A pleasure to present the results from part 1 of the phase III ProstACT global trial that aims to evaluate the 177Lu-rosopatamab tetraxetan, also known as TLX591, in combination with standard of care in patients with metastatic castration-resistant prostate cancer.
What was the study design?
The ProstACT global phase III trial is a trial that consists of two parts, part 1 and part 2. The part 1 looks into the safety and dosimetry lead-in. It was designed to enrol 30 patients who met eligibility criteria, basically who had progressed on a prior ARPI and have evidence of metastatic castration-resistant prostate cancer. Those patients are allocated to one of three cohorts – a combination of TLX591 with abiraterone, one cohort, the other cohort a combination of TLX591 with enzalutamide and a third cohort, the sequence of TLX591 followed by docetaxel. In all the cohorts a TLX591 dose of 76 millicurie, fixed dose regimen two weeks apart in this trial. So that’s part 1.
The part 2 is the randomised expansion portion of the trial. It has a 2:1 randomisation or allocation of standard of care of either ARPI or docetaxel, so abiraterone, enzalutamide or docetaxel allowed as standard of care, plus/minus TLX591 in the fixed two-dose regimen that I described earlier. It’s planned to enrol approximately 490 patients and it has radiographic progression free survival as the primary endpoint and overall survival as the key secondary endpoint.
What were the results of the study?
When we look at the results of the part 1 ProstACT global study we observe a safety and tolerability profile across TLX591 with the standard of care of either ARPI or sequence docetaxel. We’ve seen a sustained tumour-associated signal on imaging through day 15 following the first dose of TLX591 with a prolonged tumour retention observed. Finally, we have highlighted the feasibility of this two-dose fixed regimen, basically supporting this treatment compliance and integrating TLX591 with the standard of care in mCRPC that can include either an ARPI or taxane-based chemotherapy.
What is the clinical significance of these results?
In my opinion these results from the safety lead-in and dosimetry data are meaningful because they support this manageable safety profile of this novel or unique approach with an antibody-based strategy with radioligand therapy. We have seen relatively low salivary gland and kidney radiation exposure as well so we think it’s a favourable safety profile there. This sustained tumour-associated imaging and feasibility of integrating TLX591 with ARPI and docetaxel-based strategies. So basically these findings do support the ongoing investigation of TLX591 on a larger scale and that’s exactly what’s ongoing with the ProstACT global trial. So I think the part 1 of the study helps us or validates the approach of a broader intervention that’s happening at the global scale. So it’s encouraging from that perspective.
