A new alpha-emitting radiopharmaceutical therapy for advanced prostate cancer has shown promising results in a phase 1 trial. The treatment, known as 212Pb-ADVC001, was well tolerated and demonstrated strong antitumor activity, with 80 percent of patients experiencing a decline in prostate-specific antigen (PSA) levels of at least 50 percent.
The findings support further clinical development of 212Pb-ADVC001 to address the significant unmet needs in metastatic androgen pathway modulation-resistant (mAPM-R) prostate cancer.
Treatment Approach
Prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy is an established treatment for mAPM-R prostate cancer. However, approximately one-third of patients are resistant to the commonly used beta-emitting treatment, 177Lu-PSMA-617.
Alpha-emitting radiopharmaceutical therapies, such as 212Pb-ADVC001, have emerged as a new treatment approach. Unlike beta emitters, alpha emitters release high-energy particles that travel only a few cell widths, delivering concentrated radiation to cancer cells while sparing surrounding healthy tissue.
Clinical Trial Results
The TheraPb phase 1 trial evaluated the safety and efficacy of 212Pb-ADVC001 in 22 patients with progressive mAPM-R prostate cancer. The study found no dose-limiting toxicities, and the most common treatment-related adverse events were dry mouth and nausea.
The maximum tolerated dose was not reached, and the study committee selected 160 and 200 MBq as the recommended doses for phase 2 of TheraPb. The median radiographic progression-free survival was 11.2 months, and the overall response rate was 100 percent.
According to the study authors, “Flexibility in dosing, together with the overall safety profile of 212Pb-ADVC001, further provides a rationale for evaluating combination strategies with other anti-cancer agents to maximize clinical outcomes.”
Future Development
The study authors note that current radiopharmaceutical therapies use fixed dosing regimens that do not account for variability in tumor response, highlighting the need for novel treatment strategies that may enhance patient outcomes using more potent payloads and optimization of dose and schedule.