Phase 3 study launches exploring TLX591 in mCRPC

The first patient has been dosed in the phase 3 ProstACT GLOBAL study (NCT04876651) exploring the investigational prostate-specific membrane antigen (PSMA) targeting radio-antibody drug conjugate TLX591 (177Lu-rosopatamab tetraxetan) in patients with PSMA-positive metastatic castrate-resistant prostate cancer (mCRPC), announced Telix Pharmaceuticals, the developer of the agent, in a news release.¹

"Dosing a first patient in the ProstACT GLOBAL study is a significant milestone for Telix and will help build on an already extensive data set for this product candidate," says Colin Hayward, MBBS, FFPM.

The multinational, multicenter, prospective, randomized, controlled, open-label study is investigating second-line TLX591 in combination with the current standard of care (SOC) vs SOC alone in patients with mCRPC who have progressed on a novel androgen axis drug. The target enrollment for the study is around 400 patients.²

The first patient in the trial was successfully dosed at GenesisCare’s centre at the St. John of God Hospital Murdoch campus in Australia.

"Dosing a first patient in the ProstACT GLOBAL study is a significant milestone for Telix and will help build on an already extensive data set for this product candidate. The current TLX591 experience underlines the potential benefits of an antibody-based approach in combination with real world standards of care, including physician choice of ARPI[5] or taxane. As we take this potential first-in-class rADC candidate into a large, mid-stage patient population for the first time, we would like to thank Professor Lenzo and his clinical team, as well as the patients who will contribute to the study,” said Telix Chief Medical Officer Colin Hayward, MBBS, FFPM, in the news release.¹

The GLOBAL study is expected to expand internationally, including to the US and Europe, following regulatory approvals. The US arm of the study would include a run-in to bridge manufacturing data to a new commercial-scale process, with an interim analysis following dosing of the first 120 patients. Telix is on track to file an investigational new drug application with the FDA for TLX591 by the end of this year.

Additional data on TLX591

The ProstACT GLOBAL study builds on previous data from 242 patients across 8 phase 1 and 2 studies of TLX591, including the ProstACT SELECT trial (NCT04786847), which published preliminary results earlier this year.³

Data from the SELECT study showed that treatment with TLX591 resulted in a PSA reduction in nearly two-thirds (64%) of evaluable patients. Overall, 27% of patients had a 30% reduction in PSA, and 18% had a 50% reduction.

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 neutropenia 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.

In total, the study enrolled 30 patients with PSMA-expressing mCRPC. The efficacy population included 28 of these patients. TLX591 was given in 2 single intravenous infusions administered 14 days apart in all patients.

"Recent studies, including ProstACT SELECT, have further advanced the development of this antibody-based PSMA therapy for prostate cancer patients. We have been encouraged with the safety profile, tolerability, and early efficacy observed in our previous and ongoing studies, in particular for symptom control. It's an important step forward for patients to see this investigational therapy enter a Phase III study,” concluded principal investigator of the GLOBAL study and clinical director of theranostics for the GenesisCare Group Nat Lenzo, BSc, MBBS, in the news release.¹

References

1. First patient dosed in phase III ProstACT GLOBAL study of antibody-based prostate cancer therapy candidate TLX591. News release. Telix Pharmaceuticals Limited. November 12, 2023. Accessed November 13, 2023. https://www.prnewswire.com/news-releases/first-patient-dosed-in-phase-iii-prostact-global-study-of-antibody-based-prostate-cancer-therapy-candidate-tlx591-301985377.html

2. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. 177Lu-DOTA-rosopatamab with best standard of care (SoC) for the second line of treatment for metastatic castrate-resistant prostate cancer, which expresses PSMA (ProstACT). Last updated April 18, 2023. Accessed November 13, 2023. https://clinicaltrials.gov/study/NCT04876651

3. ProstACT SELECT Study of TLX591 Interim Readout: Positive Results Confirm Safety and Tolerability. Published online October 18, 2023. Accessed November 13, 2023. https://www.prnewswire.com/news-releases/prostact-select-study-of-tlx591-interim-readout-positive-results-confirm-safety-and-tolerability-301961317.html