Seth M. Pollack, MD, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division, Assistant Professor, University of Washington, Division of Oncology talks about clinical trials for a vaccination that could help patients fight sarcoma.
Interview conducted by Ivanhoe Broadcast News in October 2017.
Phase I of the CMB drug is over tell me how that went, what happened?
Dr. Pollack: Right. The Phase I of LB305 went really well. Phase I was a dose escalation trial and we treated the first patients ever with this totally new type of vaccine. This vaccine reprograms the cells in the immune system that tell the immune system how to fight cancer. And the drug was safe and patients did seem to be living longer than we would have expected.
One thing Tiffany was emphatic about is after somebody who has a chemo is that the side effects were pretty much nil for her.
Dr. Pollack: Yeah, no patient has had bad side effects. Some patients have had some mild fevers, some fatigue the day after the injection but for no patient has the fatigue been bad enough that say they couldn’t go to work or do something important to them.
How then from the Phase I, since it was successful what then did the Phase II consist of and where did they get CMB from?
Dr. Pollack: Phase I tested this unique type of vaccine that can reprogram the immune system to fight cancer. In the Phase II, they added a boost to the vaccine so that not only would the reprogrammed immune system fight the cancer, but an extra dose of the cancer target would be injected into the patients to get a little more “humph” to the vaccine. And the results seem to be good as well, patients again are living longer than we would expect for patients with such difficult-to-treat diseases.
When you say longer can that be calculated or how are you calculating that?
Dr. Pollack: We’ve been following the patients for a long time and we actually still don’t have the average overall survival number because patients seem to be doing so well. But it seems to be at least in the ballpark of patients who have been on trials of other FDA-approved drugs.
So months, years, hard to say?
Dr. Pollack: Well the average overall survival hasn’t been reached on the Phase II trial.
The drug starts with an A, it’s an add-on drug right? Is that why it’s CMB because it’s Phase II?
Dr. Pollack: No. In the first trial, the trial was testing just this vaccine, the vector that reprograms the immune system. Then there was a follow up Phase I sort of Phase I/ Phase II trial. It was really a Phase I trial but with an extended cohort of patients to really look at the clinical outcomes. In that trial, that’s where we combined a vaccine plus this boosting shot. The boosting shot consisted of the tumor target plus an extra medicine to make the immune system come and recognize that tumor target. Most recently there’s been a randomized Phase II trial that combined this CMB regiment, the vaccine plus the booster, with a drug that locks an immune check point. And that’s called Texalizamab. Those results we’re still waiting for the final results. There was a snapshot of those results presented at the European Society Medical Oncology ESMO. And it looks like the combination might be better but we still have to wait and see. We have to see the follow up results for that.
Is that part of Phase II as well, is that another arm of Phase II?
Dr. Pollack: That’s a new Phase II study. So there was a Phase I, then there was a Phase I but a little bit more of an expanded Phase I and then there was this Phase II.
Explain to me how the drug reprograms the cells?
Dr. Pollack: This is a totally new type of vaccine using a kind of virus that’s never been used before in vaccine studies. It’s a therapeutic vaccine. That means that it’s being used to treat patients who already have cancer, not to prevent cancer. There are cells in the immune system called dandretic cells. Those cells tell T-cells what they should be fighting. This vaccine specifically goes to those dandretic cells and tells them to fight the cancer which in turn tell the T-cells to fight the cancer
So it’s kind of a conversation rather than going through the T-cells then?
Dr. Pollack: Right, so most immunotherapies to date have worked directly on the T-cells. And that makes sense because the T-cells are the cells that actually fight the cancer. This vaccine works by reprogramming the cells that tell the T-cells what to do.
Let’s talk a little bit about Tiffany and how she did with this trial because the way she described it she was pretty miserable coming into the trial.
Dr. Pollack: Yeah, Tiffany had a really bad disease. She had been on a lot of different treatments. She had multiple surgeries, radiation, a lot of different types of chemo and she was pretty worn out. Some of the types of chemo that are most effective against synovial sarcoma were very toxic. They made it so that she couldn’t work, that she wasn’t able to do the things that she needed to do to take care of her family with three kids. She was pretty worn out by the time she started considering this trial.
What kind of a difference did it make in her life?
Dr. Pollack: The vaccine didn’t cause really any side effects for Tiffany, no significant side effects. At first it just stabilized the tumor. Her tumor had been growing and had been growing steadily and at first it just sort of slowed the growth of the cancer down to the point where it wasn’t growing a lot any more. And then things started to shrink and they didn’t start to really shrink until about a year after the vaccination. And that’s when things really started to shrink and now she’s had over eighty percent of her tumor shrink away and she’s over three years out from her vaccination.
And that is the beauty of immunotherapy right, I mean she’s hasn’t gotten a treatment in a long time.
Dr. Pollack: One of the great things about immunotherapy is that the results can be very durable and that’s something that I think has really been good for people
What’s your hope for this now that you’re finished with the trials?
Dr. Pollack: I think a lot of people are thinking that this vaccine will ultimately be evaluated in Phase III and that we’ll have a chance to really prove that it works better than some standard of care types of treatment. I think that as we go further, this vaccine will be combined with even more different kinds of immunotherapy and we’ll be able to give even more patients the kind of response that Tiffany had.
Specifically sarcoma or other types of cancer as well?
Dr. Pollack: We want to make it work better for sarcoma patients for sure. The specific cancer target that this vaccine is directing the immune system to go after is at really high levels in certain sarcoma types. But it’s also found in a minority of patients with breast cancer, lung cancer, ovarian cancer and many, many other kinds of cancer. So I think that sarcoma is a great place to prove the principle but once that principle is proven we’ll be able to expand this to treat a lot of different cancer patients.
Now you guys crunch all the data then do you go to the FDA or are you going into a Phase III?
Dr. Pollack: Right now I think I told you there was a Phase I trial then there was kind of a second bigger Phase I trial and then there was the Phase II trial. Right now we’re kind of finishing up the first Phase I trial, crunching that one up. And I think it won’t be too long before the second Phase I data gets crunched.
And then the Phase II data?
Dr. Pollack: The Phase II data needs a little bit more time to cook. Because what you need to have happen is you need to have a certain number of patients have events. They need to either progress or they need to succumb to the disease. And you need to have enough so that you can say that in the Phase II it was a randomized Phase II so you need people to say that either one arm was better or that you’ve seen enough that there’s no difference.
So really the longer we wait for Phase II results come in the better because it means people are living longer.
Dr. Pollack: Maybe, maybe. I think a lot of people are very excited about the drug and would like to see a Phase III trial and I think that that’s where things are right now.
END OF INTERVIEW
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