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

Commentary
Video

Findings from prior studies, such as the phase 3 VISION trial, may support the notion of combining radiopharmaceuticals with best supportive care.

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
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