Friday, July 11, 2014

Expanded Access for ipi/Nivo combo and Nivo/Opdivo Licensing Application????

Yesterday was a big day for BMS.  We learned that Opdivo, the anti-PD1 product we know as Nivolumab, was approved in Japan.


BMS opened an expanded access program for the IPI and Nivo combo for Stage IV or unresectable Stage III melanoma patients.  No locations are known as yet...typical for these EAP's.  Mucosal melanoma and melanoma patients with treated brain mets that have been stable via MRI for 2 weeks before start of therapy ARE allowed. (That's a big improvement over the usual 8 week stability requirement!)  However, patients must be ipi and Nivo naive and never have been even in the control arm of a trial with same. (This I find RIDICULOUS!!!)  "Prior systemic therapy is permitted if it was completed at least 4 weeks prior to first dose..."  (Which means that prior treatment with IL2, interferon, BRAFi, etc. ARE allowed, but not required.)  No ocular melanoma.  No autoimmune disease. No patient requiring steroids within 14 days prior to treatment.  No HIV, Hep B, or Hep C.   Scuttlebutt says that because ipi is an approved drug patients will have to provide payment for that, via insurance or some source, but the Nivo will be "free"!  Hmmmm....  Bet that leaves a lot of wiggle room for all sorts of administration fees and hospital charges.  Oh least it will provide more options for many.
Here's the link:  ipi and nivo combo expanded access at

Here's the data from the combo per Weber in his chat with Ribas after the ASCO presentations in June of this year:
"Ipi-Nivo Combo  - ...highlight was...the abstract...presented by update of the concurrent ipi/nivo study in 2013...response rate about 45% in an updated expanded cohort of those with nivo at 1mg/kg and ipi at 3mg/kg...for as long as 96 weeks.  The response rate was in the mid-40% range, but of greater importance, the 2-year survival was in the high-70% important landmark in melanoma. ....must be balanced against a 62% rate of grade 3/4 immune-related adverse events, many of which were easily reversible...only about half required an interruption of treatment...Whenever the rate of side effects at grade 3/4 exceeds the response rate, you have to sit up and take notice.  Nonetheless, a 70% plus survival rate at 2 years is outstanding in melanoma."  
Link to synopsis of the original article from June 2013:  Ipi and nivolumab, better together???


BMS is planning "a third quarter submission of a Biologics Licensing Application for Opdivo (Nivolumab) for previously treated advanced melanoma."  Stipulations seem to include patients with unresectable or metastatic melanoma who have been previously treated with ipi and, if BRAF positive, with a BRAF inhibitor.  Though none of that is absolute at this point.  See article:
BMS submission of Biologics License for Nivo

Sadly, if these are the requirements....they echo my fears from May when BMS first announced their Expanded Access Program for Nivolumab along with those requirements:
EAP for BMS anti-PD1

Big day for BMS.  I hope sites and provision of meds for real patients in need happens soon!  They deserve a big day too!!

ONO4538 ~ MDX1106 ~ BMS936550 ~ Nivolumab ~ Opdivo????  Seriously??   OMG!  867-5309!!!  LOL!  WTF is wrong with you people!?????  

Hang in there, peeps!  It's gonna be a bumpy ride!  -  c

PS   Anybody get my joke???  Hee hee hee!  I crack myself up!!! ;>)
I think there's something wrong with my brain!


  1. great news! do you have the response rate of nivolumab/opdivo per cancer type/stage, age group, gender, etc from earlier ASCO or similar presentations? 40% is still scary!

  2. What was presented at this year's ASCO meeting was just an update on the study that is ongoing from can click on the link in the above post to my June 2013 post "Ipi and Nivolumab, better together??" for the details they put out. The patients were all melanoma patients but it does briefly address prior therapies and responses based on the various doses used. Yes, only in melanoma world is a response rate around 40% and a survival rate of 79% at 2 years, with a median survival of 3-4 years, great news. However, in an interview Weber gave after ASCO this year, he did talk about how impressed he and Sznol had been with the "steep responses" many patients experienced along with an 80% rate for tumor regression. He also noted that BRAF status (whether you were BRAF positive or not) made no difference in response when patients were given this combo, nor did the presence of PDL1 seem to affect the results. One unknown that may change the results of the patients that get this current EAP version of nivo and the fact that they must be ipi and nivo naive. Some of the patients in the study from which this data was gleaned had already had ipi. It seems that more and more experts (see the discussion around LAG3 a few posts back) are of the opinion that once treated with an immune therapy, the response to subsequent immune therapies is not as high. Multiple studies have born that out, sadly. However, if that is so, patients in this EAP cohort could, conceivably, have better responses than this data demonstrates. Hope that helps. Yours, Les

  3. Update on my husbands results from his participation in the Ipi/PD1 clinical trial: started early 11/13 stopped treatment 12/28/13 due to grade 4 A/E's. Still monitored as part of the trial but no further treatment allowed. Results: >80% reduction of softball size tumors in his abdomen -remain stable. Lung mets almost imperceptible. Permanent side effects: insulin dependent diabetes; neuropathy and vitigilo. He's living life with it! Playing softball at the moment with our 21 year old twins (needs a designated runner). May leave the trial soon. Will be interesting to know if he had the combo. Suspect he did. Thanks for posting all the data.

  4. KG: So sorry for such unfortunate side effects and having to stop the treatment. However, that is a wonderful response and I have hope that the stability will be maintained for a long time. I just posted more data about the combo trial that your husband serves as a living example of!!! (With additional data that Rick may be interested in as well.) So glad he is living life LARGE. My best to you both. Ratties are AWESOME!!!