The PanTHa study is a phase I first in human study in men with metastatic castration resistant prostate cancer. What we looked at here is an actinium-based compound, so trillium combined to a Macropa for better chelation of the actinium compound. Now, the background of looking at actinium, an alpha-emitting agent, is to try to capitalise on the alpha emitter being more toxic to the cell, more linear kill, with less penetration so less off-target effects on the bone marrow and etc. So really to try to increase efficacy and reduce adverse events due to radioligand therapy.
The patients that we put in the PanTHa study were all metastatic castration resistant prostate cancer that had progressed on at least one ARPI and at least one taxane. So really a dose escalation study in the standard fashion with 3-4 patients per dose level and we looked at four different dose levels: 75, 100, 125 and 150kBq/kg.
What were the results?
The focus obviously for a first in human phase I study is to look at safety and make whatever we can in terms of opportunity to look at efficacy. So what we did was at the four different dose levels we had no DLTs. So in terms of safety there was nothing that prevented us from increasing the dose and in terms of dose reductions we didn’t really see anything major in terms of dose reductions until the 150 dose where three out of 12 patients, 13 patients, had to have a dose reduction.
Other safety issues were as expected. Xerostomia was the most common with almost 90% of patients having xerostomia but the vast majority being grade 1 and none had grade 3 or 4 xerostomia. So in terms of safety we were really quite pleased, very little haematological or renal toxicities with this compound.
Could you talk us through the efficacy?
We included a total of 50 patients, we had the 3-4 per dose and then we had a backfill since they were safe to use those doses. So we actually did 50 patients and what we saw was overall there was an over 60% PSA50 response and over 40% PSA90 response at the global overall. Specifically, at the 125kBq/kg dose, this is the dose that we were most interested in after looking at all the data, we’re up to 83% PSA50 response and over 60% PSA90 response. In terms of measurable response we’re over 70% measurable response rates with the 125kBq/kg dose. So this is going forward in the expansion part of the study that’s actually ongoing right now. So we’re very pleased, even though it’s still phase I, relatively small numbers, the efficacy and the safety is really quite encouraging to move forward eventually with a phase III study.
Is there anything else you would like to add?
We did perform some exploratory analysis in ctDNA and that correlated quite well with reductions of ctDNA with PSA responses. Again, coming back to the 125kBq/kg dose, we actually had 89% ctDNA reductions and over 30% complete eradication of ctDNA. So confirming that the 125kBq/kg dose looks like an excellent balance between efficacy and safety and we look forward to the expansion phase of the study which will include patients that are chemo-exposed, chemo-naïve and even are post-lutetium. So hopefully answering several questions to help us design the best phase III study we can.
