Prostate cancer is the second most frequent and leading cause of cancer-related death in males worldwide.1 While early detected localized prostate cancer can be treated with radiotherapy and surgery, some are likely to develop metastatic disease.2
Standard initial treatment for patients with metastatic disease is androgen deprivation therapy (ADT), which aims to produce chemical castration, lowering testosterone levels by blocking gonadotrophin (LH and FSH) production by the pituitary gland.3 Once the patient progresses to ADT, metastatic castration resistant prostate cancer (mCRPC) patients are treated with agents that block androgen biosynthesis or the receptor.4 Ultimately, however, these patients experience disease progression. Currently, a cure remains elusive for this advanced stage of the disease with survival periods averaging 9-13 months, contributing to its status as second cause of male cancer related deaths.5
ITM-22 (225Ac-PSMA-TTM*) is an innovative agent for Targeted Radionuclide Therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) who express Prostate-specific membrane antigen (PSMA). Developed by ITM, in collaboration with an academic partner, ITM-22 consists of two molecular components – the therapeutic radioisotope Actinium-225, an alpha particle emitter that provides a high energy at close range and secondly, a variant of the tumor targeting molecule PSMA that has the potential to increase the retention and accumulation of the therapeutic candidate in the tumor. PSMA is a transmembrane glycoprotein that shows increased expression in almost all prostate cancer cells, with the expression further increasing in the hormone-refractory state.6 Results of clinical trials have already demonstrated the potential of Targeted Radionuclide Therapy in prostate cancer.7 Thereby, Lutetium-177 labeled molecules have shown favorable efficacy and safety results in patients with mCRPC. 177Lu, being a beta emitter with relatively lower linear energy transfer, mostly causes the easy-to-repair single stranded DNA breaks.8 The alpha particle emitter 225Ac, with a high linear energy transfer, on the contrary, induces blunt-ended double-stranded breaks.9 ITM is optimistic for the potential of ITM-22 in future PSMA studies.
* TTM = Tumor Targeting Molecule
1 Bray F et al., 2018, Global cancer statistics 2018; 68(6):394-424
2 Horwich A et al., 2010, ESMO Guidelines Working Group; 21 Suppl 5:v129-v133.
3 Crawford ED et al., 2019, Androgen-targeted therapy in men with prostate cancer;22(1):24-38.
4 Beer TM et al., 2014, Enzalutamide in metastatic prostate cancer before chemotherapy; 371(5):424-433.
5 He L et al., 2020, Metastatic castration-resistant prostate cancer; 99(15):e19760.
6 Bouchelouche K et al., 2010, Prostate specific membrane antigen - a target for imaging and therapy with radionuclides; 9(44):55-61.
7 Sartor O et al., 2021, Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer; 385(12):1091-1103.
8 Kratochwil C et al., 2020, Patients Resistant Against PSMA-Targeting α-Radiation Therapy Often Harbor Mutations in DNA Damage-Repair-Associated Genes; 61(5):683-688.
9 Satapathy S et al., 2021, Evolving role of 225Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer - a systematic review and meta-analysis; 24(3):880-890.
Please note: ITM-22 (225Ac-PSMA-TTM*) is not authorized for marketing in any country at this time.