Dr Tagawa on the Evaluation of Lutetium Lu 177 Rospatamab Tetraxetan Plus SOC in mCRPC

"[The trial is evaluating] lutetium Lu 177 rosopatamab tetraxetan with standard of care vs standard of care alone with a primary endpoint of radiographic progression-free survival. A key secondary end point that has been powered [is] OS, and there's some interesting OS data based on the prior phase 1/2 studies."

Scott T. Tagawa, MD, FASCO, FACP, MS, a professor of medicine and urology at Weill Cornell Medicine and attending physician at NewYork-Presbyterian Hospital, discussed the rationale behind the ongoing, phase 3 ProstACT GLOBAL trial (NCT06520345), which is evaluating the addition of lutetium Lu 177 rosopatamab tetraxetan to standard of care (SOC) vs SOC alone in patients with metastatic castration-resistant prostate cancer (mCRPC)

The ProstACT GLOBAL trial is enrolling patients with prostate-specific membrane antigen (PSMA)–positive mCRPC who have experienced disease progression following treatment with a second-generation androgen receptor pathway inhibitor (ARPI). Patients may have received prior docetaxel in the metastatic hormone-sensitive setting if the last dose was given at least 6 months before screening. Following a safety lead-in portion of the study, eligible patients are being randomly assigned 2:1 to receive lutetium Lu 177 rosopatamab tetraxetan plus SOC or SOC alone. SOC, which is determined by the investigator prior to randomization, includes docetaxel plus an ARPI switch to abiraterone acetage (Zytiga) or enzalutamide (Xtandi).

Unlike prior trials evaluating PSMA-targeted therapies, ProstACT GLOBAL incorporates docetaxel as the SOC option, reflecting broader real-world practice, Tagawa said. According to Tagawa, this design allows the study to evaluate the efficacy of the radioligand therapy across different treatment backbones, including sequential or concurrent use with chemotherapy.

The primary end point of the trial is radiographic progression-free survival (rPFS); overall survival (OS) is a key secondary end point for which the study is powered. Additional end points include objective response rate (ORR), symptomatic skeletal event rate, prostate-specific antigen response, and health-related quality of life. Tagawa explained that the data derived regarding OS could build on prior phase 1/2 data for the agent, highlighting a potential survival benefit with lutetium Lu 177 rosopatamab tetraxetan.