Study to assess adaptive-dosed 177Lu-DOTA-HYNIC-panPSMA in mHSPC

The first patients have been dosed in the phase 2 OPTIMAL-e study evaluating the investigational prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) lutetium-177 (¹⁷⁷Lu) DOTA-HYNIC-panPSMA (TLX597-Tx) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), marking the expansion of the agent into an earlier disease setting.¹

The study, led by Louise Emmett, MD, MBChB, FRACP, FAANMS, at St. Vincent's Hospital Sydney, is designed to evaluate whether response-adapted administration of ¹⁷⁷Lu-DOTA-HYNIC-panPSMA in combination with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) can deepen prostate-specific antigen (PSA) responses while limiting unnecessary treatment exposure through an adaptive dosing strategy.

“I am excited to lead the OPTIMAL-e trial, which is evaluating an adaptive treatment approach designed to tailor therapy to each patient's response,” Emmett said in a news release.¹ “By using PSMA-PET imaging and PSA measurements to monitor disease burden, treatment can be continued when the PSMA target persists and paused when there is a significant reduction in tumor burden. 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.”

Design of the OPTIMAL-e trial

OPTIMAL-e is a phase 2, single-arm, open-label, nonrandomized pilot study enrolling men with mHSPC. Patients will receive adaptive-dosed ¹⁷⁷Lu-DOTA-HYNIC-panPSMA in combination with standard ADT and an ARPI. According to the study description, treatment decisions will be guided by serial PSMA-PET imaging and PSA measurements. Therapy may be paused when a substantial reduction in PSMA-expressing disease burden is observed and resumed following confirmed PSA rise and the return of the imaging target.

The primary objective is to evaluate PSA response rates while also assessing the depth and durability of response and the safety of dose intensification. Investigators also aim to determine whether response-adapted treatment can maintain disease control while reducing cumulative treatment exposure.

Emmett also noted, “The findings from OPTIMAL-e may help shape future treatment strategies and advance precision medicine for men living with prostate cancer.”

Building on earlier ¹⁷⁷Lu-PSMA development

¹⁷⁷Lu-DOTA-HYNIC-panPSMA is an investigational small-molecule PSMA-targeted radioligand therapy. The compound is being developed alongside the company's antibody-based investigational radiopharmaceutical ¹⁷⁷Lu-rosopatamab tetraxetan (TLX591-Tx), which is currently being evaluated in the phase 3 ProstACT Global trial (NCT06520345) in patients with mCRPC. Both agents remain investigational and have not received regulatory approval in any jurisdiction.

The initiation of OPTIMAL-e follows early dosimetry results from the phase 2 OPTIMAL-PSMA study, which evaluated ¹⁷⁷Lu-DOTA-HYNIC-panPSMA in metastatic castration-resistant prostate cancer (mCRPC). Preliminary dosimetry findings presented earlier this year suggested higher activity per cycle with the dose-intensification regimen, while also maximizing the radiation dose to cancerous lesions.² These findings provided the rationale for exploring dose intensification and evaluation in earlier-stage disease.

REFERENCES
1. First patients dosed in OPTIMAL-e trial for earlier stage prostate cancer. News release. Telix Pharmaceuticals. July 15, 2026. Accessed July 16, 2026. https://www.globenewswire.com/news-release/2026/07/15/3328129/0/en/first-patients-dosed-in-optimal-e-trial-for-earlier-stage-prostate-cancer.html

2. OPTIMAL-PSMA trial of TLX597-Tx next generation RLT presented at IPCS 2026 highlighting therapeutic potential in prostate cancer. News release. Telix Pharmaceuticals. April 30, 2026. Accessed July 16, 2026. https://telixpharma.com/news-views/optimal-psma-trial-of-tlx597-tx-next-generation-rlt-presented-at-ipcs-2026-highlighting-therapeutic-potential-in-prostate-cancer/