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August 3, 2013 at 11:38 pm #60655jamesaParticipant
I am thrilled that this drug appears to be working for you. You deserve a break because of Curetech’s PD1 drug disqualifying from other PD1 trials. It is just not fair to you that you cannot get into another PD1 trial. I just get angry with the clinical trial process and Pharma compassionate use rules & regulations.
It makes me wonder how dealing with cancer and qualifying for clinical trials is all a crap shoot. I am still sadden the Pati lost her fight. After Pati had realized that Merck PD1 was not working for her, she petitioned for the Mek drug and was denied! If Pati had been granted under compassionate use the MEK drug combo with Braf then maybe should would not have gotten involved with the TIL process, etc. and things would have turned out differently for Pati. My heart breaks for Pati’s husband & 2 boys. Here is a link with Pati’s husband’s post
I know this is speculation on my part, but I guess after reading Pati’s blog that her husband recently describes Pati’s last days, I am still angry that Pati had to die because of random circumstances
Jonathan, my buddy, I admire your positive attitude and wish the very best outcome for you on this new drug. I wish you and Francoise a long life together.August 4, 2013 at 2:46 pm #60656
Thanks for your heartfelt good wishes – much appreciated. Celeste had just also alerted me to Pati’s husband sorrowful post – very powerful and sad. She was so compassionate and smart, a real fighter and alive human being.
This fight to find good treatments for advanced melanoma is extremely frustrating, often unfair, filled with blind alleys, and at the same time more hopeful than it’s ever been. We can be driven into making choices we never thought we’d consider out of a lack of reasonable alternatives. It feels terrible to have one’s oncologist say “I’m sorry but I have nothing more to offer you.” And we can wish for pharmas, the FDA, etc to make decisions on promising drug development more rapidly (and compassionately), but in many cases that’s simply not how things work – often very depressing.
We have a lot of fallen warriors, a lot of wonderful and very real souls who have not made it, but there are increasing numbers who are, for whatever reasons, coping and making this more of a chronic disease state. So in spite of it all, there really is hope now.
Take good care, and make your days special,
JonathanAugust 4, 2013 at 3:30 pm #60657
Very well put, Jonathan. Pati would be proud. You are awesome! A tremendous inspiration to many! Love, cAugust 4, 2013 at 5:19 pm #60658 Pati was my sister in body and soul, and we became sister organizations. I will not let her work die with her. Bettina and I started right away to get this year’s MICAB meeting back on track. Pati and I met three years ago at the first MICAB meeting. We had a glorious time before the meeting, as she showed me Brussels and I met her family for dinner one night. Her boys were precious and loved my farm animal pictures. She was brilliant at the meeting. We next met in Zurich and she talked of dying and leaving her organization to MIF. I refused to listen.. she wasn’t going to die. And then we went for the PD1 in LA. I flew out to be with her for the treatment. Another wonderful close time together. Sadly she didn’t respond to PD1. I will never forget our last long hug. Then the long TIL journey where our communication was sparse.
We will have a grant program in Pati’s memory starting soon, going to patients only..it is the best way I know to honor her.August 4, 2013 at 6:49 pm #60659
Most fitting, Catherine. I know you must miss Pati very much. The two of you have accomplished a great deal for all of us. It is appreciated. I hope you know. CAugust 6, 2013 at 5:23 pm #60660 This week’s report on this trial continues the good news. I’m now about to get only my third infusion (at week 6 or 7 , depending how you count – start of 3rd cycle). The scans show either continued decreases in half on the big ones, and still considerable on the small ones, with some resolving – my new favorite word). My anemia seems to be over – hemoglobin is up to 12 with the help of an iron shot, and probably no more intestinal bleeding, is the guess.
What I learned about the drug today after talking with Dr. Infante:
1. The muscle pain/knee instability I’ve started feeling has been seen in other ADC patients at the highest dosages (and I’m at their highest, 2.8 vs 2.4 mg/kg for most which he suspects will be the settled dosage). So if it continues or gets worse, he may lower my dosage, since he wants me exercising again. They’ve learned a lot about dosage and side-effects from prior ADC trials, like the successful breast cancer one, so they’ve got a better handle on the right dosage and expected side effects, since the chemo involved is the same, or essentially so.
2. The response I’m getting is among the very best they’ve seen with this drug, after only 2 infusions, so they’re hoping it will continue (so am I) . In responders, they very commonly see an early reduction of some percentage, and then decreasing rates of shrinkage in tumor burden, and/or the achievement of stability, which in most cases is still a very satisfactory situation if the starting symptoms are tolerable.
3. BAD NEWS. The company is delaying start-ups (at least involving Yale) for a while, perhaps a year. So those of you who are interested, certainly keep tuned, but don’t think it’s going to be widely available in 3 months. For me and those already on it here and LA, they’re at least considering an early amendment that would reduce the visits to Nashville after a few months to only 1 every 3 weeks.
Bottom line – this is a great drug for me, and I can’t help thinking that it’s going to be effective for a very large proportion of advanced melanoma patients in a few years (what – 5? 20?).
Best to everyone,
JonathanAugust 7, 2013 at 11:32 pm #60661AnonymousGuest
Great news Jonathan!
You know, I can’t help but imagine how well this and IPI might work together. They are two very different approaches that would seem, to me anyway, very complimentary and not antagonistic.
I wonder what Dr. Infante would think about such a combo.
JeffAugust 8, 2013 at 1:26 am #60662
I was thinking the same thing on the way home. I’m sure we’re not alone, but obviously the first thing is to see how effective this drug is alone and what the profile is over a few years of treatment (because I asked, and Infante said the intention is to keep responders on the drug indefinitely – don’t want to drop the ball). And they’ve got to do survivorship curves and all that. However, at that point, you’d think a combo with an immunological drug like Ipi or anti-PD1 might provide a double-whammy, or some advantage. Simply in terms of percentage responders, if this drug really has about a 50% response rate, and anti-PD1 is in the mid-30s, a patient should have a chance of responding to one or the other of something in the 75-80% rate, if given in sequence (say anti-PD1 first, then if there’s no response, or after progression, give them this DEDN drug). If you gave both simultaneously, this drug works considerably faster, so you’d know at 6 weeks if it was kicking in, while the others start apparent responses weeks later, so you could see that effect, plus any possible positive interaction. Who knows? They don’t expect total NED achievement with this drug, but with anti-PD1 and Ipi, you’ve got most responders subsequently progressing again sometime in the future, so maybe there might be great advantage in getting both. I bet this won’t be investigated for years, however.September 5, 2013 at 8:21 am #60663MarianAParticipant
Hi Jonathan. Catherine advised me to follow your posts re ADC. I know nothing of this but yesterday we learned that our son, after initially responding to the TIL treatment he had in Manchester, England, seems to be no longer responding. His tumours have remained the same and a tumour has regrown in the site of one of the tumours harvested for T cell extraction prior to treatment. I cannot find any mention of PD1 trials/treatment in the UK. Do you know whether my son would be able to join an ADC trial in the US? My son is a soldier and most likely contracted melanoma during his tours in Iraq and Afghanistan. He has done so much for us, I would go to the end of the earth for him. Any help or advice would be much appreciated. Thank youSeptember 5, 2013 at 5:48 pm #60664 PD1 trials are available in the UK. I have a list of some to open soon and others that are accruing the patient needs to be IPI (yervoy) naïve. Has he had Yervoy? That is also approved in the UK. I have a couple of doctors I can recommend, but not sure how far it would be for you. James Larkin at the Royal Marsden, and Mark Middleton at Oxford would know about PD1 coming to their institutions. The trial Jonathan in on last time I checked was only in the states and Australia. I will check again and post back here.September 5, 2013 at 8:44 pm #60665 Dear MarianA,
I’m sorry about your son’s situation, and I know how you must feel. I will answer you rather quickly and then go on to describe my current situation in more detail.
First off, the ADC trial I’m on is very encouraging, but still in its infancy – stage 1 (safety, trying to establish the maximum tolerable dosage), and very limited numbers of patients slowly enrolled (thusfar, primarily Nashville, Los Angeles, a site in Australia, and now coming on, 2 more, one in Detroit and a second in Australia – you can look up more details, I believe on clinicaltrials.gov). The total number of patients thusfar is around 50, perhaps a few more. You can also search google for the drug name, DEDN6526A (Roche/Genentech). They also are now planning to expand the phase I trial to other sites, but I don’t yet know where or when – probably in 2 or 3 months. I have absolutely no idea if it’s going to be expanded to sites in the UK or Europe. I would guess the UK will lag somewhat. This would be your major drawback, since, after the first month in residency, he would be required, under current protocol, to make weekly visits to the site for simple monitoring and once every 3 week infusions (taking about 2 hours total). They may also be amending this protocol to a more flexible schedule, but thus far, that’s it – very crazy, I know. The trial currently runs for a year, but the current intention is for patients to continue to get infusions once every 3 weeks for as long as the patient is progression free. As I’ve written earlier in this thread, I have the definite sense that the drug has great potential and may have a response rate somewhere around 50%, give or take. NED status is not what they generally hope to achieve, but rather some clear response and then continuing stability with no new metastases.
Now I will go on with some more detail on my own circumstance at week 10 on this trial, particularly as it relates to side-effects. This ADC type drug is best described as a “targeted chemotherapy”, meaning it delivers very small doses of a particularly toxic chemotherapy (called Auristatin that cannot be used by itself because of its toxicity) targeting melanoma tumor cells, and thereby avoiding the collateral damage that ordinary chemotherapy causes to normal cells. The estimate is that well over 90% of the drug is taken up by melanoma cells, which is quite incredible, but there still is some “leakage” of the potent chemo to other cells. Hence there are some side effects, rather akin to normal chemotherapy, but the effectiveness of this drug is much greater on melanoma than standard chemotherapy (generally of minimal effectiveness). In my case, my many tumors (small intestines, bowel, lungs, nodes in armpits, etc) began to shrink dramatically in size and activity (measured by PET and CT scans) or disappear by week 6 or even before – what they call a “complete partial response” very early on – very positive. My earlier anemia (caused by tumor bleeding in my intestines) has disappeared, as have other symptoms, so I would be very happy to achieve stability at this point. My next scans will be in a month.
With regard to side effects, the picture is not as rosy as I initially thought, or understood – I thought I was told they would be minimal. I and one other patient at Nashville were given the highest dosage given to anyone (2.8 mg/kg I believe). The other patient “ran into trouble” after 2 infusions, but I showed no side effects until after the 3rd, apparently to their surprise. My side effects are primarily tiredness/fatigue and peripheral neuropathy which has developed in the last 2-3 weeks. This is typical of chemotherapy generally, apparently, and since they’ve now given me a 2 week “holiday” from any treatment and will clearly lower my dosage considerably when it resumes next week, we’re hoping the symptoms will get better, but it’s not a quick or guaranteed process at my age (73). The peripheral neuropathy in particular is one side effect that they worry about as potentially cumulative over time, so getting it under control is a major concern. My leg muscles are currently weak and I walk in a somewhat unsteady manner.
So overall, this is very promising, and I don’t think anyone henceforth will be getting such a high dosage as me, so that the side-effects should be more tolerable (they do think the effects are dosage related). However, given its early stage of development and general lack of availability globally, if I were you, I’d be searching first and foremost for anti-PD1 trial sites. I doubt your son’s TIL experience has disqualified him from anti-PD1 – and certainly it wouldn’t for this sort of ADC chemo trial, either.
JonathanSeptember 6, 2013 at 4:29 pm #60666
Your son would need to enroll in the refractory Pd1 trials because he has had two prior therapies (although not IPI?) There are European sites but none in England right now. If you email me privately, I will give you some sites to check out in Europe:
Thanks again Jonathan for posting your progress and hope your side effects subside soon! Thanks for being a reporter from the trial as you mention the dosage will probably change but phase I is supposed to figure that out so you and others may first suffer the consequences. We’re all thinking of you hoping for the best possible outcome.October 1, 2013 at 6:08 pm #60667
Hi, here’s an update on my experience on this very promising trial and a little more information from Dr. Infante on the prospects.
First, the general prospects for a long-term response. He says the best early indicator for this is the continuing response of breast cancer patients on the ADC/Herceptin drug that was approved by the FDA this spring,, and that he has been involved with for 3+years. He has a patient who has continued to be on this drug with very good response for over 3 years, so that’s very encouraging for all ADC drugs (the one aimed at melanoma, that I’m on, only has been recruiting for a year and a half, so not such a long track record). The issue is to find the lowest effective dosage that will then give the least side effects (most usually peripheral neuropathy).
Second, my “report card” at 3 months, the first major benchmark. He gave me an A- on the scan reports. Largest tumors continue to shrink, although at a lower rate. The largest are now 50% or less of their initial dimensions, there are no new tumors anywhere, and the small ones (scattered mostly in my lungs) are either not growing or disappearing. There are some questions about thickening in intestines that may be very old pre-melanoma things, so I think it’s really a great report
Recommended dosage and a holiday. Because of the good report, he’s going to continue me on the lowest dosage level (1.8 mg/kg) and also I’m going to get another “holiday” from the treatment (meaning I don’t have to get an infusion for a month).
Side effects…My anemia has come back, for no clear reason, so he’s giving me another round of iron injections. Those worked wonderfully well before, so I assume they’ll do the same this time. The peripheral neuropathy (numb finger tips and now toes, plus weakness in my thighs) continues to be a worry, but is most likely because of the lasting effects of the heavy-duty dose of drug I got the first 3 rounds (2.8 mg/kg – established the maximum tolerable dose at 2.2).
So thats it!October 1, 2013 at 10:58 pm #60668tbeauParticipant
Thank you for the update Jonathan. Enjoy your “holiday.” Your posts are very promising and hopeful and I always look forward to reading them!October 2, 2013 at 12:37 am #60669 Go Johnnie, GO! You are awesome and it seems that your ADC is living up to the status of its recipient!! That is all really great news! I give you an A+! However, sorry about the neuropathies! Hope they will diminish with your break and decreased dose. Love you! C
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