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I would agree with that for selecting the RP2D but they may want to go on and push the dose to see whether MTD is reached at the 310 level, which in total amount given would be equivalent to 465mg/m² of 3-weekly dosing (vs 385mg/m² in the final Q3W cohort). That would definitely be pushing it but they'd make their decision to do it or not based on the emerging side effects profile of the 2-weekly dosing.

465mg/m² given 3-weekly would be 6.2 times the standard 75mg/m² doxorubicin dose and higher than the lower maximum cumulative lifetime dose!

"Three patients now dosed in the US in two-weekly dose escalation study" was announced 7am on 21 March 2024. So that dosing was on 20 March in the US. Second dose would be 3 April. Two weeks for observation to 17 April. And "Avacta anticipates that the SMDC[sic] will review the two-weekly cohort 1 data by the end of April."

I presume JT means 310mg/m² which was C6 in the Q3W arm and would be C4 in the Q2W arm.

🤣 The usual baa-baa word salad I presume.

Which is sadder? Someone desperately trying to appear rich because of feelings of inadequacy or someone who's genuinely rich but needing validation from complete strangers on an anonymous BB?

Don't bother answering. It doesn't matter.

Icecool green binned for me as well PL. I was just going by the monikers I saw as latest posters in the thread.

What a pity. We were having a good discussion until icecool decided to wade in with his narcissist ego to give the trolls the oxygen to take this thread off topic. icecool you are the very definition of a twat.

Icecool is part of the deramping crew - or an idiot. The jury is out.

Please just ignore the trolls. They have neither the wit nor the will to understand and contribute.

Oops, obviously posted to the wrong thread...

Please just ignore the trolls. They have neither the wit nor the will to understand and contribute.

This is a granted (that's to say, IP is now protected by law) patent. I just hope Avacta can commercialise this Affimer invention, whatever it is - probably too complicated for anyone except an Einstein (who was a patent examiner) to dissect and understand.🤣🤣🤣

Here's a list of recent Avacta patent filings (no change since last shown): https://patents.google.com/?assignee=avacta&oq=avacta&sort=new

@Steelwatch200, City to United? 🤣🤣🤣

I'm ignoring the ignorant sealion's contribution which I'm sure is designed only to derail the discussion and whose trolling will only be taken up by the immature.

@Bella's "if he gets to a point where the trial cannot administer any further doses, for whatever reason, I'm sure he will be coached accordingly."

That would be reaching his lifetime cumulative dose, declining to continue, death (from whatever cause), unresolved side effects, etc (see the trial protocol). With a much reduced tumour mass he would have several options as I previously wrote - a different clinical trial (the guy seems to like them!), radiotherapy, surgery on the reduced tumours or return to any (obviously non-anthracycline) SoC there might be for his cancer.

160mg/mm² then, 160mg/mm² now.

There was the opinion expressed on here some time back that patients still on trial would be moved to the latest dose. That was the wrong opinion then and it would be the wrong opinion now. Anyone who doesn't immediately understand that should take a moment to consider what repeatedly upping patients' doses during the trial would do for understanding the response at each dose level; for understanding how AVA6000 works and what the RP2D should be..

@B2HS2L, that patient has two choices: continue being dosed at the 160mg/mm² level he has been on; or decline further doses. His part in the trial has not finished; of course it hasn't - it is important to see what the response is with long-term treatment: whether/when there is doxorubicin resistance; what level of tumour reduction can be achieved. He doesn't get to choose what dosing regimen he should be on any more than you get to choose what meds should get when you see your GP.

Maybe you should write to CC and take this up with her.

Scrap that. The percentage volume reduction will still depend on the shapes (long vs spherical) of the two tumours being measured as their morphology will not necessarily have changed, just shrunk, so back to somewhere between 26% and 59% shrinkage by volume.

Hi SW, thanks for the details about how tumour size is measured using RECIST 1.1 methodology. On that basis, the length will be arrived at more by measurement of a couple of sausages than a sphere, so much more on the length side. Precise percentage reduction still unknown but will be much closer to 26% than the 59%.

@B2HS2L, moving that patient to a more frequent (or higher dosage) regimen whilst his tumour was still being reduced by the dose and frequency he was on (that's to say, whilst his disease was NOT progressing) would have two effects:

For him, he would reach his lifetime limit sooner. I'm not sure he or his family and friends would thank you for that.

For the trial, further valuable long-term data for that 160mg/mm² dose level would not be possible. I'm sure Avacta wouldn't thank you for that.

Do you understand now?

A refinement to my earlier calculation...

The data for measurements of the longest axis of each tumour may be impressive, but the measurements of the volumes will be even more impressive. The tumours won't be spherical so the real volume decreases will be less impressive than for spheres - they will be somewhere between the reductions in sphere volumes and reductions in lengths - but using the volume of a sphere equation of v=(4/3)πr³ and website https://www.omnicalculator.com/math/sphere-volume the results are:

For length as d = 100mm, 35mm, 26mm

And r = 50mm, 17.5mm, 13mm

v = 523.6cm³, 22.45cm³, 9.203cm³

Size of tumour = 100%, 4.2876%, 1.7576% of original size

Quoted measurement reduction of 65% to 74% (26% of length) = 59% of volume

So, using the calculation for spheres (admittedly an overestimate), the reduction between the quoted 65% and 74% reductions (as measured by longest tumour axis) is about 59% of volume. The calculation on length is about 26%, so actual reduction of tumour size between those two scans would be somewhere between 26% and 59%.

I hope I've done the calculations correctly because these results are f'in amazing.

@B2HS2L, I'm surprised at some of your comments here. Are you Eggy in disguise?😉

- - - - -

"I could understand this patient, who must be due a scan shortly, must be feeling great to be alive, but possibly nonplussed to find the reduction in his tumour diameters were from 65% to only 74%."

If you look at it this way... The tumour was originally 100 units big, so 65% and 74% reductions have the tumour at 35 and 26 units respectively. A reduction from 35 to 26 is a reduction between those two, not necessarily consecutive, scans of 9/35 percent, which is 25.7%. On its own, this percentage reduction means very little because it is based on two, not necessary adjacent (and from the dates the data have been reported, I think not adjacent), data points and what is important is the RATE of tumour reduction, be that increasing, steady or decreasing - and all in the context of the tumour still growing (note: if cells have stopped dividing and the tumour stopped growing then it is no longer malignant, although it may be dormant). The scan measurements are not an exact science and there must come a minute size of tumour where the margin of error is enormous.

- - - - -

"If I were him I would have made representations to change present dose frequency to every two weeks. He could argue his response to AVA600 is stalling, and as he's been on drug since Feb 2023."

Good luck with that. Firstly, how do you know the response is stalling (see above)? Secondly, patients remain on cohort dosage (on trial) UNTIL DISEASE PROGRESSION. The reason for that is so that 'clean' data - data relating solely to that cohort's dosage level - can be collected. Nothing has been said about what happens when a patient's disease progresses - whether dosage is upped, frequency is now increased or dosing is stopped completely - and it will be a clinical decision based on the clinician's experience and knowledge of the patient's condition. The patient could move to a different trial, for example, or have surgery, radiotherapy or a further course of SoC chemo. What is certain is that any data collected about a patient's response after a change of dosing regimen will contain very little if any useful data (n=1 study) to inform about the RP2D level.