chief executive officer of RadioMedix, in a press release.

The designation of ²¹²PB-DOTAMTATE, an SSTR-targeting peptide complete radiolabeled with lead-212 generating alpha particles, is supported by phase 1 and ongoing phase 2 clinical trials (NCT05153772).

In the phase 1 study, ²¹²PB-DOTAMTATE delivered an ORR of 62.5% for PRRT- and lutetium Lu 177 dotatate (Lutathera)-naive patients. Topline data from the phase 2 trial is expected in mid-2024; however, investigators note that the target response rate has already been achieved. 

“The FDA's decision is a great news for patients suffering from this illness, and an important milestone to expedite the development of this new therapy,” added Delpassand, in the press release.

About the Phase 2 Trial of ²¹²PB-DOTAMTATE in GEP-NETs

The study has an estimated enrollment of 68 patients who are aged 18 or older with confirmed SSTR receptors on all lesions and have progressive disease following somatostatin analog treatment.² Patients who are PRRT-naive should have documented disease progression within 12 months of study enrollment. Patients must have an ECOG performance status of 0 to 2, a life expectancy of at least 12 weeks, and adequate bone marrow capacity and organ function within 3 weeks of treatment initiation.

Patients are not eligible to enroll if they have received regional hepatic radionuclide therapy within 4 months of study enrollment, nonradioactive hepatic therapy within 6 months of study enrollment, a known hypersensitivity to the study agents, a history of myelodysplastic syndrome, uncontrolled congestive heart failure, or uncontrolled diabetes mellitus.

The primary end points are ORR and incidence of treatment-related adverse events. Secondary end points include median progression-free survival, overall survival, time to tumor progression, and health-related quality of life.

REFERENCES:

1. RadioMedix and Orano Med received FDA breakthrough therapy designation for AlphaMedixTM in gastroenteropancreatic neuroendocrine tumors first targeted alpha therapy to receive a breakthrough therapy designation. News release. RadioMedix, Inc. February 12, 2024. Accessed February 12, 2024. http://tinyurl.com/3wy3c7j8

2. Targeted alpha-emitter therapy of PRRT naive and previous PRRT neuroendocrine tumor patients (ALPHAMEDIX02). ClinicalTrials.gov. Updated October 23, 2023. Accessed February 12, 2024. https://www.clinicaltrials.gov/show/NCT05153772