Concepts in Phase 1 Radiopharmaceutical Therapy Trial Designs: Lessons from the SNMMI Dose Optimization in Radiopharmaceutical Therapy Development Workshop

Radiopharmaceuticals represent a promising new frontier in cancer therapy. In the United States, cancer is the second leading cause of death. There is an urgent need to develop new therapies to meet this challenge, especially for those patients with advanced and refractory disease. The Society of Nuclear Medicine and Molecular Imaging and Food and Drug Administration convened a "Dose Optimization of Radiopharmaceutical Therapy Developmental Workshop" on May 6 and 7, 2024. Herein, we briefly summarize the highlights from that meeting from the perspective of the stakeholders involved, including multiple representatives from academia, industry, and the Food and Drug Administration. For patients with advanced treatment-refractory solid tumors, the greatest health-related risk is their cancer, rather than long-term toxicity from radiopharmaceutical therapies. In these patients, concerns about long-term nephrotoxicity, marrow toxicity, or the development of second malignancies are of lesser importance given that there is little or no long-term probability of survival. Phase 1 studies that explore dose and schedule are crucial because they set the stage for larger studies that potentially inform regulatory approval.