Orano Med, a clinical stage radiopharmaceutical company, today announced that the first patient has been dosed in a Phase 1 trial of the alpha radioligand therapy with lead-212, 212Pb-GRPR, in patients with advanced solid tumors that
express gastrin-releasing peptide receptor (GRPR). 212Pb-GRPR is the first targeted alpha therapy (TAT) targeting GRPR, a protein located on the surface of cells that is highly expressed in prostate cancer, lung cancer, breast cancer
and other solid tumors.
“Dosing the first patient in our Phase I 212Pb-GRPR clinical trial is a key development milestone for Orano Med in our strategy to develop a pipeline of alpha radiopharmaceuticals targeting difficult to treat cancers,” said Julien Dodet, Chief Executive Officer.
The short-range cancer cell killing capabilities of alpha-emitting radioisotopes could mean there is limited toxicity to surrounding healthy cells. Based on promising preclinical results with 212Pb-GRPR, we believe that this first alpha therapy targeting GRPR could significantly improve outcomes for cancer patients who have exhausted other therapies.
212Pb-GRPR is being evaluated in an ongoing, multi-center, single arm, non-randomized, open-label basket trial that will enroll approximately 30 patients with advanced solid tumors. It includes a dose escalation phase followed by an expansion phase. The primary endpoint is to evaluate the safety and tolerability of 212Pb-GRPR. Exploratory efficacy endpoints include objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using RECIST v1.1 criteria. Additional information about the trial, which is recruiting patients, can be found on clinicaltrials.gov: NCT 05283330.
“We are convinced that targeted alpha therapies, such as 212Pb-GRPR, are the future of radiopharmaceutical therapies, providing an increased cytotoxic potential against cancer cells and the ability to improve treatments in areas of high unmet needs. We were excited about the success of recent beta emitters but believe that alpha radiopharmaceutical therapies will be the next more effective game changer, which will advance the field significantly,” said Michael Morris, MD, Founder & Medical Director of Advanced Molecular Imaging and Therapy, the specialist center where the first patient was dosed.
About Targeted Alpha Therapy
Targeted alpha therapy (TAT) relies on a simple concept: combining the ability of biological molecules to target cancer cells with the short-range cell-killing capabilities of alpha-emitting radioisotopes. Alpha decay consists of the emission of a helium
nucleus (alpha particle) together with very high linear energy transfer and a range emission of only few cell layers, resulting in irreparable double strand DNA breaks in cells adjacent only to area of alpha emission. This approach results in an increased
cytotoxic potential toward cancer cells while limiting toxicity to nearby healthy cells. As a result, alpha emitters are considered as the most powerful payloads to be found for targeted therapies.
Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled receptor of the family of bombesin receptors. Its ligand, gastrin-releasing peptide (GRP), is a peptide that regulates numerous physiologic functions of the gastrointestinal and central
nervous systems, and is overexpressed in a number of cancers, such as prostate, breast, and lung. Oncology research has made tremendous progress in recent years in treatment of these cancers. However, in the 2020’s, around 25,000 patients are
expected to be diagnosed with metastatic prostate cancer in the United States, with an average 5-year survival rate of 30%. In breast cancer, around 50,000 patients are expected to have metastatic tumors, with an average 5-year survival rate of 27%.
About Orano Med
Orano Med is a nuclear biotech company developing innovative radiopharmaceutical therapies in oncology. Orano Med has developed new processes for producing lead-212 (212Pb), a rare radioactive isotope used in targeted alpha therapy (TAT),
an innovative and promising approach of nuclear medicine that recognizes and destroys cancer cells while limiting the impact on nearby healthy cells. In addition to the 212Pb-GRPR trial, Orano Med is also conducting the phase II clinical
trial of 212Pb-DOTAMTATE, which could offer a therapeutic alternative for the treatment of metastatic neuroendocrine tumors.