ipi and nivo update

Posted By
7/10/2014 10:14pm
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Replies: 6

I have a few more details about the Expanded Access Protocol for the combination of ipi and nivo.

The study has been approved by the FDA, which means it is posted on clinicaltrials.gov. This starts the process of getting sites open. The company is looking first to sites that have experience with the combination as part of the clinical trial process. It will take at least a month, and more likely six to eight weeks to start putting people on the drug, but everyone is working fast to shorten that time.

The study is open to people with Stage IV or unresectable Stage III melanoma, and it includes mucosal melanoma. It does not include ocular (uveal) melanoma because not enough patients with OM have been treated with the combination to know that it works in that population.

BRAF status doesn't matter, and prior treatment with a BRAF inhibitor is allowed. Prior treatment with ipi is not allowed.

Brain metastases must be stable for two weeks.  This is actually great news, as the previous standard has been eight weeks. 

Because ipi is an approved drug it must be provided as a prescription medicine and covered by insurance or some other program.  Nivo will be provided free as part of the protocol.

So what does this mean? That is not entirely clear. Clinical trial data is based on a small group of patients, fewer than 100.  Toxicities were high, with 2/3 of patients having Grade 3 or 4 toxicities.  Toxicities, or side effects, are rated on a scale of 1 to 5, with 5 being death.  Doctors involved in the study say that many of these higher grade toxicities were due to liver enzymes being out of normal range. The patients felt OK and the liver issues were dealt with fairly easily. 

The results of this small study were very impressive. These patients were all in real trouble. They had experience as many as three prior systemic therapies and were now progressing again. Despite this, the dosage being used in the EAP had one and two year survival rates of 94 and 88 percent, respectively. Those numbers are very high.

Everyone in the field is watching this combination very carefully, with hopes that they strong results will hold up as the number of patients increase and as it is used in patients as their first therapy.






BrianP - (7/10/2014 - 11:13pm)

Thanks for the update Tim.  This is fantastic news!  I will be real interested to see what dosage they end up going with for the EAP.  It seems from the data released at ASCO a concurrent combination of the drugs had the best results.  I hope they can make this happen quick.  From just talking to my clincal trial coordinator in the past I know once they get the green light from BMS it still takes a few months from that point to get the program operational.


JoshF - (7/11/2014 - 12:06am)

Thanks Tim. Very encouraging. Just wondering why they would exclude someone previously treated with ipi, especially if there was some type of response.

So someone who had ipi previously could enter trial of just PD-1?



Let's work for better treatments....for a cure!!!!

RJoeyB - (7/11/2014 - 6:37am)

Also remember that BMS has announced a separate EAP for nivolumab alone for patients who have already tried and failed ipilimumab.  I think it was announced in May and while details on locations have thus far been scarce, we're still in that 6-8 week period where they're still ramping things up, I assume.  Hopefully there will be more details about enrollment opportunities forthcoming very soon.



JoshF - (7/11/2014 - 8:12am)

Thanks Joe...

Let's work for better treatments....for a cure!!!!

Anonymous - (7/13/2014 - 9:36am)

Why not just Nivolumab alone , when the early test results show an equal or better response using Nivolumab as a mono theraphy vrs.a combination of  Ipi and Nivo??

ed williams - (7/13/2014 - 10:20am)

Dear Anonymous, if you take a look at the ASCO 2014 interviews with Dr. Mario Sznol from Yale on youtube it would give you current data on the concurrent study of Nivolumab and Ipilimumab. He reports on the study which includes 53 patients reported at the 2013 ASCO. With overall survival curves of 85% at one year and 79% at two years. Other current info can be found on video " Immumotherapy- The Silver Bullet Against Cancer" sponsored by the Milken Institute on prostrate cancer. Speakers include Pam sharma from MD Anderson,Jedd Wolchok from Memorial Sloan -Kettering, Elliot Sigal MRA, and Charles Drake John Hopkins. Hope this information will be helpfull. Ed