Clinical Trial Results of MM-398 in Pancreatic Cancer

Transcript:Johanna Bendell, MD: Caio alluded to this newly approved agent for the treatment of pancreas cancer, MM-398. George, can you tell us a little bit about, what in the world is this thing, and what's the data that we saw, and where do we go?

George P. Kim, MD: I’ll try. It’s a little confusing, but it’s basically a nanoparticle liposomal irinotecan. So, 80,000 particles of the drug are in these liposomes, and the belief is that there’s longer circulation, more favorable pharmacokinetics, and the drug then lodges into leaky vessels around the tumor, and then accesses the tumor. And that’s how you get more activity. So, that’s the biology behind, Onivyde, is the name of the drug MM-398.

The study that evaluated the drug is the NAPOLI study. It had nothing to do with Italy. It was done over in Taiwan and in the US, but it was a little bit confusing. It started off as a monotherapy Onivyde arm, and then a 5-FU control arm from CONKO-003. So that’s how the study started off. Along the way, they got information back, safety data from a colorectal phase I trial saying that you combine it in a FOLFIRI-type regimen. So, at the end of the day, there were two stepwise comparisons, a monotherapy 5-FU and then the FOLFIRI-type regimen versus the 5-FU.

At the end of the day, the result was that the combination, this new FOLFIRI regimen, was superior to 5-FU. There was a benefit of about two months. So that’s where we are. It was approved in late October of 2015 for second-line therapy for patients that are refractory to gemcitabine. So, that really keeps it wide open. You only have to be treated with gemcitabine. For example, there were some locally advanced earl- stage patients in the trial. If they developed metastatic disease after resection or adjuvant treatment, technically they’re available to get Onivyde in this 5-FU/Onivyde regimen and then 398 regimen.

There were patients also treated with Abraxane in that trial. There were a lot of MPACT Abraxane/gemcitabine patients that went directly into this trial, and so it will be interesting to see what their outcomes are. But I think Dr. Rocha Lima said earlier, we’re starting to have to think about sequencing. This is pancreatic cancer, folks. We didn’t think about that sort of thing for a long time, but now we’ve got to be a little smarter and think about sequencing as we start off. Very interesting drug. It’s great that we have a new treatment in pancreatic cancer and that’s what’s available.

Johanna Bendell, MD: Good problem to have, right?

George P. Kim, MD: Yeah.

Johanna Bendell, MD: Caio, you’ve used MM-398. What’s been your thought? Have you used it? Where do you think it’s going to fall?

Caio Rocha Lima, MD: First of all, nice set up from George. But the NAPOLI trial showed that single agent MM-398 was not superior to 5-FU, leucovorin. So it’s not a single-agent drug for second-line pancreatic cancer. It’s to be combined with 5-FU. The data is telling us that it is still irinotecan, to some extent. You have GI toxicity as the main toxicity. Grade 3 diarrhea was less frequent than what has been reported with the nanoparticle form of irinotecan.

Having said that, grade 1 diarrhea is significant, up to four bowel movements a day. And grade 2 is five, six bowel movements a day. And grade 3 is over six episodes of diarrhea a day. So, even grade 1 and grade 2 can impact one’s quality of life, and the incidence of that is significant, even with the nanoparticle form of irinotecan. Myelosuppression is something to take into account. We’re talking about second-line treatment, but patients may need to receive growth factor support if they suffer from neutropenia. And we have may have some drug delays due to thrombocytopenia as well.

Transcript Edited for Clarity