› Forums › General Melanoma Community › New Generation Immuno Therapy?
- This topic has 15 replies, 4 voices, and was last updated 9 years, 8 months ago by
RJoeyB.
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- August 8, 2014 at 8:44 am
Hello,
I was browsing the ASCO library and found this on immuno therapy…
Could this be the next generation after nivo & pembro?? Seems quite promising. Anyone here participated in any trials?
Best regards, Rick
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- August 8, 2014 at 5:00 pm
I don't have any experience with any of them, but I've been keeping tabs on these three "injectables", T-Vec, electroporation, and PV-10, for a couple of years. All are interesting and like anything, have their limits, specifically, each requires an accessible, injectable tumor/lesion. It would seem (in my opinion) that they would be best applied for patients with low tumor burden and in conjuction with another checkpoint inhibitor immunotherapy (ipi, nivo, pembro) or cytokine (IL-2 or IL-12).
Trials have been small, from what I've read. In particular, for PV-10 theyve been reporting these same trial results (for 13 total patients) for a trial that ended more than two years ago and haven't moved forward with another trial — I believe they ran into some issues with the FDA, where the company kept coming back asking for various approvals and the FDA told them, again, you have to run more trials first and stop asking for approvals without them. At the same time, it has the attention of someone at Moffitt now, which is a good thing and supposedly the company is planning to open a new trial soon.
Again, I think there's potential, not necessarily as a next-generatio immunotherapy, but as complementary options for some immunotherapies, and, perhaps in a smaller subset of patients with low tumor burden, a standalone option. Even with radiation therapy, there is anecdotal information that supports radiation of one tumor can incite an immune response at a distant tumor, and that the effect may be enhanced by existing immunotherapies. If we think of the immune system as "teachable" (which it is), then, in theory, the destruction and systemic disposal of a large number of a certain type of cells (like melanoma cells) has the potential to train the adaptive immune system to recognize these cells as "bad" and go after them as well. Some patients (self-included) even see this with vitiligo and nevi depigmentation. So with these injectables, if they can effectively destroy a small number of tumors, they too should have the potential to train the immune system, especially one that is already "amped up" by an existing immunotherapy.
Joe
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- August 9, 2014 at 2:34 am
Actually, Joe, PV10 has some new results. An international report with 28 patients was reported at ASCO this year as well as results from 8 patients enrolled in a pilot study at Moffit where all 8 had regression in the injected tumor and 4 had regression in both the injected tumor and a bystander lesion. See my May 18 blog post for details (out of town so can't attach a link…sorry). Additionally, Weber and Ribas addressed intralesional injections in their "Pretty darn impressive…" chat (see June 13 post). In my July 27 post…additional injectables are addressed…using IL2 as well as LTX 315. Just a beginning look…but still. As far as 're-firing' the immune system…I fear it is a tricky business. LAG-3 may come to be an important player. My post on June 29 talks about that and has a link to a researcher's video presentation addressing what happens once the immune system has been fired…and how to get it to mount another response! Pretty cool stuff.
best to you all. Celeste
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- August 9, 2014 at 2:57 am
Great stuff Celeste. I admit with all the summer activities I haven't been to your blog as much lately. Looks like I have some studying to do.
Like Rick I'm always on the look out for the next generation immunotherapy and found this article recently.
Seems like real promising stuff. The article doesn't specifically mention melanoma and I'm not sure if that's an oversight or for some reason melanoma does not have this checkpoint protein. I sent an email to the author for clarification but did not get a response.
Brian
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- August 9, 2014 at 2:57 am
Great stuff Celeste. I admit with all the summer activities I haven't been to your blog as much lately. Looks like I have some studying to do.
Like Rick I'm always on the look out for the next generation immunotherapy and found this article recently.
Seems like real promising stuff. The article doesn't specifically mention melanoma and I'm not sure if that's an oversight or for some reason melanoma does not have this checkpoint protein. I sent an email to the author for clarification but did not get a response.
Brian
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- August 9, 2014 at 2:57 am
Great stuff Celeste. I admit with all the summer activities I haven't been to your blog as much lately. Looks like I have some studying to do.
Like Rick I'm always on the look out for the next generation immunotherapy and found this article recently.
Seems like real promising stuff. The article doesn't specifically mention melanoma and I'm not sure if that's an oversight or for some reason melanoma does not have this checkpoint protein. I sent an email to the author for clarification but did not get a response.
Brian
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- August 9, 2014 at 11:44 am
Thank you Celeste for your very informative blog! Besides Melanoma Missionary, it has excellent information. Every melanoma patient should be following your blog and Jim's blog for current information on treatment and other important topics.
Maureen
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- August 9, 2014 at 11:44 am
Thank you Celeste for your very informative blog! Besides Melanoma Missionary, it has excellent information. Every melanoma patient should be following your blog and Jim's blog for current information on treatment and other important topics.
Maureen
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- August 9, 2014 at 11:44 am
Thank you Celeste for your very informative blog! Besides Melanoma Missionary, it has excellent information. Every melanoma patient should be following your blog and Jim's blog for current information on treatment and other important topics.
Maureen
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- August 13, 2014 at 4:47 pm
Thanks Celeste, I hadn't seen the newer PV10 results. I've been following it for a couple of years and it just seemed stagnant, then in May just before ASCO there was a bunch of back and forth between them and the FDA in the vein of what I wrote above. Regardless, it's good to see it move forward and them getting some positive results.
If one or more of these agents works out, the intralesional approach will be another good tool for a subset of patients, but probably not a revolutionary step forward as we've seen with the targeted therapies and checkpoint inhibitors. For patients with low tumor burden and accessible tumors this could be great. I think I've heard of cases where there was an accessible but, for whatever reason, unresectable tumor where one of the intralesional agents was able to eradicate that tumor.
And agreed, I think proving that a local treatment, whether radiation or an intralesional injection, helps modulate an immune response at a distant disease site is going to be difficult. There have been enough anecdotal cases of this happening that it warrants further study to truly understand the mechanism of action, but I'm far from suggesting that the approach anytime soon be, "Hey, we're going to radiate this bone met in your leg and hopefully that alone will stimulate your immune system to take care of that lung met." Taken together, though, there is some hope in a combination of local intralesional therapies complemented by systemic immunotherapies.
Joe
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- August 13, 2014 at 4:47 pm
Thanks Celeste, I hadn't seen the newer PV10 results. I've been following it for a couple of years and it just seemed stagnant, then in May just before ASCO there was a bunch of back and forth between them and the FDA in the vein of what I wrote above. Regardless, it's good to see it move forward and them getting some positive results.
If one or more of these agents works out, the intralesional approach will be another good tool for a subset of patients, but probably not a revolutionary step forward as we've seen with the targeted therapies and checkpoint inhibitors. For patients with low tumor burden and accessible tumors this could be great. I think I've heard of cases where there was an accessible but, for whatever reason, unresectable tumor where one of the intralesional agents was able to eradicate that tumor.
And agreed, I think proving that a local treatment, whether radiation or an intralesional injection, helps modulate an immune response at a distant disease site is going to be difficult. There have been enough anecdotal cases of this happening that it warrants further study to truly understand the mechanism of action, but I'm far from suggesting that the approach anytime soon be, "Hey, we're going to radiate this bone met in your leg and hopefully that alone will stimulate your immune system to take care of that lung met." Taken together, though, there is some hope in a combination of local intralesional therapies complemented by systemic immunotherapies.
Joe
-
- August 13, 2014 at 4:47 pm
Thanks Celeste, I hadn't seen the newer PV10 results. I've been following it for a couple of years and it just seemed stagnant, then in May just before ASCO there was a bunch of back and forth between them and the FDA in the vein of what I wrote above. Regardless, it's good to see it move forward and them getting some positive results.
If one or more of these agents works out, the intralesional approach will be another good tool for a subset of patients, but probably not a revolutionary step forward as we've seen with the targeted therapies and checkpoint inhibitors. For patients with low tumor burden and accessible tumors this could be great. I think I've heard of cases where there was an accessible but, for whatever reason, unresectable tumor where one of the intralesional agents was able to eradicate that tumor.
And agreed, I think proving that a local treatment, whether radiation or an intralesional injection, helps modulate an immune response at a distant disease site is going to be difficult. There have been enough anecdotal cases of this happening that it warrants further study to truly understand the mechanism of action, but I'm far from suggesting that the approach anytime soon be, "Hey, we're going to radiate this bone met in your leg and hopefully that alone will stimulate your immune system to take care of that lung met." Taken together, though, there is some hope in a combination of local intralesional therapies complemented by systemic immunotherapies.
Joe
-
- August 9, 2014 at 2:34 am
Actually, Joe, PV10 has some new results. An international report with 28 patients was reported at ASCO this year as well as results from 8 patients enrolled in a pilot study at Moffit where all 8 had regression in the injected tumor and 4 had regression in both the injected tumor and a bystander lesion. See my May 18 blog post for details (out of town so can't attach a link…sorry). Additionally, Weber and Ribas addressed intralesional injections in their "Pretty darn impressive…" chat (see June 13 post). In my July 27 post…additional injectables are addressed…using IL2 as well as LTX 315. Just a beginning look…but still. As far as 're-firing' the immune system…I fear it is a tricky business. LAG-3 may come to be an important player. My post on June 29 talks about that and has a link to a researcher's video presentation addressing what happens once the immune system has been fired…and how to get it to mount another response! Pretty cool stuff.
best to you all. Celeste
-
- August 9, 2014 at 2:34 am
Actually, Joe, PV10 has some new results. An international report with 28 patients was reported at ASCO this year as well as results from 8 patients enrolled in a pilot study at Moffit where all 8 had regression in the injected tumor and 4 had regression in both the injected tumor and a bystander lesion. See my May 18 blog post for details (out of town so can't attach a link…sorry). Additionally, Weber and Ribas addressed intralesional injections in their "Pretty darn impressive…" chat (see June 13 post). In my July 27 post…additional injectables are addressed…using IL2 as well as LTX 315. Just a beginning look…but still. As far as 're-firing' the immune system…I fear it is a tricky business. LAG-3 may come to be an important player. My post on June 29 talks about that and has a link to a researcher's video presentation addressing what happens once the immune system has been fired…and how to get it to mount another response! Pretty cool stuff.
best to you all. Celeste
-
- August 8, 2014 at 5:00 pm
I don't have any experience with any of them, but I've been keeping tabs on these three "injectables", T-Vec, electroporation, and PV-10, for a couple of years. All are interesting and like anything, have their limits, specifically, each requires an accessible, injectable tumor/lesion. It would seem (in my opinion) that they would be best applied for patients with low tumor burden and in conjuction with another checkpoint inhibitor immunotherapy (ipi, nivo, pembro) or cytokine (IL-2 or IL-12).
Trials have been small, from what I've read. In particular, for PV-10 theyve been reporting these same trial results (for 13 total patients) for a trial that ended more than two years ago and haven't moved forward with another trial — I believe they ran into some issues with the FDA, where the company kept coming back asking for various approvals and the FDA told them, again, you have to run more trials first and stop asking for approvals without them. At the same time, it has the attention of someone at Moffitt now, which is a good thing and supposedly the company is planning to open a new trial soon.
Again, I think there's potential, not necessarily as a next-generatio immunotherapy, but as complementary options for some immunotherapies, and, perhaps in a smaller subset of patients with low tumor burden, a standalone option. Even with radiation therapy, there is anecdotal information that supports radiation of one tumor can incite an immune response at a distant tumor, and that the effect may be enhanced by existing immunotherapies. If we think of the immune system as "teachable" (which it is), then, in theory, the destruction and systemic disposal of a large number of a certain type of cells (like melanoma cells) has the potential to train the adaptive immune system to recognize these cells as "bad" and go after them as well. Some patients (self-included) even see this with vitiligo and nevi depigmentation. So with these injectables, if they can effectively destroy a small number of tumors, they too should have the potential to train the immune system, especially one that is already "amped up" by an existing immunotherapy.
Joe
-
- August 8, 2014 at 5:00 pm
I don't have any experience with any of them, but I've been keeping tabs on these three "injectables", T-Vec, electroporation, and PV-10, for a couple of years. All are interesting and like anything, have their limits, specifically, each requires an accessible, injectable tumor/lesion. It would seem (in my opinion) that they would be best applied for patients with low tumor burden and in conjuction with another checkpoint inhibitor immunotherapy (ipi, nivo, pembro) or cytokine (IL-2 or IL-12).
Trials have been small, from what I've read. In particular, for PV-10 theyve been reporting these same trial results (for 13 total patients) for a trial that ended more than two years ago and haven't moved forward with another trial — I believe they ran into some issues with the FDA, where the company kept coming back asking for various approvals and the FDA told them, again, you have to run more trials first and stop asking for approvals without them. At the same time, it has the attention of someone at Moffitt now, which is a good thing and supposedly the company is planning to open a new trial soon.
Again, I think there's potential, not necessarily as a next-generatio immunotherapy, but as complementary options for some immunotherapies, and, perhaps in a smaller subset of patients with low tumor burden, a standalone option. Even with radiation therapy, there is anecdotal information that supports radiation of one tumor can incite an immune response at a distant tumor, and that the effect may be enhanced by existing immunotherapies. If we think of the immune system as "teachable" (which it is), then, in theory, the destruction and systemic disposal of a large number of a certain type of cells (like melanoma cells) has the potential to train the adaptive immune system to recognize these cells as "bad" and go after them as well. Some patients (self-included) even see this with vitiligo and nevi depigmentation. So with these injectables, if they can effectively destroy a small number of tumors, they too should have the potential to train the immune system, especially one that is already "amped up" by an existing immunotherapy.
Joe
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