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Phase 1 antibody drug conjugate trial? Thoughts?
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Phase 1 antibody drug conjugate trial? Thoughts?

› Forums › General Melanoma Community › Phase 1 antibody drug conjugate trial? Thoughts?

  • Post
    • February 28, 2013 at 7:32 pm
    awillett1991
    Participant
      I’m researching Genentech trial this for a friend. It’s a small phase 1 trial, side effects sound NASTY because of the MMAE, from what I can understand. Have any of you gurus out there heard anything or have any thoughts I’d really appreciate it.. This is his only option left because of the issues he has.

      Thanks!

      I’m researching Genentech trial this for a friend. It’s a small phase 1 trial, side effects sound NASTY because of the MMAE, from what I can understand. Have any of you gurus out there heard anything or have any thoughts I’d really appreciate it.. This is his only option left because of the issues he has.

      Thanks!

    Viewing 5 reply threads
    • Replies
        • February 28, 2013 at 7:34 pm
        awillett1991
        Participant
          • February 28, 2013 at 7:34 pm
          awillett1991
          Participant
            • February 28, 2013 at 7:34 pm
            awillett1991
            Participant
              • February 28, 2013 at 8:29 pm
              POW
              Participant

                No, I never heard of that before. Sorry. However,  did poke around about it a bit. 

                From what I can gather, monomethly auristatin E (MMAE) is a toxin. When it is attached to an antibody, it is not toxic in the blood stream. However, when the antibody/MMAE complex is taken into a cell, the toxin becomes active and kills the cell. 

                To make the toxin most effective against different types of cancer, the company that makes it (Celledex) has attached the toxin to different, specific antibodies. So, for example, in 2008 they attached MMAE to an antibody that binds to lymphona cells and got a pretty good response in terms of killing lymphona–that complex is now FDA approved. Then in 2010 they attached MMAE to an antibody that binds to breast cancer cells, but that didn't work so good–the company never did publish their final data. Apparently, the company is now trying MMAE attached to an anti-melanoma antibody (which one I don't know) as well as trying prostate cancer, non-Hodgkin lymphona and some others. 

                As for side effects, the worst ones seem to be neutropenia (killing white blood cells) and neuropathy (killing peripheral nerve cells) plus the usual nausea, fever, etc. If a lot of antibody molecules bind strongly to the melanoma cells, the MMAE will probably be pretty effective. If not many antibody molecules bind, or if they only bind weakly, the complex probably won't work. And, of course, the amount of antibody bound may well vary from person to person. 

                I hope this helps your friend decide.

                  • February 28, 2013 at 8:45 pm
                  awillett1991
                  Participant
                    Yes that’s about what I found too. It’s at Sarah Cannon Cancer Center so I gave him some questions to ask. They already told him its a type of fancy chemo basically, that goes after only the melanoma cells (if it works) and he would have to keep taking it forever.

                    He’s had a good long life, been fighting stage 4 mucosal and suffering through it almost 2 years. I’m not sure if he’ll do it or not. At best they’ve seen stable disease 4-6 mos. but at what price. Sigh. The choices we have to make.

                    Thank you,
                    Amy

                    • February 28, 2013 at 8:45 pm
                    awillett1991
                    Participant
                      Yes that’s about what I found too. It’s at Sarah Cannon Cancer Center so I gave him some questions to ask. They already told him its a type of fancy chemo basically, that goes after only the melanoma cells (if it works) and he would have to keep taking it forever.

                      He’s had a good long life, been fighting stage 4 mucosal and suffering through it almost 2 years. I’m not sure if he’ll do it or not. At best they’ve seen stable disease 4-6 mos. but at what price. Sigh. The choices we have to make.

                      Thank you,
                      Amy

                      • February 28, 2013 at 8:45 pm
                      awillett1991
                      Participant
                        Yes that’s about what I found too. It’s at Sarah Cannon Cancer Center so I gave him some questions to ask. They already told him its a type of fancy chemo basically, that goes after only the melanoma cells (if it works) and he would have to keep taking it forever.

                        He’s had a good long life, been fighting stage 4 mucosal and suffering through it almost 2 years. I’m not sure if he’ll do it or not. At best they’ve seen stable disease 4-6 mos. but at what price. Sigh. The choices we have to make.

                        Thank you,
                        Amy

                      • February 28, 2013 at 8:29 pm
                      POW
                      Participant

                        No, I never heard of that before. Sorry. However,  did poke around about it a bit. 

                        From what I can gather, monomethly auristatin E (MMAE) is a toxin. When it is attached to an antibody, it is not toxic in the blood stream. However, when the antibody/MMAE complex is taken into a cell, the toxin becomes active and kills the cell. 

                        To make the toxin most effective against different types of cancer, the company that makes it (Celledex) has attached the toxin to different, specific antibodies. So, for example, in 2008 they attached MMAE to an antibody that binds to lymphona cells and got a pretty good response in terms of killing lymphona–that complex is now FDA approved. Then in 2010 they attached MMAE to an antibody that binds to breast cancer cells, but that didn't work so good–the company never did publish their final data. Apparently, the company is now trying MMAE attached to an anti-melanoma antibody (which one I don't know) as well as trying prostate cancer, non-Hodgkin lymphona and some others. 

                        As for side effects, the worst ones seem to be neutropenia (killing white blood cells) and neuropathy (killing peripheral nerve cells) plus the usual nausea, fever, etc. If a lot of antibody molecules bind strongly to the melanoma cells, the MMAE will probably be pretty effective. If not many antibody molecules bind, or if they only bind weakly, the complex probably won't work. And, of course, the amount of antibody bound may well vary from person to person. 

                        I hope this helps your friend decide.

                        • February 28, 2013 at 8:29 pm
                        POW
                        Participant

                          No, I never heard of that before. Sorry. However,  did poke around about it a bit. 

                          From what I can gather, monomethly auristatin E (MMAE) is a toxin. When it is attached to an antibody, it is not toxic in the blood stream. However, when the antibody/MMAE complex is taken into a cell, the toxin becomes active and kills the cell. 

                          To make the toxin most effective against different types of cancer, the company that makes it (Celledex) has attached the toxin to different, specific antibodies. So, for example, in 2008 they attached MMAE to an antibody that binds to lymphona cells and got a pretty good response in terms of killing lymphona–that complex is now FDA approved. Then in 2010 they attached MMAE to an antibody that binds to breast cancer cells, but that didn't work so good–the company never did publish their final data. Apparently, the company is now trying MMAE attached to an anti-melanoma antibody (which one I don't know) as well as trying prostate cancer, non-Hodgkin lymphona and some others. 

                          As for side effects, the worst ones seem to be neutropenia (killing white blood cells) and neuropathy (killing peripheral nerve cells) plus the usual nausea, fever, etc. If a lot of antibody molecules bind strongly to the melanoma cells, the MMAE will probably be pretty effective. If not many antibody molecules bind, or if they only bind weakly, the complex probably won't work. And, of course, the amount of antibody bound may well vary from person to person. 

                          I hope this helps your friend decide.

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