has gone from recruiting to Active not recruiting on clinicaltrials.gov. So enrollment must be complete as of 8/6/2015. Additionally the enrollment number has been updated from anticipated 150 to 165 actual in this randomized PH II trial.
Reo and Gem primary outcome was:
Determine the clinical benefit rate (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD))in the study population [ Time Frame: 4 weeks ]
Secondary outcome was:
Determine the progression-free survival of this combination in patients with advanced or metastatic pancreatic adenocarcinoma. [ Time Frame: 9-12 months ] [ Designated as safety issue: No ]
There was no OS end point. However in the 11/9/12 poster presentation they stated prolongued SD was being noted. So it looks like they followed the patients for at least two to three years and that is how they came up with the 45% one year and two year 24% survival numbers as well as the 10.5 month median OS number for the combination Gem/Reo - something that I believe was totally unexpected. And it points to a two pronged killing methodology - immediate cytotoxic killing of cancer cells and more importantly a longer term immune system ability to recognize the cancer and attack it immunologically. It also points to a disconnect between PFS being predictive of OS because of the two distinct killing methods of the treatment.
In the Reo/Pac trial primary outcome was:
Progression-free survival using RECIST v. 1.1
A secondary outcome was:
Overall survival [Time Frame: From study entry to the time of death due to any cause, assessed up to 4 years ]
Patient enrollment ended on July 8 2014 and Saab made his video on the trial (based on PFS KM) shortly after - canning the trial while admitting there probably were some responses. He did not wait to see OS which is tracked for 4 years. At that time I don't think the company or Saab was aware of the PFS OS disconnect in Gem/Reo - first reported 3/5/15 at the Irish cancer conference. It is entirely possible yet that this trial can be successful in long term survival and median OS as the Gem/Reo seems to be. However it also might not be and if not that will not negate the impressive gem/reo 1 and 2 year survival and median OS.
"Hey Freddy... You are posting #$%$ that has no backing. You posted fluff, as well as I have listed several legitimate sites that show a much different picture than you paint."
How about the Financial Times of London - is hat good enough backing for you? They totally agree with "The Daily Rover"
"The 5 analysts offering 12 month price targets for Oncolytics Biotech Inc. have a median target of 3.00, with a high estimate of 8.00 and a low estimate of 0.9308. The median estimate represents a 310.96 percent increase from the last price of 0.73". The Financisl Times of London does not list who the 5 analysts are - nor do I care - I'll take their word for it.
Now I guess you are going to say that you think Kenny, Armed, Bailey and myself were also picked by the Financial Times of London to do the analysis on Oncolytics. : )
Dlask - just go'gl "Oncolytics Biotech, Inc. Analyst Rating Update daily Rover". - and you will see that what I posed was an honest, accurate quote from that article. Grow up.
Hey Dlask - like I said I am just the messenger and posted the article quoting the analysts summary. You are tryng to spin it into something I said. The article is on the internet just go'gl it.
Dlask - I'm just the messenger. Historical ratings from 2013 and 2014 are meaningless now and you know it. You are spewing your book against current ratings of 5 Wall Street analysts with a combined target of $3 on a current 60 cent stock. Give it a rest.
Oncolytics Biotech, Inc. (NASDAQ:ONCY): 1 analysts have rated the shares as a strong buy. The Company shares has received a rating of Buy from 2 Wall Street Analysts. 1 analysts have rated Hold. Oncolytics Biotech, Inc. shares have received a Mean Price Target of $3.67. According to the rating issued from 5 Wall Street Analysts, the High Price Target is seen at $8 while the Lower end of the Price Target is seen at $1.87. The Median Price Target is calculated at $3.
Nome - i was a little surprised by them choosing Bladder Cancer forNeo-adjuvant. I emailed BT with the below questions - if I get a response I pos it
Choosing Bladder cancer for the neo-adjuvant was a big surprise. I looked back at the trials and could only see where there were three patients treated for this condition - were there actually more?
Regarding the BC trial I am assuming it will be randomized open label . Is this so?
We know that test will be gemcitabine, cisplatin and REOLYSIN. Will the control be the existing SOC methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC)? or maybe Gem alone? I can't see PFS or OS coming in to play in this trial if it is going to move fast.
"Say Freddy, you forgot to mention Dr Bakaii-Saabs work at OSU. You Oncy cheerleaders are funny."
Saab may well be a credible researcher but his prematuire statements on reo being next standard of care for panc (which excited a lot of us) before he actually knew made me question his research.
Glad to add levity to your day.
A vast amount of Oncy's research has been done for free with little or no cost to the company. Pactrick Lee at Dalhausie Universiy in Canada. Kevin Harrington, Hardev Pandah, Alan Melcher, Victoria Roulstone etc at Cancer Therapy Center in the UK, Leeds Hospital and Royal Marsden - they did work on head and neck and also discovered reovirus hitch-hiking on blood cells tto avoid the immune system capability which was not known three years ago. Don Morris and staff in Calgary Canada doing research on myeloma, nuroblastoma, prostate cancer, breast cancer - you can see the video on Utube - "Study investigates virus as possible treatment for multiple myeloma." - two free to the company NCI sponsored myeloma trials have been started based on their research as well as one or two of the Canadian trials. Dr. Sanjay Goel at Montefiore medical center and his research with reovirus in colorectal cancer. There is also free reovirus research being done in Tokyo on stomach cancers which are prevalent in Japan. There are a lot more researchers doing free research on reovirus, practially every week or two anotgher reovirus article comes out that was not sponsored by the company - for example lab work with reovirus and pd1, pdl1 inhibitors. Just because the company may be spending less on research - probably to preserve capital so they don't have to dilute as much (which should make investors happy) - that does not mean that research is not continuing in a big way - because a lot of researchers believe that reovirus works in killing cancer cells and priming the immune system to attack and kill cancer cells also.
No you are not an idiot you are a dreamer. And if your posting name is referring to the Boston Red Sox you know dreams can come true if you wait long enough. : )
" Oncy is not a ponzi scheme. Everything done here seems like it was perfectly legal." Glad you told Dlask that and was going to do it myself. He is basically called the company criminals ala Madoff. It's fine to criticise management performance, call them incompetent or whatever all you want but you must be careful not to cross the line with criminal accusations that are not true, that you can't support and that can come back and bite you bad if the company wants to pursue it.
"The company has never presented efficacy data for glio (KM or PFS plots) ...... one scan doesn't count. "
The FDA was impressed enough with the company's work in GLIO to give them an Orphan Drug Designation.
From the Feb 15 2015 Article "FDA Grants Reolysin Orphan Drug Designation for Ovarian Cancer":
"On February 9, 2015, Oncolytics also filed for an FDA orphan drug designation for Reolysin for the treatment of high-grade gliomas (HGG) in pediatric patients. Oncolytics has conducted three previous clinical studies in brain cancers including gliomas, and has found that Reolysin can infect a variety of brain tumors when delivered intravenously. Early clinical data suggesting that intravenously delivered Reolysin can cross the blood brain barrier and infect tumors opens up the possibility of treating a large patient group with unmet needs, specifically those with brain metastases associated with a number of cancer types,” said Thompson, in an April 2014 release."
"The company has never had any mention of bladder cancer in their presentation. It hasn't provided any data demonstrating that REO does anything in bladder."
Bladder Cancer - From the Phase 1 monotherapy 1 UK trial: Tumour Response - Metastatic bladder cancer one patient: Stable Disease at 4 months. Minor tumor response (24% tumor reduction) in metastatic lesion (lymph node); patient later reported as disease free post surgery (pPR).
In a neo-adjuvant trial you are looking for tumor shrinkage in magnitde and velocity. The name of the game is maximum shrinkage in the quickest amount of time and then have the surgery as quickly as possible. Therefore patients are in the trial for a very short time, they are not waiting for PFS and OS for many months or years - probably just 1 to 3 months. I guess the yardstick for comparison is test magnitude and velocity vrs control magnitude and velocity but not sure if that's all.
So in one sense the trial will be quick per patient. And how fast overall depends on how many centers and how many patients will be needed in test and control and how fast they can enroll. We'll know the number of sites and patients information when clinicaltrials.gov is updated. But at any rate it should be much faster than a non neo-adjuvant trial. And the company says it has enough funds now to fund this trial to completion.
Here are some rough statistics I dug up from the internet:
Appx. 70,000 new cases of bladder cancer in US per year
Appx 25% of these patients - 17,500 will eventually need to have their bladders removed
Appx. 20% of these patients - 3,500 get neo-adjuvant therapy currently and more should be getting it because there is a survival benefit when neo-adjuvant is done before surgery. Triple the number for worldwide.
The potential market is not huge but is not too shabby either if it is approved for this indication. .
Nome - your thoughts.
Neoadjuvant for bladder cancer:
MVAC remains the preferred neoadjuvant regimen. The regimen is methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and was first described in 1985 - so it has been around a long time.
MVAC tends to injure the bone marrow and cause serious infections and sometimes death.
In a series of 160 patients treated at Strong Memorial Hospital from 1999 to 2009, found that Gemcitabine and Cisplatin is a good substitute for MVAC with fewer side effects. However although this combination is used for neo-adjuvant it has never been tested in a PH III clinical trial.
Our neo-adjuvant trial will be gemcitabine, cisplatin and REOLYSIN against the SOC (I guess) MVAC. Since Gem/Cisplatin has been shown to have less side effects than MVAC one would think that adding Reo to that combination would not increase the side effects much, if any. And since Reo and Gem are synergisic (as shown in Reo017 panc trial) it seems to me that there could be a very high probability of success in this trial with tumor reduction or possible elimination prior to surgery. Additionally there is the possibility of immune identification and attack on metastatic bladder cells which metasticise to the liver, bones and other organs - even though with neo-adjuvant you are looking for the cytotoxic side of the agents not the immune aspects.
I would guess the company spent a long time and a lot of conversations with EME and FDA in coming up with this registration trial. In what I have read it seems to be an unmet need because of the following reasons:
Only 20% of the patients undergoing bladder cancer surgery get neo-adjuvant treatment (maybe because of toxicity) and for those who do get it and don't have complications there seems to be a fairly large statistical survival benefit if you have neo-adjuvant reatment prior to surgery.
So it looks like the EME and/or FDA may be looking for a safer alternaternative to MVAC
The oncolytic effects of reovirus in canine solid tumor cell lines
1) Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753–8515, Japan 2) Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi 753–8515, Japan 3) Oncolytics Biotech Inc., Calgary, Alberta, Canada 4) Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753–8515, Japan 5) Biomedical Science Center for Translational Research, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi 753–8515, Japan
Submit Released on J-STAGE 2015/06/01 [Advance Publication] Released 2015/01/16
Oncolytic virotherapy is a new strategy for cancer treatment for humans and dogs. Reovirus has been proven to be a potent oncolytic virus in human medicine. Our laboratory has previously reported that canine mast cell tumor and canine lymphoma were susceptible to reovirus. In this study, canine solid tumor cell lines (mammary gland tumor, osteosarcoma and malignant melanoma) were tested to determine their susceptibility towards reovirus. We demonstrated that reovirus induces more than 50% cell death in three canine mammary gland tumors and one canine malignant melanoma cell line. The reovirus-induced cell death occurred via the activation of caspase 3. Ras activation has been shown to be one of the important mechanisms of reovirus-susceptibility in human cancers. However, Ras activation was not related to the reovirus-susceptibility in canine solid tumor cell lines, which was similar to reports in canine mast cell tumor and canine lymphoma. The results of this study highly suggest that canine mammary gland tumor and canine malignant melanoma are also potential candidates for reovirus therapy in veterinary oncology.
This studentship aims to:
1. Investigate the role of anti-tumour immunity for the efficacy of reovirus, and its potential to eradicate early and late stage disease.
2. Examine the impact of reovirus treatment on the expression of an array of T-cell inhibitory molecules (LAG3, Tim3, PD-1) as potential therapeutic targets.
3. Enhance the development and longevity of anti-MM immunity by combining with novel immunomodulatory drugs (e.g. checkpoint inhibitors, proteasome inhibitors, monoclonal antibodies).
4. Optimise combinations with standard-of-care, particularly dexamethasone, which may impede or potentiate reovirus efficacy.
5. Inform future Leeds-led early clinical trials.
Leeds Institute of Cancer and Pathology PhD Studentships
The Leeds Institute of Cancer and Pathology has up to seven full time PhD Studentships available for home/EU students. These PhD studentships will cover academic fees at the home/EU rate together with a personal maintenance grant for up to three years (£14,000 for session 2015/16).
Professor G Cook, Dr F Errington-Mais, Dr C Parrish - Enhancing the clinical potential of Reovirus for patients with Multiple Myeloma.
Multiple myeloma (MM) is an incurable blood cancer, for which therapeutic options are often limited by comorbidity and frailty, therapy side effects and the heterogeneity of clonal tumour profiles at presentation and progression. Novel therapeutic agents, with minimal toxicity and non-overlapping mechanisms of action, are urgently needed. Extragenomic and immunotherapeutic strategies have significant potential, harnessing the host immune system to direct anti-tumour activity. One such strategy, explored in this project, is the use of oncolytic viruses.
A recent phase I dose-escalation study with single agent reovirus in myeloma demonstrated that virus can access malignant cells in the bone marrow following intravenous delivery (no dose limiting toxicities were reported) and our own studies have confirmed the direct lytic potential of reovirus in MM. However, evidence is mounting that the efficacy of virotherapy may hinge on its capacity to induce immunogenic oncolysis and consequent secondary anti-tumour immune responses. We have established that reovirus can activate innate immunity, for example enabling NK cells to kill MM cells. However, the role of reovirus-induced adaptive anti-tumour immunity remains relatively unexplored and it is imperative that we understand the biological mechanisms by which reovirus may exert its anticancer effects. Crucially, this will facilitate the rational design of combination therapies to improve patient outcomes.
Moon - I would say yes in addition to being the second reo trial using GM-CSF - the first being the pediatric brain trial in the US which according to BT will start enrolling very soon. Also as being translational/neo-adjuvant it should run quickly per patient with only a limited number of patients as they did with the UK translaional colorectal met/liver trial (only 10 patients). The question is how fast they start the trial and how fast they can enroll even a limited number of patients especially if a new SOC arises with Amgen's melanoma virus/drug. That is if Talimogene Laherparepvec gains marketing approval soon in the UK - a difficul task for sure if very expensive.