lutetium (177Lu) girentuximab + peposertib

**Lutetium (177Lu) girentuximab + peposertib** is an experimental therapeutic combination being investigated for the treatment of advanced solid tumors, particularly clear cell renal cell carcinoma (ccRCC) and other CAIX-expressing tumors. Lutetium (177Lu) girentuximab is a radioimmunoconjugate that consists of girentuximab, a monoclonal antibody targeting carbonic anhydrase IX (CAIX), linked to the radioactive isotope lutetium-177. It selectively delivers β-radiation to CAIX-expressing tumor cells, inducing DNA double-strand breaks. **Peposertib** is a selective, orally available inhibitor of DNA-dependent protein kinase (DNA-PK), a key enzyme involved in the nonhomologous end-joining pathway of DNA double-strand break repair. Peposertib impedes DNA repair, thus sensitizing tumor cells to DNA-damaging agents like radiotherapy. Together, the combination is designed to synergize: lutetium (177Lu) girentuximab delivers targeted DNA damage, while peposertib blocks repair, leading to enhanced antitumor efficacy at lower radiation doses. This regimen is being co-developed by Telix Pharmaceuticals (TLX250, lutetium (177Lu) girentuximab) and Merck KGaA (peposertib), with ongoing clinical investigations in phase 1/2 for advanced CAIX-expressing solid tumors, including renal cell carcinoma[1][3][7][9].

Other names

177Lu-TLX250 + peposertib