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May 16, 2013 at 6:57 pm #21278TamilsParticipant
I noticed that there are 108 abstracts on nivolumab, but only one on lambrolizumab/MK-3475. I hadn’t realized BMS was so much further along than Merck. Obviously the progression of research on either of these drugs is great news. Since my father is starting the Merck drug in a few weeks, if all goes well, I confess I’m a little disappointed– I wanted to hear more good news about it. Also the preliminary 50% lambrolizumab results now look like 35%. No single person is a statistic, I have to keep reminding myself!
Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1. This study explored the safety and clinical activity of lambrolizumab in patients (pts) with advanced melanoma (MEL). Methods: In this ongoing phase 1b expansion study of MEL pts with or without previous ipilimumab (IPI) treatment, lambrolizumab was administered IV every 2 or 3 weeks until disease progression or unacceptable toxicity. Tumor response was assessed every 12 weeks by independent, central, blinded radiographic review per immune-related response criteria and RECIST 1.1. Results: As of December 1, 2012, 294 pts with MEL were enrolled, including 179 IPI-naive and 115 IPI-pretreated. Pts received lambrolizumab 10 mg/kg (n = 183) or 2 mg/kg (n = 111). Preliminary data from the first 85 consecutive pts dosed before April 25, 2012, who had independent radiologic review available as of December 3, 2012, indicate a confirmed overall response rate per RECIST 1.1 of greater than 35%, pooled across all doses and schedules and including both IPI-naive and IPI-pretreated patients. The median duration of response has not been reached as only 2 pts who had initial response discontinued due to disease progression, but the duration of confirmed responses range from 28+ to 240+ days (up to 8+ months). Among 133 pts who were dosed with lambrolizumab before July 31, 2012, and evaluable for adverse events (AEs) as of September 28, 2012, fatigue (22%), rash (18%), and pruritus (14%) were the most common drug-related AEs (mostly grade 1/2). The incidence of drug-related grade 3/4 AEs was 10% (24% regardless of attribution). Four drug-related cases of pneumonitis were reported, all of grade 1/2. Grade 3/4 drug-related hypothyroidism (n = 1) and hyperthyroidism (n = 1) were noted. Conclusions: Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated MEL pts. These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated MEL. Clinical trial information: NCT01295827.May 17, 2013 at 12:01 pm #60746Catherine PooleKeymaster
Yes the BMS PD1 has been out longer, but the Merck product has moved faster to trials. The final analysis as to which one creates the best response is still unknown. Plus, everyone is different in their response to PD1. So don’t put too much into the press reports and abstracts. Remember that much of this industry driven, not patient driven. But the good news is all of the new therapies coming along because of the industry initiative. It is an exciting time for melanoma and again we will probably be the centerfold of ASCO!May 17, 2013 at 9:17 pm #60747Catherine PooleKeymaster Much influences Wall Street too! http://blogs.marketwatch.com/health-exchange/2013/05/15/bristol-myers-shares-surge-on-anticipated-melanoma-drug-results/May 20, 2013 at 5:05 pm #60748rbruceParticipant DON’t BE DISAPPOINTED! I wouldn’t read anything into the preliminary 50% and current 35% numbers being bantered about. Please note it states “confirmed overall response rate per RECIST 1.1 of greater than 35%, pooled across all doses and schedules and including both IPI-naive and IPI-pretreated patients. ” This is a standard of measurement of RECIST as greater than 35%, not a hard number. This number also includes non-responders. It’s becoming pretty clear that if your tumors do not express the PD ligand, you will not benefit from this particular drug which ups the response rate considerably. Additionally, although I would have given my right arm to get into the BMS trial, the Merck Anti-Pd1 drug seems to be outperforming the BMS drug. Anti-Pd1 drugs, although targeting the same process, work differently by their formulation. My Onc, Dr. Adil Daud at UCSF, said that he is seeing as high as 50- 60% response rate for the Merck trial. I have been on Merck 3475 for over a year now and have gotten better with every scan. My Pet/Ct of scan 2 weeks ago, show that my multiple lung tumors and rib mets no longer light up and my axillary lymph node had an uptake of 1.2, when it was 2.7 12 weeks ago. Anti-Pd1 is one of the greatest advances in Melanoma ever and is now showing similar efficacy in Renal Cell and NSCLC as well. No disappointment PLEASE, the cup is half full!May 20, 2013 at 5:13 pm #60749gostanParticipant That is great news rbruce. Hope it keeps going in that direction.May 21, 2013 at 10:50 am #60750buffcodyParticipant What an amazing time to have acquired this disease. My nephew in 1995 only had interferon. Nothing helped for very long at least. If only he could have had these opportunities. And now his uncle does!! A great blessing and quite humbling.May 22, 2013 at 8:20 pm #60751TamilsParticipant Thanks for the encouraging words, rbruce. I’m so glad to hear you are doing well on MK-3475, and my dad is seeing Dr. Daud too!May 24, 2013 at 4:36 pm #60752JonathanParticipant Just a note on a “competing” anti-PD1 drug, the (now infamous) Cureteck CT-011. Teva paid $$millions for an alliance with Cureteck last year in the hope that their anti-PD1 drug would be effective against melanoma, and a phase I trial was begun with approximately 80 patients enrolled (me included). There was basically no positive response. However, as it was “classified” as an anti-PD-1 molecule and treatment, we are all excluded from participation in any other anti-PD1 trial (Merck, BMS, or other). Nevertheless, the recognition of its failure has led Teva to cut its ties to Cureteck this past January as a result of a review of trial results….the Bloomberg report in January said after a review of clinical and biochemical data, Teva made its decision. Also, the CT-011 “melanoma cancer results may be announced in the three months through June, according to Teva. The partners in CureTech are weighing the implications of Teva’s decision, Clal said in a statement today.” I have not heard any results being announced at ASCO…It would be hopeful for us if Teva or CureTech would abandon the claim that CT-011 is an effective anti-PD1 agent, but I imagine I’m way too optimistic on this one…Are there other ex-CT-011 users out there that would be interested in writing a joint letter to BMS or Merck about this developing situation?
This story does emphasize that there are differences in effectiveness of drugs aimed at the same target molecule, so it will be important to see if BMS’ or Merck’s anti-PD1 turns out to be a better risk.
JonathanMay 27, 2013 at 12:20 am #60753Ferris2001Participant
Jonathan, I would certainly be willing to throw my name on something regarding the Curetech “PD-1” as I would like to have access to the real PD-1 drugs at some point.
Curetech’s anti PD-1 just made me tired…….but that was probably the Benadryl!May 28, 2013 at 12:08 am #60754JonathanParticipant
Ferris, Glad to hear of you, and your interest. In fact, I wrote the Bloomberg author of the article on Teva/CureTech and he’s going to call me tomorrow about our situation. Do you know of others in our situation, and what I’d really like to assert is that no one seems to have had a positive response, but we’re all excluded from participating in the active anti-PD1 trials – a catch-22 situation.
Catherine has suggested I post something on a separate thread so it doesn’t get lost and maybe more CT-011 patients will notice. Feel free to get my email from her in any case.
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