Orano Med has advanced its long-running collaboration with Roche as both companies prepare to take a two-step pretargeted radioimmunotherapy into human trials. The partners have spent several years evaluating the approach in preclinical studies and now plan to progress the therapy, which uses lead-212 (212Pb), into phase 1 testing in 2026. Orano Med will manufacture the isotope through its production sites in France and the US.

The work centres on a sequential targeting method known as two-step pretargeted radioimmunotherapy. The technique relies on a tumour-specific antibody administered first, which then binds a 212Pb-bearing radioligand delivered afterwards. The companies aim to exploit the short half-life of 212Pb by ensuring the isotope arrives at the tumour only after the antibody has accumulated and excess circulating antibody has cleared.

Nicolas Maes, chief executive officer of the Orano Group, said: “We are very pleased about the progress made in collaboration with Roche for the development of a potential new treatment approach for cancer patients.” He added that the milestone reflects the group’s long-term plan to build a pipeline of 212Pb-targeted alpha therapies supported by the organisation’s access to thorium-232, required for isotope production.

Julien Torgue, chief scientific officer of Orano Med, said: “The application of two-step pretargeted radioimmunotherapy represents a potentially game-changing advancement in radioligand therapies and cancer treatment more broadly.” He noted that preclinical work has shown strong activity with lower off-target uptake, adding that the approach could support more selective tumour targeting if results translate clinically.

Under the collaboration, Roche and Orano Med will evaluate the therapy in cancers expressing carcinoembryonic antigen. CEA is overexpressed across several solid tumours, including colorectal, pancreatic and gastric cancers, as well as certain lung cancers. It shows low expression in most healthy tissues, which has established it as a focus for antibody-based therapies and radioligand development.

The phase 1 study, to be sponsored by Roche, is expected to start in the first half of 2026. The trial will be the first clinical test for this two-step 212Pb platform and is planned as the foundation for a broader alpha radioimmunotherapy strategy at Orano Med.

The two-step method builds on earlier radioligand modalities by separating tumour localisation from radioisotope delivery. Unlike three-step pretargeting, the new design does not require an intermediate clearance step to remove residual antibody from circulation. According to the partners, this simplifies implementation and supported improved efficacy and tolerability in preclinical testing. Studies showed high uptake in CEA-positive tumours, fast clearance of unbound 212Pb-DOTAM and limited accumulation in organs such as the kidney.