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Elios Therapeutics Phase IIb trial results

Elios Therapeutics Phase IIb trial results

Posted By
2/7/2020 10:29pm
Replies: 6

AUSTIN, Texas, Feb. 7, 2020 /PRNewswire/ -- Elios Therapeutics, a biopharmaceutical company developing innovative personalized therapeutic cancer vaccines, today announced that the Company presented a subgroup analysis of the prospective, randomized, double-blind, placebo-controlled Phase IIb clinical trial evaluating its personalized tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine, in patients with Stage III and IV resected melanoma.

In the study, 144 participants were randomized to receive either the vaccine or placebo to prevent recurrence. The vaccines were initiated within three months of completion of standard of care therapy at 0, 1, 2, 6, 12, and 18 months. The protocol was amended to allow concurrent treatment with checkpoint inhibitors once approved for the adjuvant setting. The primary endpoint was 24-month disease-free survival (DFS). This pre-specified sub-group analysis examined efficacy by stage, immunotherapy, and checkpoint inhibition. The analysis was performed on the intent-to-treat (ITT) population and per treatment (PT) population, which included all patients who completed the primary TLPLDC or placebo vaccine series at six months.

In the PT analysis, 24-month DFS improved among Stage IV patients in the TLPLDC vaccine group compared to placebo (73.0% vs. 0%; p=0.002) representing a statistically significant and clinically meaningful reduction in the relative risk of disease recurrence for these patients. An improvement was also seen in the ITT analysis (43.0% vs. 0%; p=0.098). Stage IV patients were more likely to receive checkpoint inhibitor therapy (50% vs. 26%, p=0.003). At the 24-month assessment, a difference in DFS between the vaccine and placebo arms was not observed in Stage III patients. Patients with Stage III disease often take longer to experience a recurrence than patients with Stage IV disease, therefore a 36-month assessment of DFS will determine the effect of treatment in this population.

While all this sounds well and good....and LORD knows, I hope this vaccine will be the CURE!!!!! We have to approach this with a full understanding what is and isn't noted in this report.

1. "The vaccines were initiated within three months of completion of standard of care therapy...." Well. That right there is a HUGE complication. First of all, that "standard of care therapy" is not defined. Further, I am a Stage IV melanoma patient, post treatment with surgery, radiation, and nivo. I remain NED for melanoma since all three of those were done in 2010. So had I had the vaccine - I would be aces, right? My point is, response to "standard of care therapy" is highly variable and hard to measure in and of itself. Given that variability and the fact that Stage IV patients have really only had access to these drugs since 2011 and Stage III patients only since 2017, determining the impact of this vaccine is hard indeed.

2. What is not included in this report (put out by the company making this vaccine FYI!!!!) - but is in a fuller reading of the result, and I quote - "Additionally, while not statistically significant, due to the sample size, a clinically meaningful improvement in 24 month DFS was observed between patients receiving the vaccine in combination with standard of care checkpoint inhibitors vs checkpoint inhibitors alone." In other words, there was no significant improvement in patients who were given standard of care checkpoint inhibitors and the vaccine vs those who got the checkpoint inhibitors alone. Meaning - the vaccine did NOT help!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

3. This is the very massaging of data that I was YELLING about here:

4. It is also what James Allison (at least to my mind) is fed up with here:

5. Here's a link to that actual abstract:

The results section reads: "144 pts were randomized (103 TLPLDC, 41 placebo); 98 pts (66 TLPLDC, 32 placebo) completed the PVS. There were no clinicopathologic differences between treatment groups. There was no difference in 24mo DFS in stage III pts (n = 112), but in stage IV pts (n = 32), the 24mo DFS was 44% vs 0% (TLPLDC vs placebo) (p = 0.41) in ITT and 73.3% vs. 0% (HR 0.14, p = 0.002) in PT. Stage IV pts were more likely to receive CPI than stage III pts (50% vs. 30%, p = 0.003). There was no difference in 24mo DFS for pts who did not receive CPI (n = 102), but in pts who received CPI (n = 42), the 24mo DFS was 49.3% vs. 31.3% (p = 0.71) in ITT and 68.8% vs. 41.7% (HR 0.46, p = 0.28) in PT, showing a trend toward improved DFS in pts who completed the PVS and received CPI (n = 31). Overall, the 36mo estimated DFS was 34.2% vs. 21.6% (p = 0.89) for ITT and 56.9% vs. 27.9% (p = 0.021) for PT.

FYI - important point to note in reading this gobble-de-gook is that a p value of anything greater than 0.05 means that the result is NOT significant!!! Think about that when you wind your way through these numbers!!! Basically, to get the numbers here that are significant and have a p value of less than 0.05 - they dropped 50 poor ratties out of the group!!! Then there's all the interesting word games they play, but ain't nobody got time for that!!!

6. I am a firm believer in vaccines. I have spent my adult life vaccinating folks and advocating for getting vaccines. I looked at a vaccine trial run by Sosman out of Vandy (at that time) in 2003 when I was first diagnosed with Stage IIIb melanoma. It didn't sound promising to me and for that and many other reasons at that point in my life I declined participation. It was a good decision as it was rapidly disbanded. I actually sought the nivo trial I did participate in from December 2010 - June 2013 because peptide vaccines were involved. FYI - they hurt like a mother, left granulomatous scars in my thighs to this day and they didn't do a damn thing! And y'all know I tell it like it is - cause here's that report from 2013: But, the heart wants what it wants and I still believe there WILL be a place for vaccines in melanoma therapy, so I have followed such things rather closely. In that vein, if you are ready for a rollicking ramble - here is a report on several vaccines and a pretty interesting history of this very vaccine along with the company and players that make it from 2018:

7. To the anon who posted this - If you are a person with melanoma or caring for a dear one with melanoma, thanks for posting this. Folks can take what I have to say about it as they wish. I think I've represented my perspective well and I prefer that things get hashed out here so that folks can know what's really behind the curtain and either pass it by or sign up for it if they think it is right for them. If however, my dear anon, you are a person from Elios - I hope you rot, cause this is not YOUR forum.

Okay. I can think of a lot more. But that's probably more than enough. - celeste

Anonymous - (2/9/2020 - 5:05am)

I'm not from Elios. My loved one failed opdivo so I am hoping for new options.
Thanks for sharing your analysis.
I think the part that is confusing to me, if I understand it correctly, is that they are saying 74% of the stage four patients did not have the cancer progress after two years? From what I understand, the immunotherapies and targeted therapies usually get about a 40% rate. So it is strange they are saying there was not difference between those two groups. Although maybe they were including the stage three people in there.

I am sorry that you and your dear one are dealing with continued melanoma despite Opdivo.

Yes - the first two things I look at when I look at data presented on a treatment option are:
1. Who is putting this out? If it is the company making the drug or an investment firm then I am skeptical from the start. Doesn't necessarily mean what they are saying isn't true - it could be spot on and fabulous. But, it could also be presented with the best possible slant in order to woo investors etc.
2. How many times do I have to ask myself, "Now, what????" - in order to understand the data presented. If you have to do that a couple times in order to believe their 1 + 1 = 2, then there might be some fuzzy math at play. Common sense is good stuff!!!

To answer your question, to the best of MY ability, is are on the right track. Here is what I wrote about this data (in a preliminary stage) when it was presented at ASCO in 2018:

"...let's get back to the TLPLDC vaccine and data touted in the ASCO piece...

This particular report appears to be based on the preliminary results from the clinical trial using TLPLDC. Here 120 Stage III/IV melanoma patients with resected tumor (ie NED) were divided into 2 groups. 83 were given the dendritic vaccine. 37 were given placebo. An interesting point is that these peeps were 3:1 :: Stage III:Stage IV. Stage III is not defined, so we could be looking at mostly Stage 3a patients who have a fairly good prognosis without any further treatment - just say'n! There was no difference in recurrence in either group at a median f/u of almost one year. The report also notes that of the patients treated, "there was a trend toward decreased recurrences in the TLPLDC arm at a median f/u of 12.6 mos." Don't forget! This is the very group from which those who recurred in the first 6 months of treatment were EXCLUDED and with that, all you got was a "trend"???!!! Now, you could possibly argue that one needs 6 months to give the vaccine a chance to work. But 6 months in melanoma world is a long time, y'all!!!"

So between the exclusion of people who did recur, combining Stage IV folks with Stage III folks - you get a bunch of meaningless mess and even if you and your drug may be respectively, someone with integrity and something of value - you have now painted all of it in a very bad light.

To more important things for you ~ your dear one and finding an effective treatment plan. There are many smart peeps here. If you wanted, you could put a bit of your dear one's history up and you may be referenced a great many effective treatment options as well as loads of support. Up to you. There are many viable treatment options beyond Opdivo these days. I hope your dear one finds an option that works for them. I wish you my best. Celeste

Hi Anon, not trying to direct you one way or another but here is a link to one of the big US hospitals and the list of trials on there home page for melanoma. They have more programs, this is just a sample and ones that stick out to me are Lag-3, NKTR-214, TLR-9, OX-40 and TiL's (Adoptive cell therapy) also of interest is OXPHOS a new program that Dr. Davies of MD Anderson talks about at the 34:00 min mark of the following video and the drug is called IACS-010759 (very early days with this one). Good luck with your research!!! Ed

So if you now compare with another leading hospital in LA you will see some similar trials but also new ones, due to the fact that different hospital have different ties to big pharma and each melanoma specialist has research interest and might have ties to the pharma companies (I am getting in the weeds sorry!) point is that many of these hospitals are offering trials that they are invested in and believe to be the next best thing. Following good science as Bubbles has been talking about means different things to different folks from what I have witnessed over the years from following new trials and new drugs they don't always get things right, think IDO inhibitor plus pembro trial that was rushed to stage 3 and totally bombed. If you look at Dr. Omid Hamid at the Angeles clinic you will see they are connected to programs that feature, Sting Agonist, IMC gp 100, intratumoral injections of different drugs, Tim-3, Gitr and a Til's program from Iovance LN-144 where they send out tumor to Iovance lab to turn into til's to be put back into patients. Until the trials run there coarse it is impossible to know what will work, as patients we have to hope that the trial that is being offered has an underlying principal that makes sense to the situation that we are in. This is where you have to have trust in the Oncologist and what they are offering. Good luck!!!Ed

Ed makes some very good points. My take is that as patients - we can only:
1. Use therapies that have come out with the best data and that are most proven. Of course that gets harder and harder when we have to start looking at trials.
2. Find a melanoma specialist you trust - especially important when you are in need of something beyond standard therapy.
3. And after all that is said and done - go with what feels right and best for you.