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Last business day of Q3, when final DSMC decision was supposed to be made. Perhaps it takes them a few days/weeks to prepare the announcement.
Was it confirmed that this patient was on the VB-111 arm?
If true then it would be great IF avastin performs to historical data. But we don't know how the 105 breaks out ... or do we?
Haha ... I wish!
DSMC decision any day now. I would think the decision will come this week. Or at the latest next week if they need extra time to process and finalize their findings.
Yes, this methodology is what I think they're using.
Do you know the sequential monitoring methodology and why the DSMC uses it?
If you look at the Sept VBL slides that wcopeland linked, it clearly says N = 29 for that particular trial. That slide has the sample size for all the trials, including the year, median age, median survival, etc. It's all on that slide. 8 trials that they summarized in one slide.
Thank you, wcopeland, that was my exact thought. The information is there in the Sept presentation. Click on it. Open it. Read it. It's not so hard. The presentation was shared a long time ago.
For the newbies, do some research. Search the older discussions. Chances are, we have exhaustively discussed it. It may be new to you but many of the posters that have been here for a while have discussed it already.
If you don't find it, respectfully discuss it. No need to be sarcastic or arrogant about it.
Exactly. I'm not sure how you can analyze safety without reviewing efficacy.
My understanding all along is that the DSMC safety review includes efficacy (factoring it in but not reporting it out). This is also mentioned in numerous documents. Dror's comments seem to support what I've said.
Dror Harats
Basically, we are looking safety and that’s their charter. But as we all know, they look at survival as part of or the death event as part of safety of course. And because our primary endpoint is death, or the event are actually survival, then of course there is no way that you can separate it completely. But the major thing is that they are looking at safety, but of course, we do understand that they look at survival as well.
You're getting them confused. Read your own link, page 17: 4.4.1.2. Monitoring for Safety
Efficacy is reviewed in monitoring for safety; they just won't report it out.
The quote you provided from the CEO is one with him saying that they will not report out interim data. DSMC is still reviewing for safety (which includes efficacy).
I posted this earlier this month. Note the last point.
Good read on what DSMC is and is not:
https://ippcr.nihtraining.com/handouts/2015/Shaw_Pamela-01-05-16-Full_Slides.pdf
Note on slide 24, Why Data and Safety Monitoring::
• To identify any safety problem rapidly
• To identify logistical problems
• To evaluate continued feasibility of trial
• To determine if trial objectives have been met and trial may be terminated early
Something to consider as we approach the DSMC decision for the interim.
Dude. Stop with the childish sarcasm. No need to be that way.
DSMC does do an efficacy review. So no they're not guessing. Do some research on the trials that have stopped early.
Agree that median OS has been reached for both arms - assuming Avastin and VB-111 behave like they did historically and in phase 2, respectively.
DSMC can stop the trial early due to good/bad reasons. In this case, if it were to stop it would be for a good reason.
However, I don't think this trial will stop early. VB-111 may be an improvement but not enough to stop the trial early so that patients on the Avastin arm also get VB-111.
This week is cool. We're getting the DSMC decision - hopefully good. Then it's on to the final topline data.
@mantoo, take a look at slides 5 and 6 in the company's presentation.
http://ir.vblrx.com/static-files/9b1c10ac-65b5-4867-9100-0c25ab7a1a9c
Correct mantoo123. This is what I wrote back in June:
From ASCO, it is good to see that the continuous exposure (CE) group had lower KPS and higher rate of 2nd recurrence BUT achieved longer median OS.
Notes from ASCO:
The overall response rate (ORR) for the continuous exposure group was 29% (7/24), and 2 patients experienced complete responses. (CRs) One of the CRs occurred using single-agent VB-111, and the patient remains in remission as of 39 months. Notably, patients in the continuous exposure group had an overall lower Karnofsky performance status (KPS), a less successful initial resection, and had a higher rate of second recurrence than the limited exposure group at baseline, increasing our confidence in the prior survival results with VB-111.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=132017781
Agree davidal66. They may know those numbers in aggregate. However, since they are blinded, they won't know specifically when those patients were recruited and how many doses each received.
The failure of VB-201 in psoriasis and ulcerative colitis in phase 2 is now a positive factor for the company, imo. It shows that if a treatment is not working, the company will stop it early. This can be grouped in the positive factors bucket (like facilities, Thai Lee, upcoming OVAL study, etc). They are positive signs that the company is doing the right things but they don't impact the phase 3 GLOBE results.
Until more concrete indications come out from DSMC and FDA, this is all we have for now.
VBLT @WallStPirate ... I agree. A lot will happen in the next 3-5 months.
Agree wcopeland. Those are all good "signs" (including DSMC decisions) but none of them can conclusively say ph3 will pass. Only ph3 patient outcome will determine that. But the FDA can bend the rules a little bit like they did with avastin, which, as we all know, does not improve mOS.
They only have the final DSMC review before the final top-line data in 2018. If you want to call that interim then fine. But the original interim report has been canceled -- it is not happening.
I also questioned the true reason for canceling interim. The reasons given for canceling interim were weak, imo. But it was done with the FDA's blessings so I took that as a good sign.
Companies report out only if they have to, right? So if the FDA is saying no need to report we'll handle it through the DSMC, it's not all bad, imo.
I think the truth (or bits of it) will come out early next year.
The median OS numbers for avastin and VB-111 has been reached, imo. Someone (few) knows those numbers.
Doctors and patients are starting to learn that if avastin doesn't help, it has devastating side effects. It's just not worth the risk.
If they had a choice, they would pick VB-111. Even if it doesn't help, it wouldn't ruin the patient's health like avastin.
How many "others" are self made billionaires?
Thai Lee just increased her ownership by almost 10%. Sole voting power increased. Aggregate increased.
Look at the numbers from Jan-16 to Sep-17:
Thai Lee Family Trust
SHARED VOTING POWER
Jan-16: 4,858,739
Sep-17: 2,192,007
Thai Lee
SOLE VOTING POWER
Jan-16: 0
Sep-17: 3,074,069
AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
Jan-16: 4,858,739
Sep-17: 5,266,076
Filing Date Sep 18, 2017
http://ir.vblrx.com/sec-filings/sec-filing/sc-13da/0001615774-17-005152
Filing Date Jan 19, 2016
https://www.sec.gov/Archives/edgar/data/1603207/000161577416006946/s103558_sc13d.htm
@Prov - where do you see this? Their news release said Monday, 9/11
http://ir.vblrx.com/news-releases/news-release-details/vbl-therapeutics-present-rodman-renshaw-global-investment
The link to their presentation says, "This presentation has been canceled." Not sure if they presented.
http://wsw.com/webcast/rrshq27/vbl/index.aspx
I'm probably wrong but my guess would be speculative buying before the DSMC decision / Cantor Fitz presentation.
Although there were some exclusion criteria, not restricting tumor size makes the term "all comers" more true.
Also, take a look at phase 2 baseline characteristics on pg 2. CE had worse group but performed better.
http://www.lifescicapital.com/wp-content/uploads/LSC-ASCO2017%E2%80%93Highlighted-Company-Presentations2.pdf
You may be right. I agree that median OS has been reached, but not so sure about the results. If avastin is similar to historical results then VB-111 has a chance to perform better. But as good as ph2 results? Not so sure.
I'm wary of avastin. A few people stated that it helped them so perhaps it is effective with a small subset of patients. Otherwise, I have seen numerous examples of patients greatly suffering after taking avastin.
By debulking the tumor mass,
VB-111 may enhance the activity of standard anticancer
agents and may be a potential candidate for
neoadjuvant therapy. Unlike other antiangiogenesis
approaches designed to block specific cellular
steps in processes leading to new blood vessel production
or cellular proliferation, VB-111 destroys
existing vascular endothelial cells. VB-111 may be
effective both as a monotherapy and neoadjuvant
therapy and in combination with chemotherapy or
radiotherapy. It may be applicable to many different
types of solid tumors where vascularization is a
key driver of growth and metastasis.
In preclinical studies in multiple tumor models,
VB-111 was tumor-tissue specific and did not significantly
damage normal tissues or blood vessels.
In vitro, VB-111 induced a dose-dependent apoptotic
death in HUVEC but not in non-endothelial
cells, confirming its specificity. In in vivo studies
using the Lewis lung metastasis mouse model,
VB111 was safe and active only in metastatic lesions
and, with one injection, reduced tumor burden
of lung metastases by 90% in a dose-dependent
manner. IN this same animal model, the addition
of VB-111 enhanced the activity of Sutent. An
additive effect was also observed when mice were
treated with VB-111 and doxorubicin. VB-111
was similarly efficacious in other tumor models.
Overall, VB-111 was found to be safe and tissue
specific with a dual mode of action as an angiogenic
inhibitor and VDA (Breitbart A, et al., AACR10,
Abs. 1369). Based on these preclinical results, VB-
111 entered clinical trials in November 2007.
In a completed phase I clinical trial (protocol ID:
GT-111001; NCT00559117) VB-111 was administered
as a single IV infusion at escalating doses
ranging from 1x106
to 3x1012 viral particles (VP)
in 6 successive cohorts. Between November 2007
and August 2009, 27 patients enrolled at two cancer
centers. VB-111 was well tolerated; no DLT
≥Grade 3 were observed. As expected from the
specificity of VB-111 the Fas chimeric transgene
was not expressed in the blood. Disease stabilized
on day 56 in one of the 15 patients in cohorts 1
to 5. Among the 12 patients in cohort 6, disease
stabilized in 4 on day 56, and there was a PR in
one patient with papillary thyroid carcinoma that
persisted for 12 months post dosing. VB-111 was
safe and well tolerated in patients with advanced
metastatic cancer at a single administration of up
to 3x1012 VP. MTD has not been reached (Triozzi
P, et al., AACR10, Abs. 1361). Currently, the drug
is in phase II clinical trials in relapsed glioblastoma
multiforme (GBM) and advanced differentiated
thyroid cancer.
======================
^This was written in 2011 and it's still true today.
http://www.newmedinc.com/futonc/sample.pdf
I agree. Not sure they presented.
All other presenters had live link and archived presentations. VBL did not.
I hope you're right ... and you would be right if Avastin results are similar to historical.
"Since BEV survival in this trial will not be very different from the historical rate (as being calculated both on big numbers), my assumption is that the VB111 numbers in ph3 will show a much better result than what was shown in ph2 (maybe due to the fact that in this trial the combination VB111 + BEV is for the whole treatment and not just a part of it as in ph2) "
Wouldn't this make a case to justify stopping early?
Aug 2015: First patient dosed. It has been over 2 years since the trial started.
Jan 2017: Completion of enrollment. It has been 8 months since completion of enrollment.
Avastin's median OS is 8 months and there has been 12 months of follow up for 50% of the patients, so I think there is enough data there for the DSMC to determine VB-111's effectiveness. I see 3 scenarios for DSMC decision at the end of this month:
1) VB-111 combo is worse than Avastin in mOS: DSMC will recommend to stop the trial.
2) VB-111 combo is as good as Avastin: DSMC will probably recommend to stop the trial since VB-111 is not providing any additional value. But they may not if there is a subset of VB-111 patients that are showing superior results.
3) VB-111 combo is better than Avastin: DSMC will recommend to continue. VB-111 is doing better. But we don't how much better. If DSMC approves and recommends that the trial continue then I would assume that VB-111 is doing better but not good enough to stop the trial early.
Either extremes (good / bad) will stop the trial but I get the feeling it will be somewhere in between with VB-111 arm performing better than Avastin's arm. Probably not as good as phase 2 results but good enough to pass phase 3.
Good read on what DSMC is and is not:
https://ippcr.nihtraining.com/handouts/2015/Shaw_Pamela-01-05-16-Full_Slides.pdf
Note on slide 24, Why Data and Safety Monitoring::
• To identify any safety problem rapidly
• To identify logistical problems
• To evaluate continued feasibility of trial
• To determine if trial objectives have been met and trial may be terminated early
Something to consider as we approach the DSMC decision for the interim.