Late-breaking data from Telix Pharmaceuticals’ ongoing Phase 3 ProstACT Global study, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 – June 2, 2026, in Chicago, Illinois, provides compelling evidence for the safety and feasibility of TLX591-Tx (lutetium-177 [177Lu] rosopatamab tetraxetan) in combination with standard-of-care (SoC) therapies in patients with metastatic castration-resistant prostate cancer (mCRPC). These results support further clinical development of this novel PSMA-targeted radio antibody-drug conjugate (rADC) as a potential new treatment option.
Metastatic castration-resistant prostate cancer (mCRPC) remains a challenging clinical entity, with patients often progressing despite contemporary therapies such as abiraterone, enzalutamide, and taxanes. There is an ongoing need for new treatment modalities that can be effectively combined with existing standards of care without compromising safety or efficacy. TLX591-Tx, a first-in-class PSMA-targeted lutetium rADC, is being investigated to address this unmet need by leveraging targeted radiopharmaceutical therapy in combination with established systemic treatments.
Study design
ProstACT Global (ClinicalTrials.gov ID: NCT06520345) is an international, multicenter, randomized Phase 3 trial designed to reflect real-world clinical practice. Eligible participants had PSMA-positive mCRPC confirmed on 68Ga-PSMA-11 PET imaging and prior exposure to one androgen receptor pathway inhibitor (ARPI). Part 1 of the study evaluated safety, dosimetry, and pharmacokinetics of TLX591-Tx administered as two intravenous doses (76 mCi each, 14 days apart) in combination with standard-of-care: Cohort 1, abiraterone (Zytiga®; Janssen Biotech), (n=11), Cohort 2, enzalutamide (Xtandi®; Astellas Pharma US, and Pfizer), (n=11), and Cohort 3 (TLX591-Tx followed by docetaxel (Taxotere®; Sanofi), (n=14). Patients were monitored for treatment-emergent adverse events (TEAEs) and underwent serial SPECT/CT imaging for dosimetry and blood sampling for pharmacokinetics. [1]
Results
A total of 36 patients (median baseline PSA: 18.18 ng/mL) received study treatment. All patients received both doses of TLX591-Tx per protocol. Most had high-risk disease (55.6% with Gleason score 8–10; 72% second-line mCRPC; 25% prior taxane exposure).
Safety and Tolerability
TLX591-Tx demonstrated acceptable tolerability across all SoC combination cohorts, with no new safety signals identified. The majority of non-hematologic TEAEs were Grade 1–2, with fatigue (53%), nausea (28%), and dry mouth (25%) being the most common. Hematologic events—including thrombocytopenia (Grade 3: 14%, Grade 4: 31%) and neutropenia (Grade 3: 22%, Grade 4: 25%)—were transient and consistent with expectations for this disease context and therapeutic class. No Grade 5 treatment-related adverse events were reported, and all hematologic events were manageable with standard supportive care.
Dosimetry and Pharmacokinetics
Radiation exposure to key organs remained well below established safety thresholds. [2] The liver received the highest absorbed dose (1.62–5.08 mGy/MBq), followed by the kidneys (0.336–0.961 mGy/MBq), with minimal uptake in the salivary glands (0.001–0.104 mGy/MBq). Serial imaging confirmed sustained radioconjugate retention in the tumor through Day 15, with all cohorts demonstrating favorable lesion dosimetry. Pharmacokinetic analyses revealed predictable, bi-exponential blood clearance and no evidence of drug-drug interactions impacting TLX591-Tx targeting, distribution, or elimination.
Robust support
These data provide robust support for the feasibility of combining TLX591-Tx with current SoC therapies in mCRPC. Importantly, the safety profile was consistent with prior studies, and adverse events were generally manageable and predictable. [3] Notably, unlike some small-molecule PSMA radioligand therapies, TLX591-Tx exhibited minimal renal or salivary gland uptake, potentially reducing the risk of nephrotoxicity and xerostomia. [4][5] The agent’s hepatic clearance pathway may further mitigate the risk of renal toxicity, as the liver is relatively radioresistant compared with other organs. [6] The absence of significant drug-drug interactions and the maintenance of radiation doses within safe limits support continued development and integration of this modality in multi-agent regimens for advanced prostate cancer.
What’s next
Part 1 of the ProstACT Global study demonstrates that TLX591-Tx, in combination with standard-of-care therapies, is well tolerated and delivers favorable dosimetry in patients with mCRPC. The findings support ongoing investigation in the randomized expansion phase (Part 2), with the potential to establish TLX591-Tx as a new therapeutic option in this setting.
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Clinical trials
The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global) – ClinicalTrials.gov ID NCT06520345
Highlights of Prescribing Information
Abiraterone (Zytiga®; Janssen Biotech)[Prescribing Information]
Enzalutamide (Xtandi®; Astellas Pharma US, and Pfizer)[Prescribing Information]
Docetaxel (Taxotere®; Sanofi)[Prescribing Information]
References
[1] Barata P, Tincknell G, Gill DM, Fu SY, Singh A, Sartor AO, Cade D, Agarwal N. Safety and dosimetry of 177Lu-rosopatamab tetraxetan plus standard of care in patients with metastatic castration-resistant prostate cancer: Preliminary results from part 1 of phase 3 ProstACT Global study. J Clin Oncol. 2026;44(suppl 17):abstract LBA5009. Presented at: ASCO Clinical Science Symposium; 2026.
[2] The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103, 2007. ICRP Publication 103. Online. last accessed on June 1, 2026
[3] Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, Gupta P, Hartenbach M, Hope TA, Okamoto S, Pfob CH, Pöppel TD, Rischpler C, Schwarzenböck S, Stebner V, Unterrainer M, Zacho HD, Maurer T, Gratzke C, Crispin A, Czernin J, Herrmann K, Eiber M. 68Ga-PSMA-11 PET/CT Interobserver Agreement for Prostate Cancer Assessments: An International Multicenter Prospective Study. J Nucl Med. 2017 Oct;58(10):1617-1623. doi: 10.2967/jnumed.117.190827. Epub 2017 Apr 13. PMID: 28408531.
[4] Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. doi: 10.1016/S1470-2045(23)00529-6. Epub 2023 Nov 30. PMID: 38043558.
[5] Herrmann K, Kratochwil C, Fendler WP, Eiber M, Hustinx R. 2021: the year [177Lu]Lu-PSMA-617 RLT PSMA is ready for incorporation into clinical guidelines? : Reply to “A perspective on the EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands” by Dr. Germo Gericke. Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2668-2669. doi: 10.1007/s00259-021-05409-w. PMID: 34021392; PMCID: PMC8263423.
[6] Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schäfers M, Essler M, Baum RP, Kulkarni HR, Schmidt M, Drzezga A, Bartenstein P, Pfestroff A, Luster M, Lützen U, Marx M, Prasad V, Brenner W, Heinzel A, Mottaghy FM, Ruf J, Meyer PT, Heuschkel M, Eveslage M, Bögemann M, Fendler WP, Krause BJ. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med. 2017 Jan;58(1):85-90. doi: 10.2967/jnumed.116.183194. Epub 2016 Oct 20. PMID: 27765862.
This article is also published in ADC Review | J. Antibody-drug Conjugates (June 1, 2026)
Featured image courtesy © 2020 – 2026 ASCO/Todd Buchanan
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