SHOW ME BETTER RESULTS – I would love to buy that stock!
For a fuller appreciation of the results of SECURE, we need to look, not just at SECURE versus SECURE (which we got into due to some of the results) - but we should cast further, and contrast with the wo is who in the field: what competing products are out there for the same indication, and what results have they achieved in their trials. That's the existing ceiling which we seek to reach and if possible, get past.
Match the competition, and the clinicians will give your product a chance: beat them, and your product moves towards becoming first line, unless other competing matters (access, including budget and physical access) get in the way!
We also need to remember: SECURE is a dose determining study! While we celebrate the efficacies, we should still judge the study for what it is. These are signals of what might (or is likely) to be achieved in a bigger trial! But its not certain.
Clarity are not only using the study to determine the sweet spot on safety and efficacy: they are using it to zone in on the best patient groups to target. This second objective is for the purpose of improving the chances of success in the upcoming pivotal trials, where another decision will be made: do we do a SUPERIORITY TRIAL and decimate the competition (risk of failure is higher), or we go with the less risky NON INFERIORITY TRIAL to be more certain of seeing 67CuSar-bisPSMA get into patients as an FDA approved trial, in a shorter time frame! The cohort expansion will give Clarity the answers needed to go forward. From what we know, Alan wants a head to head with SOC (whatever the patients can get)!
In our comparisons, we note that PLUVICTO is currently the GOLD STANDARD TREATMENT in this group of drugs, hence, we should look at PSMAfore and VISION as the appropriate yardsticks!
I will use PSMAfore as it has shown better results than what VISION trials got (better safety and effectiveness). That's because PSMAfore is looking at earlier stage than VISION! The cohort expansion is going for that same group.
TARGET POPULATION:
- PSMAfore targeted pre-chemotherapy mCRPC (taxane naive patients). This is an earlier group of patients than what VISION had (post chemo). And - this group has had better results than those in VISION.
- PSMAfore specifically excluded previous PSMA-targeted radioligand therapy.
- SECURE has everyone and anyone, including participants who failed PLUVICTO as well as Actinium 225 (an Aplha therapy). The participants include many who would not even have been allowed into VISION. These are very high risk patients, in whom chances of success should be lowest.
- SECURE has 13 pre-chemotherapy mCRPC participants in its cohorts: it’s the ones that had a 92% PSA improvement! This is the group that is to be the target for the next part of the trial, and is covered by the FDA Fast Track Designation for Cu-67 SAR-bisPSMA!
- The approach here is similar to what's happening with CLARIFY (pre definitive therapy) and AMPLIFY (cancer recurrence)!
SAFETY
PSMAfore had 34% Grade 3-4 TEAEs (that’s 1 in 3). Today, we heard about the FIRST case with Grade 4 in SECURE, overall!
In the PSMAfore trial, 1 in 20 who received Pluvicto had to discontinue treatment due to TEAEs.
EFFICACY
On Complete responses: PSMAfore had 21% after up to 6 doses of Pluvicto, while the SECURE trial had 1 in 3 in cohorts 3 and 4, after no more than 2 doses. So far, there have been no progressive diseases in SECURE (versus 15% in Pluvicto).Other data
IN CONCLUSION
- SECURE is a dose determining study. In other words, we did not know what dosage to use in a future trial where 67Cu-Sar-bisPSMA will be evaluated versus SOC (including Pluvicto) – until today! The dose has been determined: its 8 GBq! This is in the same range as Pluvicto (7.8 GBq). Also, the doses will increase to up to 6 - like Pluvicto.
- 12 GBq was good too, but there was one DLT for no apparent additional benefit! So, it gets dropped.
- The expansion and extension will set Clarity up nicely for a Phase 3 trial in a large indication: pre chemotherapy patients. FIST LINE therapy is in sight!
- I expect (and hope) we will return to the later stage patients - BCR etc in the Phase 3. They need the treatment! It may be that the big trial will have the different groups included - it would have to be really large!
LINKS
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