(UroToday.com) The 2025 ESMO annual meeting featured a prostate cancer session and a presentation by Dr. Louise K. Kostos discussing the first results of the AlphaBet trial, a phase I/II trial of combined radium-223 and 177Lu-PSMA-I&T in patients with metastatic castration resistant prostate cancer (mCRPC). 177Lu-PSMA-I&T and Radium-223 are approved life-prolonging therapies for mCRPC. However, resistance and progression, particularly in bone, are common. Radium-223, a bone-seeking alpha emitter, has a shorter path length and higher linear energy transfer than beta emitters such as 177Lu, and may be suited for targeting micrometastatic osseous disease. The AlphaBet trial evaluated 177Lu-PSMA-I&T in combination with radium-223, a bone-seeking alpha emitter, in patients with mCRPC.
This was a single-center, single-arm, investigator-initiated phase I/II trial at the Peter MacCallum Cancer Centre. The key eligibility criteria included progressive mCRPC with ≥2 untreated bone metastases, PSMA-PET positive disease (SUVmax ≥ 20) with no discordance (FDG-positive with minimal PSMA and bone scan uptake), and prior exposure to ≥1 androgen receptor pathway inhibitor. Patients received radium-223 and 7.4 GBq 177Lu-PSMA-I&T IV 6-weekly, for up to 6 cycles. Two dose levels of radium-223 (27.5 and 55 KBq/kg) were evaluated:
The co-primary endpoints were determining the maximum tolerated dose, recommended phase II dose, and PSA response rates. Key secondary endpoints included safety, PSA progression free survival, and radiographic progression free survival.
Between November 3, 2022, and November 5, 2024, 36 patients were enrolled. The median age was 72.5 years (IQR 67.0-78.0), median baseline PSA was 22 ng/mL (IQR 5.8-113.0), and median ALP was 111.5 U/L (IQR 81.5-157.2). Overall, 19 patients (53%) received prior docetaxel, and no dose-limiting toxicities were observed. The maximum tolerated dose and recommended phase II dose was 55 KBq/kg radium-223 with 7.4 GBq 177Lu-PSMA-I&T. There were 11 patients (31%) that received 6 cycles of both radium-223 and 177Lu-PSMA-I&T. Grade ≥3 treatment-related adverse events occurred in 14% of patients and included anemia (n = 4) and neutropenia (n = 3) (non-clinically significant lymphopenia, n = 10); there were 4 patients (11%) that experienced grade 2 thrombocytopenia. No fractures or treatment-related deaths occurred.
PSA50 and PSA90 response rates were 55% (95% CI 36–72) and 18% (7–35), respectively. Over a median follow-up of 13.3 months, the median PSA progression free survival was 5.3 months (95% CI 4.0–9.0), and median radiographic progression free survival was 10.0 (95% CI 6.7–13.5):
Dr. Kostos concluded this presentation discussing the first results of the AlphaBet trial with the following take home points:
- The combination of 177Lu-PSMA-I&T and radium-223 is safe and well-tolerated, demonstrating antitumor activity in patients with progressive mCRPC and bone metastases
- The findings support further evaluation of combined alpha/beta-emitting approaches
Presented by: Louise K. Kostos, MBBS, Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 European Society of Medical Oncology (ESMO) Annual Congress held in Berlin, Germany, between September 17th and 21st.