vaccines - 1262080

The news on Stimuvax was the START trial, which we covered here. It was essentially negative, though a subset of patients who received concurrent chemo and radiation had a longer median overall survival with Stimuvax than without it. I had heard that the company may be inclined to do a follow up randomized phase III trial just in patients with received concurrent chemo/radiation for stage III NSCLC, but I haven't heard anything about it in the last 6 months.

The STOP trial with Lucanix was started in 2008 and stopped enrolling in 2012. I would have expected to hear results long before now, which I presume is a bad thing. I must confess I'm not very optimistic that Lucanix will turn out to be a significant winner.

-Dr. West

Thanks, keep it coming. xoxo

Thanks for that information -- very helpful.

It's certainly provocative to see one or more subsets of patients identified as seeming to have clinically significant benefit from the treatment. A difference of 7 months in those treated within 12 weeks of completion of prior chemotherapy is certainly in the realm of clinically significant. As a caveat, however, it's important to remember that this wasn't a prospectively identified idea, but rather that the analysis sifted through the wreckage of a negative trial and then looked at results from every angle they could think of, then focused on the ones that happened to look best. Identifying the outliers that were best is a fair principle for refining the principle and re-asking the question, so I think it makes sense to pursue this concept in further research. We just can't view results that were derived by cherry-picking through a bunch of analyses until some positive results were identified is the same as coming up with a premise and then seeing the results come out that way based on prospective study. But there are definitely some very promising leads to follow, and this is not simply a negative trial with nothing more to say about it.

Again, thanks for that helpful information.

-Dr. West

I agree that there may well be subgroups that have been overlooked in trials just called negative in the past.

However, my sense from the information provided was that the FDA left open the door to a new trial focused only on patients who received Lucanix within 12 months of prior chemo, or after chemo and radiation. In truth, I'd have to say that this first STOP trial was a very sloppily done trial that aggregated a lot of patients who shouldn't have been included together in the same trial. Patients with stage III NSCLC for which the standard of care is chemo/radiation shouldn't be included on the same trial as patients with stage IV NSCLC. It's not surprising that a trial that cut corners and put such a hodge podge of different patients into it emerged with uninterpretable results.

The point, which is bad news, actually, is that a new trial will now take another 4-5 years, I suspect, to be completed and produce a clearer answer to determine whether Lucanix will provide a significant benefit in a more refined population. The company may or may not elect to do such a trial now, given the commitment of time and money, but we won't have any practice-changing new information in the next year or two.

-Dr. West

Dr. West, Lucanix seemed to help some patients that were in good health and in remission/close to remission. Perhaps the responder-after-chemo subset were among those who responded as Lucanix kicked the cancer that was lying on the boxing canvas. Perhaps the reasons also lie in the type of responding cancer cell that had certain molecular and metabolic features (which we at this point scientically are not aware of) which made it responsive - as opposed to the 12 months of chemo having "staying power" for some patients who were particularly responsive to the chemo. It seemed that Lucanix had some impressive results in some cases that shouldn't have allowed it to become completely dead in the water. Unfortunately, it seems like the research efforts almost killed NovaRx.. I just hope that exceptional cases and compassionate use parameters may be used in applicable cases while we wait another 4-5 years.

It is like we have come to know well. Research outcomes can make us eager and then pull the rug from under us.It feels like waiting for the Queen Mary to make a U-turn in the Panama Canal.

I agree with all of the perhaps statements. That's not definite, and I don't think NovaRx can sustain itself on compassionate use cases. It needs to do the study it should have done originally: look at a better defined population of either stage III patients after chemo/radiation or stage IV patients, both randomized within 12 weeks of completion of prior chemotherapy, and randomize them to Lucanix or placebo. I agree that the research efforts have put NovaRx on life support, but that is largely because they designed and conducted their trial rather poorly.

-Dr. West

So the failure of Lucanix may be more a product of the study design and flaws, as opposed to the drug's therapeutic potential or lack thereof.

I think the subgroup analysis is promising, and it may well be real. But I think that the results available so far are not enough to say we should be using Lucanix to treat lung cancer now. Instead, they say that this isn't just a negative trial, but rather that it would be valuable to do another trial to specifically focus on the patients who seemed to get the most benefit in the trial that has already been completed. If a subsequent trial shows a benefit that is significant in the newer trial, it should lead to a change in clinical practice.

-Dr. West

I know that blogging with LC patients can be challenging, as we are very eager to get new treatment tools put into practice due to the lack of such tools at present. The responder group is close to 60% of research subjects involved in phase III. I share the feelings of ssfxl. We wish analyses of the data at hand can take a drug with a less imposing side effect profile like Lucanix and see a place in lieu of heavy volume response group. The issue about vaccines and immunotherapy is conceptually they should work on patients who are healthier to the point they can take advantage of their immunity and the lesser burden conditions of the cancer in some cases. Also, time seems to be a necessary tool to get the response mechanisms in a viable position. The issue has been addressed as to whether or not there is better potential in earlier stages of cancer or NED/near NED conditions. Wish there was a way to build a better mouse trap here.

Here is just a few more thoughts, and then I should sit back. The data on Lucanix has been a product of years of work. When I look at the enthusiasm seen with immunotherapy agents such as MK-3475, I realize that this drug has not been studied as long, and like other immunotherapy agents is not getting very strong response rates. I am glad that the research in this arena is opening and growing, but in comparison the Lucanix data does not like a drug that is failing and keep trudging on "the long march". Personally, with a 20 month good solo run and Tarceva and then another good response with Tarceva and Alimta, I would seriously look at participating in a Lucanix study when this current treatment begins to falter as I have been quite fortunate to have a low tumor load. I still think that this drug may have a viable place, even though it is running the hurdles instead of a dash. I hope that a bigger company may take in jointly or separately the mechanisms to explore for a place for Lucanix. I will now try to be quiet.y

Error in grammar midway through last post- ... the Lucanix data does not look like a drug that is failing but rather keeps trudging "the long march" after a phase III.

And it is known that drug companies - like those working on new immunotherapy agents - work hard on study design for phases I and II to paint a good picture on efficacy and tolerability.

Now I will sit down.

We'll need to see where it goes from here. The biggest problem, I think, is that many smaller companies have one good shot on goal, given the cost of running large clinical trials. I don't know if NovaRx will be able to run another trial, but perhaps, given the promising leads in the subgroups, they'll partner or be bought by a larger company that can follow up with a trial in one or more of the subgroups that looked promising in the STOP trial.

-Dr. West

The new stimuvax (tecemotide, BLP25) trial will be opening at our center and many others within the next 1-3 months (called START2). It is going to be a large international trial with 1002 patients, focusing only on the concurrent chemotherapy + radiation patients. My understanding is that Dr Mok has a similar large trial ongoing in Asia (INSPIRE). So Stimuvax is not out of the running yet.

Thanks Dr. Creelan for swooping in with that excellent piece of info.