The first-in-class radio-antibody drug conjugate TLX591 (Lutetium [¹⁷⁷Lu] rosopatamab tetraxetan) showed promising efficacy and safety in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), according to initial results from the phase 1 ProstACT SELECT study (NCT04786847).¹

Treatment with TLX591 resulted in a PSA reduction in nearly two-thirds (64%) of evaluable patients. Twenty-seven percent of patients had a 30% reduction in PSA, and 18% had a 50% reduction.

"Preliminary results from the ProstACT SELECT study build on prior studies of TLX591 and underline the potential advantages of an antibody-based approach. Latest data provides further evidence of the long retention and internalization of TLX591 in the tumor (and metastases), which may maximize the cell-killing effect of the ¹⁷⁷Lu radioisotope at the site of the tumor," Scott T. Tagawa, MD, professor of Medicine and Urology, Weill Cornell Medicine, stated in a news release.1

“TLX591 is a monoclonal antibody (HuX591) conjugated with a DOTA chelator and radiolabelled with ¹⁷⁷Lu (¹⁷⁷Lu-TLX591),” according to the ProstACTSelect trial site on ClinicalTrials.gov.²

The study enrolled 30 patients with PSMA-expressing mCRPC. The efficacy population included 28 of these patients. TLX591 was given in 2 single IV infusions administered 14 days apart. Investigators are continuing to monitor patients for PSA responses as well as radiographic progression-free survival.

Regarding safety, 25% of patients had grade 3 thrombocytopenia and 25% had grade 4 thrombocytopenia. Grade 3 neutropenia occurred in 38% of patients, with grade 4 experienced by 4%. The investigators reported that hematologic events were short-term and reversible. Treatment-related adverse events that were nonhematologic were grade 1/2 and were mostly mild.

"It is really exciting to see development of this next-generation PSMA-targeting radiotherapeutic progressing. This study confirms the suitability of the short, simple treatment duration with two doses administered two weeks apart which is attractive to physicians and patients. The safety and tolerability data also demonstrates the potential for this therapy to reduce undesirable side effects, while delivering a hematologic toxicity profile that is both tolerable and manageable," Nat Lenzo, MD, clinical director theranostics, GenesisCare Group, the top recruiter for the ProstACT SELECT study stated in the news release.¹

Regarding next steps, the phase III ProstACT global study (NCT04876651) is comparing TLX591 plus standard of care with standard of care alone in the second-line setting for patients with PSMA-expressing mCRPC. The trial is currently recruiting in Australia and enrollment is expected to start next year in the United States.

"TLX591 is being designed to integrate with current standard of care, demonstrative of Telix's continued innovation in prostate cancer treatment. The SELECT study provides further validation of the potential of TLX591, a first-in-class rADC therapy and the use of PSMA imaging with small molecules to select patients for antibody-based PSMA therapy,” Colin Hayward, chief medical officer at Telix, the developer of TLX591, stated in the news release.1

Reference

1. ProstACT SELECT Study of TLX591 Interim Readout: Positive Results Confirm Safety and Tolerability. Published online October 18, 2023. Accessed October 19, 2023. https://tinyurl.com/58a222yt

2. NIH. US National Library of Medicine. ClinicalTrials.gov. ¹⁷⁷Lu-DOTA-TLX591 Safety, Biodistribution and Dosimetry Study (ProstACTSelect). Last updated June 13, 2023. NCT04786847. https://classic.clinicaltrials.gov/ct2/show/NCT04786847