A first-in-human trial of SNA028, a two-step pretargeted radioimmunotherapy targeting the GPA33 antigen, has been registered at Tianjin Medical University Cancer Institute and Hospital in China, in a trial sponsored by China-based firm SmartNuclide Biopharma. The move marks the clinical debut of a radiopharmaceutical approach to GPA33-positive advanced colorectal cancer. The SNA028 clinical trial (NCT07590856) is listed as not yet recruiting, with a planned start date of May 2026 and primary completion expected by December 2027.
The Phase I study is single-center, open-label, and non-randomized, enrolling up to 20 adults aged 18 to 75 with histopathologically confirmed colorectal cancer who have progressed on standard therapy and carry GPA33-positive tumors with at least one measurable lesion per RECIST 1.1. The sequential seven-arm design reflects the three optimization questions the trial is structured to answer: the appropriate dose of GPA33-CC, the interval between GPA33-CC and 177Lu-SmartD2 administration, and the mass dose of the radiolabeled effector. GPA33-CC is tested at 0.3, 1, and 3 mg/kg; intervals between the two components are set at 3, 5, or 7 days; and SmartD2 mass doses range from 60 to 200 nmol, according to the trial record. Primary endpoints cover safety and tolerability, pharmacokinetics of GPA33-CC, and radiation dosimetry of 177Lu-SmartD2, with secondary endpoints assessing biodistribution via standardized uptake values and immunogenicity of the targeting component.
GPA33 targeting in colorectal cancer
GPA33, or Glycoprotein A33, is a cell-surface antigen expressed broadly and selectively across primary and metastatic colorectal cancer, including in putative cancer stem cell populations, making it a durable target for antibody-based approaches in this disease. The pretargeted radioimmunotherapy architecture of SNA028 is designed to decouple tumor localization from radionuclide delivery: GPA33-CC is administered first to accumulate at GPA33-positive tumor tissue, and after a defined clearance interval, 177Lu-SmartD2 is infused to bind the pre-localized targeting agent and deliver beta-particle irradiation selectively to the tumor site.
Lutetium-177 is a beta-emitting radionuclide whose relatively short path length is suited to irradiating small tumor deposits while limiting exposure to surrounding normal tissue, a property that has driven its adoption across published preclinical GPA33-targeted PRIT systems.