Study establishes proof of concept for TLX592 in prostate cancer

Results from the first-in-human early phase 1 CUPID study (NCT04726033) establish a proof of concept for the targeted alpha therapy TLX592 in patients with advanced prostate cancer, supporting advancement of the therapy into clinical trials.¹

Telix plans to initiate a phase 1/2 clinical trial of TLX592 with actinium-225 in the second half of 2024, pending FDA acceptance.

TLX592 utilizes Telix Pharmaceuticals’ RADmAb engineered antibody technology, which “accelerates blood clearance and reduces bone marrow residence time compared with standard monoclonal antibodies (mAbs), while retaining target selectivity, internalization, and retention,” according to the company.¹

The CUPID study also utilized copper-64, which is detectable via PET imaging and acts as a surrogate for actinium-225, which may be used in future studies. Earlier this month, Telix announced an agreement with Cardinal Health Nuclear & Precision Health Solutions to support the clinical supply of actinium-225.²

Overall, preliminary results from the CUPID study were based on data from 11 evaluable patients. The findings showed accelerated elimination from the blood circulation compared with that of the standard antibody TLX591. Additionally, TLX592 demonstrated similarly favorable on- and off-target biodistribution and hepatic clearance.

No serious adverse events were reported.

The CUPID study is designed as a 3+3 dose escalation study with 4 patient cohorts. Patients were enrolled at a single center in Australia. The primary outcome measures are the number of participants with treatment-related adverse events, as well as the pharmacokinetics, biodistribution, and dosimetry of TLX592.³

"The CUPID study demonstrated clearly how theranostic approaches can be used to streamline novel radiopharmaceutical drug development. In this case, PET imaging was used to dose-find a targeting agent for future use with an alpha emitter, while establishing basic safety and utility parameters that will greatly inform ongoing development of this product candidate,” said David N. Cade, Group Chief Medical Officer at Telix, in the news release.¹

Based on the results from the CUPID study, Telix plans to initiate a phase 1/2 clinical trial of TLX592 with actinium-225 in the second half of 2024, pending FDA acceptance.

"There is a significant unmet need for novel targeting platforms that may be used with alpha emitting isotopes and avoid renal toxicity and other off-target effects, such as the exocrine gland uptake typical of PSMA small molecule agents,” Cade added in the news release.¹ “We are excited to progress TLX592 into therapeutic studies where our aim is to develop this agent for both early metastatic prostate cancer and late-stage patients who are no longer responding to lutetium therapy. We would like to thank all participants for their commitment to the CUPID study.”

With TLX592, Telix further expands its therapeutic portfolio, which also includes the investigational radio antibody-drug conjugate TLX591 (177Lu rosopatamab tetraxetan). TLX591 is currently being studied in the phase 3 ProstACT Global trial (NCT04876651), which is enrolling adult patients with PSMA-positive metastatic castrate-resistant prostate cancer (mCRPC).

The first patient in the study was dosed in November 2023,⁴ and the trial has an overall target enrollment of approximately 400 patients.

Overall, 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 primary end point for the study is radiographic progression-free survival. Secondary end points include overall survival, tumor objective response rate, and time to first symptomatic skeletal event.⁵

Primary completion of the ProstACT GLOBAL study is expected in June 2025.

References

1.Telix completes proof-of-concept study of TLX592 targeted alpha therapy in prostate cancer. News release. Telix Pharmaceuticals Limited. May 20, 2024. Accessed May 21, 2024. https://www.prnewswire.com/news-releases/telix-completes-proof-of-concept-study-of-tlx592-targeted-alpha-therapy-in-prostate-cancer-302150652.html

2. Telix and Cardinal Health complete global clinical supply agreement for actinium-225 for targeted alpha therapy pipeline development. News release. May 8, 2024. Accessed May 21, 2024. https://telixpharma.com/news-views/telix-and-cardinal-health-complete-global-clinical-supply-agreement-for-actinium-225-for-targeted-alpha-therapy-pipeline-development/

3. 64Cu-TLX592 phase I safety, PK, biodistribution and dosimetry study (CUPID Study) (CUPID). ClinicalTrials.gov. Last updated May 1, 2024. Accessed May 21, 2024. https://clinicaltrials.gov/study/NCT04726033

4. 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 May 21, 2024. https://telixpharma.com/news-views/first-patient-dosed-in-phase-iii-prostact-global-study-of-antibody-based-prostate-cancer-therapy-candidate-tlx591/

5. 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). ClinicalTrials.gov. Last updated April 18, 2023. Accessed May 21, 2024. https://clinicaltrials.gov/study/NCT04876651