Medicine Matters oncology

So at ASCO, we're presenting the initial results of the TheraP trial. This is a randomized phase 2 trial of Lu-PSMA-617 compared to cabazitaxel in men with metastatic castration-resistant prostate cancer who have progressed after docetaxel. And this was an investigator-initiated trial run by the ANZUP Cancer Clinical Trials Group in Australia and funded by the Prostate Cancer Foundation of Australia.

This was a 200-patient trial with 100 men randomized in each arm, one to one, Lu-PSMA versus cabazitaxel. The trial completed accrual last year, and the primary endpoint, which is PSA response, defined by a PSA reduction of more than 50% from baseline, was positive with a 66% of men in the Lu-PSMA arm achieving a PSA 50 response rate, compared to 37% in the cabazitaxel arm. So that's a 29% absolute greater PSA 50 response rate with Lu-PSMA compared to cabazitaxel. And that really met our predefined endpoint of more than 20% absolute improvement in this primary endpoint.

We also report some of the initial results of some secondary endpoints. These require ongoing follow-up to define them definitively. Most importantly, PSA progression-free survival appears to be prolonged in the Lu-PSMA arm, with a hazard ratio of 0.69. And we also looked at adverse events between the two arms, and we saw grade 3 or 4 adverse events were greater with cabazitaxel. Occurred in 54% of men who received cabazitaxel compared to 35% of men who received Lu-PSMA.

Could you put these results in context of the CARD trial in the same setting?

So this is, to some extent, a similar population to the CARD trial, which really showed that cabazitaxel is a relevant and active treatment in these men. And we started this trial obviously before the CARD trial was available, so this was on the basis of previous results showing that cabazitaxel improved overall survival compared to mitoxantrone. But I think our results are now even more relevant now that the CARD trial is published, because essentially what we're showing is, in this population, if you have a choice between cabazitaxel or Lu-PSMA, it appears that Lu-PSMA is more active than cabazitaxel as marked by the higher PSA response rate with relatively fewer grade 3 to 4 toxicities and a PSA progression-free survival favoring Lu-PSMA.

What we're waiting for in this trial is ongoing follow-up, which will define radiologic progression-free survival, quality of life, and overall survival. And we hope to have those results later this year. The take home line is probably that the results of this-- it's the first randomized trial of Lu-PSMA presented anywhere.

There is a American industry-sponsored trial called the VISION trial you're probably aware of, which has not been reported yet. And this trial has, I think, an active control arm being cabazitaxel, whereas the VISION trial really has a S standard of care control arm, which was quite limited. It was more like the CARD trial, sort of abi-enza crossover in patients that had already had abi-enza as of the control arm. So we think we have a more real-world, active control arm in this study. But the results really do tell us that Lu-PSMA represents a potential new class of effective therapy for these men with metastatic castration-resistant prostate cancer.