External Beam Therapy with Theranostic Radioligand Therapy for Oligometastatic Prostate Cancer (ProstACT TARGET) - Trial in Progress

Introduction: The use of theranostics is becoming increasingly relevant as PSMA-based molecular imaging for patients with biochemically recurrent prostate cancer reveals an increased prevalence of oligometastatic disease, for which a consensus approach to therapy is pending. The challenge for both the patient and the physician at the onset of biochemical recurrence (BCR) is to balance quality of life, morbidity and the cost and efficacy of available options to treat against the risk of disease progression. Currently, external beam radiotherapy (EBRT) is a commonly used first line of treatment in this setting. With the success of molecularly targeted therapy in later disease settings, we propose theranostics may be an appropriate treatment option for this class of patients.

Methods: ProstACT-TARGET (NCT05146973) is a multicentre, prospective, single arm, open-label, Phase 2 trial that aims at assessing the combined effect of targeted radioimmunotherapy ¹⁷⁷Lu-TLX591 (¹⁷⁷Lu-DOTA-huJ591; ¹⁷⁷Lu-DOTA-rosopatamab) in combination with external beam radiotherapy (EBRT) for patients with biochemically recurrent oligometastatic disease. Ten patients will undergo a dosimetry sub-study to monitor safety and tissue radioexposure to ¹⁷⁷Lu-TLX591 when combined with EBRT.

Men aged ≥18 years, with biopsy proven prostate adenocarcinoma with Gleason score 7 or higher at primary presentation, who have previously undergone a radical prostatectomy and have BCR disease (serum PSA > 0.2 ng/dL confirmed) and PSMA avid pelvic nodal disease (<5 lesions), and who are eligible for treatment with EBRT are invited to participate. Patients must not have had prior EBRT or androgen deprivation therapy (ADT) within 12 months of trial screening. After successful screening and eligibility confirmation, patients are enrolled and will commence EBRT over the standard 6-7.5 weeks. Four weeks after completion of EBRT, two doses of ¹⁷⁷Lu-TLX591 will be administered, 14 days apart, intravenously. Participants will then be followed every 3 months for up to a year.

The primary endpoint is PSA progression free survival. Secondary endpoints include overall survival, objective tumor response rate, radiographic progression free survival, sites of tumor progression, health related quality of life outcomes, time to distant metastasis, time to commencement of ADT, as well as safety and tolerability assessed as per NCI-CTCAE 5.0.

This trial is open to accrual with one patient enrolled. Changes to study plans will now allow patients to undergo standard EBRT therapy at treatment facilities that may be closer to their home and receive ¹⁷⁷Lu-TLX591 treatment at four designated study centers. All primary and secondary outcomes data will be collected for all participants, and intention to treat principles will be used for outcome analysis. Baseline factors across groups will be compared using mean (standard deviation) and median (25^th and 75^th percentiles) summary measures.

ClinicalTrials.gov Identifier: NCT05146973

Acknowledgements / Disclosures: Stefanie D. Martina and Ryan Dorton, Telix Pharmaceuticals, provided editorial support. This study is cosponsored by Telix Pharmaceuticals and Genesis Care.

Results: Not applicable.

Conclusions: Not applicable.