Orano Med and Roche Advance Novel Two-Step Radioimmunotherapy Targeting CEA-Positive Cancers
核心洞察
Orano Med (搜索) and Roche are advancing their two-step pretargeted radioimmunotherapy (PRIT) using lead-212 into clinical development, with a Phase 1 trial expected to begin in the first half of 2026.
The innovative approach targets carcinoembryonic antigen (搜索) (CEA (搜索)) in colorectal, pancreatic, gastric, and certain lung cancers, eliminating the need for an intermediate clearance step used in traditional PRIT methods.
Preclinical studies demonstrated strong efficacy and improved safety profile, with substantial tumor uptake and rapid clearance of unbound radioligand, potentially offering a safer alternative to conventional radioligand therapies.
Orano Med (搜索) and Roche have announced their collaboration on a novel two-step pretargeted radioimmunotherapy (PRIT) approach is advancing into clinical development, marking a significant milestone in targeted alpha therapy for cancer treatment. The innovative treatment uses lead-212 (212Pb), a rare alpha-emitting radioisotope, to target carcinoembryonic antigen (搜索) (CEA (搜索))-positive tumors with enhanced precision and safety.
Revolutionary Two-Step Approach
The novel PRIT technology represents a departure from conventional radioligand therapies by separating the targeting and radiation delivery into two distinct steps. According to Julien Torgue, Chief Scientific Officer of Orano Med (搜索), "Instead of delivering radiation and targeting vector together, the novel technique separates the process into two precise steps: first, allowing time for antibodies to accumulate on the tumor, and then capturing the alpha particle emitting radioactive isotope lead-212, which allows for the precise targeting of cancer cells while sparing healthy tissue."
This sequential approach first administers a tumor-targeting bispecific antibody, followed by a radioligand carrying the radioactive payload. The delay allows the bispecific antibody necessary time to accumulate on tumor cells while unbound radioligand is rapidly cleared, enabling highly specific antibody targeting while remaining compatible with the relatively short half-life of 212Pb (10.6 hours).
Targeting CEA-Positive Cancers
The collaboration focuses on developing a therapeutic solution targeting carcinoembryonic antigen (搜索) (CEA (搜索)), a cell surface glycoprotein overexpressed in several cancer types. CEA serves as a marker for colorectal, pancreatic, and gastric cancers, as well as certain lung cancers - malignancies for which current therapeutic options are often limited or insufficient to meet patients' needs. The restricted expression of CEA in normal tissues makes it a suitable target for antibody-based therapies and radioimmunotherapy.
Promising Preclinical Results
Preclinical studies have confirmed both proof of mechanism and therapeutic efficacy of the two-step PRIT approach. The studies demonstrated favorable biodistribution with substantial uptake in CEA (搜索)-positive tumors and rapid clearance of unbound 212Pb-DOTAM (搜索), with limited accumulation in kidneys and other organs. These results confirm the excellent 212Pb tumor specificity and its high potential to significantly delay tumor growth.
The new approach developed by Roche and Orano Med (搜索) eliminates the need for an intermediate clearance step traditionally required in PRIT methods. This strategy combines a complementary bispecific antibody pair with chelated 212Pb, demonstrating both high efficacy and improved tolerability in preclinical studies compared with three-step PRIT approaches.
Clinical Development Timeline
A Roche-sponsored Phase 1 clinical trial is expected to start in the first half of 2026, initiating the development of a broader platform dedicated to alpha radioimmunotherapies. This advancement underscores Orano Med (搜索)'s global leading position in the field of targeted alpha therapies.
Manufacturing and Strategic Positioning
Orano Med (搜索) will be responsible for manufacturing 212Pb, utilizing its industrial manufacturing platform in France and the US. Nicolas Maes, Chief Executive Officer of the Orano Group (搜索), noted: "Thanks to the Orano Group's expertise in the nuclear industry and its access to thorium-232, a scarce raw material required for producing 212Pb, Orano Med is also responsible for the entire production and distribution chain for these isotopes."
The collaboration represents another significant milestone for Orano Med (搜索), following their licensing agreement with Sanofi for their most advanced clinical program, AlphaMedix™, which received FDA Breakthrough Designation in 2024 for GEP-NET tumors (搜索). The company continues to advance several potential treatments using 212Pb combined with various targeting agents through clinical and preclinical studies.