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Lag-3 data starting to come in and combination of Lag-3+Nivo shows great PFS

Forums General Melanoma Community Lag-3 data starting to come in and combination of Lag-3+Nivo shows great PFS

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      MelMel
      Participant
      Great news since we have another combo immunotherapy in our arsenal. I think melanoma is like a stroke in a sense since the medical world has a saying,  “Different stroke for different folk” and same is with melanoma. As long as it saves lives and side effects are manageable we are good although this combo has twice the amount of side effects than nivo alone.

      Novel Immunotherapy Boosts Melanoma Outcomes | MedPage Today

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      tim brown
      Participant
      Looks like a valuable tool in the arsenal.

      Questions:

      1. Does this mean that Ipilumimab will take another backward?

      2. Any utility in trying Relatlimab/Ipi as a combo of last resort

      3. The prospects of  a triplet combo?

      4. What’s the likely timeframe for FDA approval?

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        ed williams
        Participant
        Hi Tim, if history is a guide for approvals you usually get big media push before ASCO to get attention from global oncology committee, then FDA does their thing. The first trials back in 2016-17 time frame of Lag-3 + nivo were on patients who had progression on immunotherapy and it showed responses in patients who had Lag-3 expression on staining of tumor. I am not “sure” but I think there might be Lag-3 staining % required from FDA for approval like FDA did for Keytruda (pembro) in lung cancer where they required a certain % of Pd-L1 staining in order to qualify for treatment. Your question about triplets would be interesting but toxicity would be an issue I would think. I think there are a couple more drugs coming like NKTR-214 (pegylated IL-2) and TLR-9 agonists injectables before any triplets would be looked at. Follow the big pharmaceutical news releases is the best way to gage direction of research, where they put the money is where possible new approvals will come from.

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        MelMel
        Participant
        Hi Tim,

        1. Ipi is still number one when it works and has the best sustained response so I do not expect it to take a backward spot. Furthermore, LAG3 appears to work early on in the disease and there are many patients, myself included who became stage IV when first diagnosed. For us who have had the disease for some time, LAG3 may not work as well. Also, there are no sustained response data which is readily available for ipi and nivo.
        2. Trying the Relat/Ipi combo would be too toxic as it stands but perhaps a reduced or a watered down dosage.
        3. As far as the triplet combo, somehow I do not see that one coming about any time soon because it would be like opening a Pandora’s box.
        4. LAG3 was studied and is of particular interest in other solid tumors and with positive results maybe it would be FDA approved sooner. Melanoma patient pool is relatively small and drug companies ideally love when a drug can be utilized for other cancers like breast, lung, colorectal, etc.
        5. The following article maybe of interest: Frontiers | Prognostic Value of Lymphocyte-Activation Gene 3 (LAG3) in Cancer: A Meta-Analysis | Oncology (frontiersin.org)
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      Bubbles
      Participant
      Great work and good summary, Edster!  Here is a post I just completed on anti-LAG-3 (Relatlimab) combined  with Nivolumab (Opdivo) in melanoma.  It contains a link to my first report on anti-LAG-3 from 2014!!!!!! as well as three takes on the current data – to be officially released at ASCO in June – and, for what it’s worth – mine!  HA!

      For those of you who are interested:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2021/05/something-new-in-melanoma-treatment.html

      Thanks for all you do, Edster!  Be well all! – celeste

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      Rosiepup
      Participant
      I’m still looking for the Holy Grail for brain mets and possible leptomenigeal involvement. Could this help do you think? I’m on Temozolomide at the moment and if it’s not working, which I’m not holding out much hope for! I will be getting enco/bini? If they buy me some time, any thoughts re this or any other treatments? Someone told me about proton therapy? And intrathecal? Thanks

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        ed williams
        Participant
        Hi Rosiepup, best advice I could give you is get in touch with MD Anderson and talk with Dr. Isabella Glitza (see following link) and second Dr. that is doing some interesting things is Dr. Michael Davies also at MD Anderson and he is doing some research with something called OXPHOS, see second link and go to 24:30 min mark where he talks about brain research and again at 34:00 min mark he gets into OXPHOS specifically. https://www.onclive.com/view/dr-glitza-oliva-on-intrathecal-intravenous-nivolumab-in-metastatic-melanoma-leptomeningeal    https://www.youtube.com/watch?v=wwup6wOizdo&list=PLOnM_erAQqIBK-ASSZujKruJemGc-FQQR&index=6

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        Rosiepup
        Participant
        Ed thanks so much for that. Spookily I was given Dr Glitza’s name by Dr Tawbi and emailed her yesterday! I’m waiting to hear back from her. The problem is I’m in Scotland and don’t have health insurance. But I would do crowd funding etc if I have to!

        Im just soo worried!🥺 I’ve been fighting this beast for 7 years and I don’t want to give up but it’s not giving up either! Thanks to you and many others here for support and advice 👍💞

        fiona

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      gopher38
      Participant
      This lag-3 sounds very positive.  More arrows in the quiver.  Thanks for sharing.

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