The single-center, single-arm phase 1/2 AlphaBet trial will evaluate the combination of radium-223 (223Ra) and [lutetium-177 (177Lu)]Lu-prostate-specific membrane antigen (PSMA)-I&T in patients with metastatic castration-resistant prostate cancer (mCRPC).
[177Lu]Lu-PSMA is often used as a radioligand therapy for the treatment of mCRPC, yet the responses for many patients who receive it are not durable, and some patients eventually develop progressive disease. Bone marrow is the most common site of progression, and metastases in this area are unlikely to receive an adequate dose of radiation. 223Ra can be combined with [177Lu]Lu-PSMA to improve the eradication of metastatic disease in areas such as bone marrow.
The trial will include 36 patients with prostate cancer who will receive [177Lu]Lu-PSMA-I&T 7.4 GBq in combination with 223Ra in escalating doses (28 kBq/kg-55kBq/kg). Both will be administered intravenously every 6 weeks for up to 6 cycles.
Patients must have at least 2 untreated bone metastases visible on bone scintigraphy and PSMA-positive disease on PSMA positron emission tomography (PET) scan. They also must have adequate bone marrow and organ function and be willing to undergo tumor biopsies.
Patients with discordant disease visible on 18F-fludeoxyglucose (FDG) PET scan (defined as FDG-positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than 1 prior line of chemotherapy for prostate cancer.
Researchers began enrolling patients in the AlphaBet trial in the third quarter of 2022, and recruitment is anticipated to continue for 24 months.