ProstACT GLOBAL Results May Support “Open” Decisions in Metastatic CRPC

If the outcomes of the phase 3 ProstACT GLOBAL study (NCT04876651) are positive, they may support an “open” decision on administering lutetium Lu 177 (¹⁷⁷Lu) rosopatamab (TLX591) alone or in combination with other therapies for patients with metastatic castration-resistant prostate cancer (CRPC), according to Scott T. Tagawa, MD, MS, FASCO, FACP.

At the American Urological Association 2025 Annual Meeting,Tagawa spoke with CancerNetwork^® about his clinical trial in progress presentation on the ProstACT GLOBAL study assessing ¹⁷⁷Lu rosopatamab plus standard of care vs standard of care alone among those with metastatic CRPC.¹

According to Tagawa, it is unclear whether future work would support this agent being implemented in clinical practice as a monotherapy or as part of a combination regimen. Based on prior studies such as the phase 3 VISION trial (NCT03511664), in which a portion of patients received androgen receptor pathway inhibitors (ARPIs) in combination with radiopharmaceutical therapy, combinatorial strategies may help with achieving outcomes such as upregulating prostate-specific membrane antigen (PSMA).

Tagawa is a professor of medicine and urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian/Weill Cornell Medical Center.

Transcript:

If this study [outcome] is positive, it’s unclear to me what the label would be. It’s very much akin to [phase 3] ALSYMPCA [NCT00699751] and then the [phase 3] VISION [trial. We have] this [study] where there’s a standard of care, limited dealer’s choice, with or without investigational agents. That’s standard. If I’m practicing evidence-based medicine with radium and add something like a hormone agent—in VISION, more than half [of patients received] an androgen receptor pathway inhibitor; it was designed as a combination study—in practice and by label, they are single agents.² It is unclear to me what would happen in practice, but because [ProstACT GLOBAL is] built in as a combination study, if I as a physician wanted to either give an ARPI because I thought there may be some efficacy there or maybe, more importantly, to upregulate PSMA and radiosensitize or combine [it] with docetaxel—although that’s sequential, so I think the radiosensitizing parts are going to be lost sequentially—[that is] hitting 2 different compartments. If there is heterogeneity and some PSMA-negative or low-expressing cells, I’ll also be able to target that with the chemotherapy.

If [the study outcome is] positive, I think it would be a relatively open [decision], and we would choose, as physicians, whether to give [¹⁷⁷Lu rosopatamab] in combination or as a single agent.

References

1. Tagawa S, Agarwal N, Cade D, Sartor O. ProstACT GLOBAL: a phase 3 study of 177Lu-rosopatamab plus standard of care vs. standard of care alone in patients with metastatic castration-resistant prostate cancer. Presented at: American Urological Association 2025 Annual Meeting; April 26-29, 2025; Las Vegas, NV.
2. Sartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322