Hey friend @Taureanbull !
This is a reply to your post above. (The "reply" function wasn't working).
Oh no worries mate. Yes - there is just so much happening with IMU. omg....
And yep - we should get lots more solid data out of the MAST trial this year. It's going to be really interesting to see where OBD finally lands.
I believe T-VEC is still the only Oncolytic Virus approved by the FDA - in use against Melanoma since 2015. My understanding is that TVEC is administered in does of 4ml, at 108/ml - making it 4 x 108 (400 million PFU) total. (In the Phase 3 trial, the first dose was 4 x 106 and subsequent doses were 4 x 108). The report of the clinical trial does have a beautiful photo sequence of a patient with shocking melanoma lesions on her foot which disappear over a 12 month period. Marvellous!! Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003308/
The MAST trial is now at 3 x 108 (Cohort 5)- so basically the OBD used for TVEC. They are definitely planning to try a cohort 6 at 109 - as long as the current dose of 3 x 108 shows a significant increased effectiveness, and no dose limiting toxicity. Their latest conference poster shows a possible Cohort 7 at 3 x 109.......
Now - in the process of looking at all this, I discovered something really interesting. Well - interesting to me, at least.
The recent Poster presentation on the MAST trial contains a diagram showing the trial design. It includes the expansion cohort for Biliary Cancer, but it also shows a possible second expansion cohort - for "Metastatic Head and Neck Squamous Cell Carcinoma." (MHNSCC) Source: https://static1.squarespace.com/static/5b63d41b3e2d09b1f56bf483/t/65a9aff332d3180e08db85c7/1705619461250/749+ASCO-GI+MAST-Final+%281%29.pdf
That little detail gained some comment here on Hot Copper - and I speculated about it here too. We don't know the break up of patients by cancer type, in the MAST trial, so we don't know if they have any patients so far in that MHNSCC cancer type. My guess was that maybe they have had one or two, and they are seeing stable disease. MHNSCC is a cancer type with very poor prognosis for patients - no great treatment options.
Now - reading up further about TVEC - I discover that although TVEC was initially approved for Melanoma, it has also been trialled against - you guessed it - MHNSCC.
In Melanoma, the major Clinical Trials of T-VEC showed gave it a response rate in Melanoma of 26.4% and a durable response rate of 16.3%. And that was good enough for the FDA to approve T-VEC for user against Melanoma. Which I guess sets some kind of benchmark to compare with the MAST trial, as that data develops.
However, when trialled against MHNSCC, T-VEC was disappointing:
"In a phase Ib/III multi-institutional clinical study, T-VEC was evaluated in combination with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (Harrington et al., 2020). Thirty-six patients were entered into the phase Ib portion of the study and data was reported at a median follow-up of 5.8 months. Ten patients (27.8%) of the patients were not evaluable for response due to early mortality. A confirmed partial response occurred in 5 (13.9%) of patients. The authors concluded that while treatment was generally well tolerated combination therapy was not associated with a benefit compared to historical studies with pembrolizumab alone and the phase III portion was not pursued further. "
Source: The above stats on TVEC responses, and the info on the MHNSCC, are from this journal article:
https://www.frontiersin.org/articles/10.3389/fmolb.2022.834841/full#:~:text=The%20durable%20response%20rate%20was,after%2012%20months%20was%2073%25.
So I think this is probably a major reason why IMU is considering an expansion in Metastatic Head and Neck Squamous Cell Carcinoma. A good result would show Vaxinia as succeeding where the only current FDA approved oncolytic virus gas been shown to fail.
Of course, we also now have two Partial Responses in Melanoma on the MAST trial. I would bet that if either of those PR's improve further to Complete Response, and/or if they get as good or better results from further Melanoma patients - IMU would consider an expansion cohort in Melanoma. If they can show that Vaxinia is superior to T-VEC in the very cancer type for which T-VEC was approved for use...... Well - that would be a huge attention grabber.
The whole article referenced above is really worth a read, for anyone interested in T-VEC. Fort example - "the mean time to response" on the original T-VEC trial was 4.1 months, and (just as with Vaxinia) they saw examples of "pseudo progression" - where patients appeared to get worse, and then improved! Which is why I am very hopeful that some of the current MAST trial patients will actually improve on their most recently reported results - IF they stick with the treatment.
There are other points of interest, but I don't have time to bore everyone again right now. Aren't you lucky!
Cheers
Dave
(20min delay)