Published data support PSMA-PET–guided selection for 177Lu-rosopatamab tetraxetan in mCRPC

Results from the phase 1 ProstACT SELECT trial (NCT04786847) have been published in the journal Cancers, suggesting that ⁶⁸Ga-PSMA-11 PET imaging can identify patients with metastatic castration-resistant prostate cancer (mCRPC) who are suitable for treatment with the investigational radio antibody-drug conjugate (rADC) lutetium-177 (¹⁷⁷Lu) rosopatamab tetraxetan (TLX591-Tx).¹

The findings demonstrated concordance between tumor targeting with SPECT/CT imaging and uptake on PSMA-PET imaging, supporting utility of ⁶⁸Ga-PSMA-11 PET for patient selection. The results also provided early evidence of a manageable safety profile and prolonged tumor retention of ¹⁷⁷Lu-rosopatamab tetraxetan when administered with standard of care (SOC) in patients with mCRPC.

How was the ProstACT SELECT trial designed?

ProstACT SELECT (NCT04786847) was a multicenter, open-label, single-arm phase 1 study that enrolled 30 patients with PSMA-expressing mCRPC who had experienced disease progression despite prior androgen receptor pathway inhibitor (ARPI) therapy. Patients received intravenous ¹⁷⁷Lu-rosopatamab tetraxetan alongside investigator-determined SOC. Cohort 1 received an imaging dose of ¹⁷⁷Lu-rosopatamab tetraxetan (1 GBq [27 mCi]), followed 14 days later by 1 therapeutic dose (2.8 GBq [76 mCi]). Cohort 2 received 2 therapeutic doses of ¹⁷⁷Lu-rosopatamab tetraxetan 14 days apart.

The key objectives of the study were to evaluate safety, tolerability, biodistribution, and radiation dosimetry, as well as preliminary efficacy by radiographic progression-free survival (rPFS).

Participants underwent baseline ⁶⁸Ga-PSMA-11 PET imaging to confirm eligibility. Investigators then compared these scans qualitatively with serial SPECT/CT imaging performed after administration of ¹⁷⁷Lu-rosopatamab tetraxetan. According to the published analysis, tumor targeting observed on SPECT/CT closely corresponded with baseline PET findings, supporting the use of PSMA-PET as a companion imaging approach for patient selection.

Dosimetry analyses in cohort 2 demonstrated the highest absorbed radiation dose in the liver, the primary clearance organ (2.44 ± 0.56 Gy/GBq), with comparatively lower radiation exposure to the kidneys (0.64 ± 0.17 Gy/GBq) and salivary glands (0.07 ± 0.03 Gy/GBq).

According to the authors, “The mean absorbed dose for all tumors was 0.76 ± 0.57 Gy/GBq, with absorbed doses in bone, visceral and nodal lesions of 0.98 ± 0.59, 0.84 ± 0.81 and 0.36 ± 0.16 Gy/GBq, respectively.” Investigators also reported persistent tumor retention through the final protocol-specified imaging assessment at 312 hours following administration.

No new safety signals were identified during the study. There were 212 treatment-emergent adverse events reported among 30 patients, of which 125 (59%) were considered related to treatment.

Among the 16 patients included in the efficacy analysis, the median rPFS was 8.8 months (95% CI, 4.0 to 11.3). One patient (6.3%) achieved a partial response, and 13 (81.3%) demonstrated stable disease.

"A key objective of ProstACT SELECT was to determine whether PSMA-PET imaging could reliably identify patients suitable for TLX591-Tx therapy, and the results clearly support this approach,” said principal investigator Nat Lenzo, MD, a nuclear medicine oncologist, in a news release on the findings.² “The results provide compelling evidence that the PSMA-PET imaging agent and TLX591-Tx are targeting the same disease sites, supporting the ongoing ProstACT Global trial for mCRPC, where there remains significant unmet need for additional treatment options."

The ongoing ProstACT Global trial (NCT06520345) is evaluating ¹⁷⁷Lu-rosopatamab tetraxetan plus SOC vs SOC alone in approximately 490 patients with PSMA-positive mCRPC who have progressed following 1 prior ARPI. Part 1 of the study previously demonstrated acceptable safety and dosimetry findings, allowing progression to the randomized expansion phase.³

REFERENCES
1. Lenzo N, O’Byrne K, Ngai S, Krieger L, Wong V, Cade DN. Theranostic Potential of 177Lu-TLX591 with Best Standard-of-Care and 68Ga-PSMA-11 PET for Patients with Metastatic Castration-Resistant Prostate Cancer: Results from the Phase 1 ProstACT SELECT Trial. Cancers. 2026; 18(14):2331. doi:10.3390/cancers18142331

2. TLX591-Tx ProstACT SELECT study published in Cancers Journal. News release. Telix Pharmaceuticals. July 21, 2026. Accessed July 22, 2026. https://telixpharma.com/news-views/tlx591-tx-prostact-select-study-published-in-cancers-journal/ 

3. ProstACT Global phase 3 study (part 1) achieves primary objectives. News release. Telix Pharmaceuticals. March 9, 2026. Accessed March 12, 2026. https://telixpharma.com/news-views/prostact-global-phase-3-study-part-1-achieves-primary-objectives/