Hi **eyBabe
Thankyou for your extremely kind words! Thanks in fact to everyone who has made comment on my post - much appreciated.
**ey, you ask a question: "Just to confirm or clarify: if B-vaxx had some problems, issues/ or was not going so well in Phase 2, we should know by now? If so, then logic would afford the conclusion that it's still going pretty bloody well after 4+ years? And why not an update? Do we expect this perhaps before end of 2021 or is IMU just too busy with all the other shots on goal atm?"
I can't give a definitive reply because I just don't know. Really - we will know the truth when Imugene releases the results of the study or at least an update. It is an “open label” trial so the researchers do know who is receiving the treatment and they will have a good idea how they are going – but they are not required to report results until those results have been properly gathered and analysed in a formal trial report. On the plus side, if there was a major problem then yes - I believe that would be market sensitive and it would require an Announcement. So for me, no Announcement so far is good news by default.
It is always possible they will give us some interim data but I don't expect to hear anything until the trial really is complete. And of course I have no way of knowing how the trial participants are going, but I do have some thoughts on the matter.
First up - I think that 4+ years is not the correct figure. It is 4+ years since the Phase 1 dose escalation trial, for sure, but the Phase 2 trial only started enrolments around 3 years ago. Even so - I think that is cause for considerable optimism. Here is my full explanation.
errr.... apologies .... it's a bit long!
The first mention of the “extension arm” is in the October 2016 trial update.
https://clinicaltrials.gov/ct2/history/NCT01376505?V_12=View#StudyPageTop
That update contains two significant new pieces of information.It confirms that the Phase 1 “dose-escalation (4 cohorts) has successfully completed with the accrual of 24 patients and the Optimum biological dose (OBD) has been determined as the dose at cohort level 2.”
It also announces for the first time that “The next phase of the study progresses directly into an extension trial at the OBD. 12 patients will be accrued at that level. The extension cohort will be open to only HER-2 and/or EGFR overexpressing cancers.”
The extension arm is not mentioned in any of the earlier updates andthe immediately previous update, on 1 March 2016, shows the dose escalation as still in progress.So we can see that the Phase 1 trial dose escalation completed sometime between 1 March and October – with a decision to move on to what they describe as an “extension arm” using the most effective dose level and ensuring that the new trial participants DO have a cancer which over expresses HER-2.My previous post explains why that last bit is so important to obtaining useful effectiveness data.
Now the addition of 12 patients in the “extension arm” only takes total trial participants to 36.That is – the 24 recorded as completing the Phase 1 dose escalation plus the 12 new patients for the “extension arm.”(A note is needed here:In their June 2019 paper detailing the Ph 1 study results the researchers state that in fact “Twenty-eight patients completed the 3 vaccination regimens.“https://clincancerres.aacrjournals.org/content/25/12/3495)
A Phase 2 clinical trial would normally be more than 40 or 50 patients, and as of October 2016 the “extension arm” was only shown as 12.That number is repeated in the clinical trial updates of 15/6/17, 3/4/18 and 19/7/19.Then on 24 July 19 a new update to the Clinical Trial repeats the earlier statement that “12 patients will be accrued” for the extension arm but the “Enrolment” field in the Study design section is updated and it shows an anticipated enrolment of 100 – up from the 36 shown just 5 days previously in the 19 July update.(The 100 participants figure has been maintained in all subsequent updates).
Coming so soon after the 19 July update I suspect that this is really a correction, and that the 19 July version wasmeantto show an enrolment of 100.Why do I think that?Well if you read through all the versions of the B-vaxx Clinical Trial on clinicaltrials.gov you will see that even now, as of the most recent update on October 11 last year, the study is still called a Phase 1 Trial.it still only refers to 12 patients being accrued for the extension arm and it still only lists one trial site (OSU in Columbus Ohio).However Imugene calls it a Phase 2 trial on their website and they were definitely referring to it as a Phase 2 trial right from the very beginning when they arranged the Ohio deal back in June 2018.
In the Imugene CR presentation for the Ohio licencing deal released on 7June 2018, page 20 names it as the “OSU/Mayo Phase 2 Her-2 Study” – with a target enrolment of 48 (12 extensionand 36 expansion).https://hotcopper.com.au/threads/ann-capital-raising-presentation.4232344/
The “36 expansion” has never made it into the clinical trial description on clinicaltrials.gov
The June 2018 presentation shows the current enrolment as just 3 and I am not aware of any further updates to that, but by July 2019 someone decided to update the “anticipated enrolments” to 100
We also have Imugene’s Announcement of 2 April 2019 regarding a presentation on Key-vaxx (now known as PD1-vaxx) and B-vaxx at the American Association for cancer research AGM, in which they state:“A Phase 2 study evaluating the activity of B-Vaxx in patients over expressing HER-2/nue is being conducted at renowned clinical institutions in the US. “(Note the plural “institutions”).
https://hotcopper.com.au/threads/ann-imu-presents-new-key-vaxx-and-b-vaxx-data-at-aacr.4695291/
In the Imugene Newsletter of June 2019, Leslie Chong states: “Our B-Vaxx Phase 2 study is recruiting to schedule at participating trial sites.“ (Note the plural “sites”).https://static1.squarespace.com/static/5b63d41b3e2d09b1f56bf483/t/5cf534c68c072e000127d604/1559573706876/IMU_FA_Newsletter_Jun19_web.pdf
Also, Prof Kaumaya himself refers to it as a Phase 2 trial in his paper published online in June 2020: “Given the initial promise, continuous development of the vaccine is ongoing in a Phase II trial at the suggested optimal biological dose (OBD) in a less heavily pretreated patient population in breast and/or gastrointestinal malignancies with HER-2/EGFR overexpression.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426751/
So this is telling us that the B-vaxx Clinical Trial entry on clinicaltrials.gov has not been kept up to date and that the Phase 1 “extension arm” was expanded to a full Phase 2 trial at least as early as June 2018 and probably earlier.
That gives us a Phase 2 trial which has been running for around 3 years and is scheduled to end after 3.5 years.
That is longer than most Phase 2 trials – though we do not know how long it took to get enrolments from the 3 shown on 7 June 2018 up to something more meaningful, and we do not know the current enrolment.
However I do see the length of time asprobablya very good sign. Why?
Well, if this was a Phase 2 trial in some kind of chronic disease (eg Arthritis) then a long term study would be no surprise at all because the disease would not be expected to kill the trial participants.
But this is a trial in patients who, sadly, by any reasonable expectation were expected to die from their disease, and probably quite rapidly.Trial participants are required to have “malignantmetastatic solid tumor; the malignancy should be considered incurable using standard treatment.“Patients included in the study have one of: breast cancer, ovarian cancer, colon cancer or other gastro-intestinal cancers and their cancer is already metastatic – spreading to other locations.All patients have been screened to ensure they have a cancer which over expresses HER-2 or EGFR (Epidermal Growth Factor).HER-2 and EGFR expressing cancers are more aggressive, because the HER-2 protein and EGFR promote rapid cancer cell growth.
All of the patients have tried normal standard of care treatments without success and their prospects are, really, quite dismal.
So for the trial to be still running and not scheduled to end until 31 December is, in my view, a very good sign.
We won’t know for sure until they say, and I doubt they will say anything until the study really is over, but I started this B-vaxx thread because I believe we are largely overlooking B-vaxx when it deserves a little more attention.
Now – let’s enjoy Sunday!!! If you are reading this, go get a life!!!!
Cheers
DaveJ
(20min delay)
