First Patients Dosed With TLX597-Tx in Trial for mHSPC

The first patients have been dosed with TLX597-Tx (177Lu-DOTA-HYNIC-panPSMA) in the phase 2 OPTIMAL-e trial (ACTRN12626000034336), a study evaluating the investigational prostate-specific membrane antigen (PSMA)–targeting radioligand therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to a news release from Telix Pharmaceuticals Limited and St Vincent’s Hospital in Sydney, Australia.¹

OPTIMAL-e is a single-arm, open-label, nonrandomized pilot study led by Louise Emmett, MD, director of theranostics and nuclear medicine at St Vincent’s Hospital. The trial is evaluating adaptive-dosed TLX597-Tx in combination with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) in patients with mHSPC. The primary end point is prostate-specific antigen (PSA) response in this earlier treatment setting, along with assessment of the depth and durability of PSA response and the safety of dose intensification.

Study Design

OPTIMAL-e builds on the earlier OPTIMAL-PSMA study (ACTRN12625000971437), which recently completed patient enrollment. According to Telix, TLX597-Tx has demonstrated a favorable biodistribution and dosimetry profile in prior studies, including OPTIMAL-PSMA, with low exposure to the salivary glands and kidneys, the healthy organs of greatest concern with PSMA-targeted radioligand therapy, alongside high uptake in PSMA-expressing tumors.^1,2

In OPTIMAL-e, patients will receive continuous ARPI and ADT along with adaptive-dosed TLX597-Tx administered intravenously on day 8, day 10, and week 6 after the start of ARPI treatment, with 4 more doses administered every 8 weeks. At week 12, a PSMA PET/CT scan and PSA test will determine whether the fourth dose of the experimental treatment will be given or paused.³ Treatment can also be paused after the fifth dose, but only 1 treatment pause is allowed. An additional 3 doses can be given at the physician’s discretion after the seventh dose. The target PSA of the primary end point is less than 0.2 ng/mL by blood test at 6 months.

Patients must have synchronous or high-volume metachronous mHSPC, be naive to treatment or have minimal prior treatment with no prior ARPI, and have evidence of PSMA-positive disease.

Under the adaptive-dosing approach being tested in OPTIMAL-e, treatment with lutetium-177–based PSMA radioligand therapy is continued only while the PSMA target remains detectable and is paused once a marked reduction in tumor burden is observed, with retreatment initiated at the first confirmed PSA rise once the target has returned.¹ This strategy is intended to maintain disease control while limiting unnecessary treatment exposure, potentially prolonging the time patients remain in a low-volume disease state and supporting quality of life. Treatment decisions in the study are guided by serial PSMA-PET imaging and PSA measurements.

“This individualized strategy aims to maintain disease control while minimizing unnecessary treatment exposure, with the potential to keep patients in a low-volume disease state for longer and support quality of life,” Emmett stated in the news release.

David N. Cade, MD, group chief medical officer at Telix, noted that although the currently approved radioligand therapy for advanced disease has shown a modest overall survival benefit, earlier intervention with TLX597-Tx may offer the potential to further improve outcomes and prolong quality of life.

Broader Development Context

Telix’s antibody-based prostate cancer therapy, TLX591-Tx (lutetium-177 [177Lu] rosopatamab tetraxetan), is currently being evaluated in the phase 3 ProstACT Global trial (NCT06520345) in metastatic castration-resistant prostate cancer and is actively dosing patients in jurisdictions with regulatory approval. Telix noted that TLX591-Tx and TLX597-Tx have complementary mechanisms of action, suggesting the potential for distinct applications across the mCRPC and mHSPC treatment settings.¹

REFERENCES

1. First Patients Dosed in OPTIMAL-e Trial for Earlier Stage Prostate Cancer. News release. Telix. July 15, 2026. Accessed July 16, 2026. https://tinyurl.com/mrysen89

2. OPTIMAL-PSMA Trial of TLX597-Tx Next Generation RLT Presented at IPCS 2026 Highlighting Therapeutic Potential in Prostate Cancer. News release. Telix. April 29, 2026. Accessed July 16, 2026. https://tinyurl.com/mrynjtfb

2. A single arm study of Androgen Receptor Pathway inhibition plus Adaptive-dosed [177Lu]Lu-PSMA-597 in metastatic hormone sensitive prostate cancer (OPTIMAL-e). ANZTCR.org.au. Updated June 16, 2026. Accessed July 16, 2026. https://tinyurl.com/4csbfz6y