Boston, Massachusetts, U.S., and Vancouver, British Columbia, Canada, September 8, 2026
Alpha-9 Oncology has announced the dosing of the first patient in a Phase 1 clinical trial evaluating two investigational GRPR-targeted radiotherapeutics across advanced and metastatic solid tumors. The study is evaluating 225Ac-A9-0642, an alpha-emitting actinium-based radiotherapeutic, and 177Lu-A9-0631, a beta-emitting lutetium-based compound, both designed to target the gastrin-releasing peptide receptor (GRPR). The clinical program represents a significant development milestone for Alpha-9’s targeted radiotherapeutic pipeline and will assess safety, tolerability, dosimetry and recommended doses for further clinical development. Initial clinical data are expected in late 2027.
Alpha-9 Advances Dual GRPR Radiotherapeutic Program
The Phase 1 trial is designed to evaluate 225Ac-A9-0642 and 177Lu-A9-0631 in patients with GRPR-positive advanced or metastatic tumors. GRPR is a receptor expressed across several solid tumors, including breast cancer, making it a potential target for precision radiopharmaceutical development. Alpha-9 is developing the two compounds in parallel to investigate different radioactive payload approaches while generating clinical evidence for its broader molecular engineering platform. The company describes 225Ac-A9-0642 as the first actinium-based GRPR-targeting compound to enter clinical evaluation. Alpha-9 is investigating the alpha-emitting radiotherapeutic for its potential to provide enhanced antitumor activity compared with earlier-generation lutetium-based approaches. In parallel, 177Lu-A9-0631 is being developed as a lutetium-based GRPR-targeted radiotherapeutic with the potential for differentiated clinical performance. The dual-program strategy allows investigators to evaluate alpha- and beta-emitting radionuclides against the same biological target while examining how differences in radiation characteristics may influence therapeutic development. However, the compounds remain investigational, and their clinical efficacy and safety will need to be established through prospective clinical studies.
Phase 1 Study to Assess Safety and Dosimetry
The newly initiated Phase 1 study will focus primarily on safety, tolerability, dosimetry and dose optimization. The trial is also intended to determine the recommended dose for expansion, providing the foundation for subsequent studies in selected tumor populations. Patients enrolled in the program will have tumors confirmed to express GRPR. A key component of the development strategy is the use of Alpha-9’s proprietary 68Ga-A9-6217 imaging compound for patient selection. Diagnostic imaging is intended to identify patients whose tumors can be effectively targeted through GRPR expression, supporting a precision-medicine approach to radiotherapeutic treatment. According to Alpha-9, imaging data generated with 68Ga-A9-6217 demonstrated tumor targeting with limited uptake in healthy organs. These characteristics could be important for targeted radiopharmaceutical development because the therapeutic objective is to deliver radiation preferentially to tumor tissue while minimizing exposure to normal organs. The company also reported that early compassionate-use experience with 177Lu-A9-0631 showed the compound was well tolerated in individuals with GRPR-positive tumors. These observations are preliminary and are separate from the formal evidence that will be generated through the Phase 1 clinical trial.
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Modular Platform Supports Radiopharmaceutical Development
Beyond the individual compounds, the program highlights Alpha-9’s modular radiotherapeutic engineering platform, which is designed to optimize multiple components of a radiopharmaceutical, including the target-binding molecule, linker, chelator and radioactive isotope. The company aims to create fit-for-purpose combinations tailored to specific targets and indications. For clinical development, this approach could enable systematic optimization of tumor retention and healthy-tissue exposure, two important considerations in radiopharmaceutical development. The parallel evaluation of actinium-225 and lutetium-177 also provides an opportunity to generate comparative development data across different radiation modalities. The first-patient dose marks the transition of both GRPR programs into clinical testing. With data expected in late 2027, the Phase 1 study will provide important information on the safety profile, biodistribution, radiation dosimetry and appropriate dosing strategy for subsequent development. If the investigational compounds demonstrate acceptable safety and evidence of tumor targeting, the program could advance toward expansion studies in GRPR-positive solid tumors, including breast cancer and other cancers with significant unmet medical need.
Source: Alpha-9 Oncology press release
