Radio–antibody drug conjugate demonstrates promising rPFS in mCRPC

The lutetium-labelled radio-antibody-drug conjugate TLX591 (177Lu rosopatamab tetraxetan) demonstrated promising radiographic progression-free survival (rPFS) among patients with metastatic castration-resistant prostate cancer (mCRPC), according to additional data from the phase 1 ProstACT SELECT trial (NCT04786847).¹

In addition to ProstACT SELECT, TLX591 is also being studied in the phase 3 ProstACT GLOBAL trial.

According to a news release from Telix Pharmaceuticals, the study reported a median rPFS of 8.8 months among 23 adult patients with previously treated, progressive mCRPC.¹

In total, the SELECT trial enrolled 30 patients with PSMA-expressing mCRPC across clinical trial sites in Australia.² Of those, 28 were included in the evaluable population. Cohort 1 of the study included 5 patients who received a 27 mCi dose of TLX591 followed by a 76 mCi dose. Cohort 2 of the study included 23 patients who received 2 intravenous infusions of 76 mCi TLX591 administered 14 days apart.

The primary end points for the study are the determination of the whole body biodistribution and organ radiation dosimetry, in addition to safety and tolerability. rPFS is a key secondary end point.

Preliminary results from the ProstACT SELECT trial were previously reported in October 2023.³ Data showed that treatment with TLX591 resulted in a PSA reduction in nearly two-thirds (64%) of evaluable patients. Among those, 27% of patients achieved a 30% reduction in PSA, and 18% achieved a 50% reduction.

The investigators also observed consistent lesion delineation between TLX591 and 68Ga-PSMA-11 imaging as well as positive uptake and retention in tumor and metastases at up to 14 days following injection with the therapy.

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

Nat Lenzo, MD, a nuclear oncologist, general internal medicine physician, and lead recruiter onto the SELECT trial, said in the news release of the findings, "We are encouraged by this rPFS result, which compares favorably to small molecule radioligand therapy phase 1 and 2 studies at similar stages of development. This is a compelling signal of the potential efficacy of TLX591 in this heavily pre-treated population. The results further support the development of this candidate in an earlier mCRPC patient population, which is the focus of the ProstACT GLOBAL Phase III trial and where there remains significant unmet need for effective treatment."¹

In addition to ProstACT SELECT, TLX591 is also being studied in the phase 3 ProstACT GLOBAL trial (NCT04876651), which is now preparing to enroll patients at its first trial sites in the United States. The study is comparing TLX591 plus standard of care with standard of care alone in the second-line setting for patients with PSMA-expressing mCRPC.

In total, the trial plans to enroll nearly 400 patients with PSMA-positive mCRPC across sites in the United States and Australia.

References

1. Telix announces positive rPFS data from ProstACT SELECT trial of TLX591 rADC therapy candidate in prostate cancer. News release. Telix Pharmaceuticals Limited. May 30, 2024. Accessed June 6, 2024. https://telixpharma.com/news-views/telix-announces-positive-rpfs-data-from-prostact-select-trial-of-tlx591-radc-therapy-candidate-in-prostate-cancer/

2. 177Lu-DOTA-TLX591 safety, biodistribution and dosimetry study (ProstACTSelect). ClinicalTrials.gov. Last updated February 12, 2024. Accessed June 6, 2024. https://clinicaltrials.gov/study/NCT04786847

3. ProstACT SELECT Study of TLX591 Interim Readout: Positive Results Confirm Safety and Tolerability. Published online October 18, 2023. Accessed June 6, 2024. https://telixpharma.com/news-views/prostact-select-study-of-tlx591-interim-readout-positive-results-confirm-safety-and-tolerability/