Paolo Ascierto Transcript - Pegs Summit Europe 2016

Immune Checkpoint in Melanoma

Christina Lingham:	Hi, everyone. I'm Christina Lingham from the PEGS Europe Summit. I'm delighted to have the opportunity to speak with Paolo Ascierto to talk with us about immune checkpoint in melanoma. He will be giving a talk at the Novel Therapies for Cancer Track on November 3rd and 4th in Lisbon. Paolo, thank you for joining us. Could you summarize the highlights of your research?
Paolo Ascierto:	Yes, of course. First of all, at the moment, I'm a medical oncologist. At the moment, I'm the Director of the Melanoma Cancer Immunotherapy and Innovative Therapies Unit at the National Cancer Institute in Naples, Italy. Anyway, because to have this position, I work for several years. More than 50 years as Vice Director of the Clinical Immunology Department. During my work in my life in this institution, I worked on clinical immunology. I treated a lot patients, mainly melanoma patients with a vaccine. Vaccine like peptide, vaccine like anti-idiotypic vaccine, and also we sell basic vaccine. We've participated in important clinical trial with cancer that [inaudible 01:18] melanoma. We enrolled more than 160 patients. We collected a lot of experience. Unfortunately, the majority of cases in this case was not a factor, because the recent vaccination, but we collected a lot of experience not only with the vaccine but also with [inaudible 01:40]. Subsequently, my experience was about immunotherapy treatment in patients. Of course, during the years, we worked also to some by markers and also immunological features of recent kinds of cancers. Consider that one of my first work when we treated patients with anti-idiotypic vaccine and we monitored these patients with some analysis like the evolution of the subset [ol-y-site 02:16] it was 1994/1995 and we observed the patients who did not respond had an increase of the CP25 expressed on the [imp-o-site 02:31] [inaudible 02:32] blot. This was so strange because the CP25 is the receptor of areas too and this is related with an activation and at the time we did not understand why the site of these high activation patients to rest and had no benefit. After several years and in 2002 it was discovered that [tee-reg-ulat-or 02:56] cell and these are the cell with highest expression of CP25, and we observed that the increase of the [tree-rotr 03:05] cells was one of the mechanisms for some immune therapy. Just to say that in the past year we worked a lot and today we know more and some of the things that we observed in [inaudible 03:20] in those families of the [in-fac-sis 03:23] for clinical trial are now well known and it is probably is the [fac-sis 03:30] of immune therapy.
Christina Lingham:	All right, let's get started. Your talk at the Digital PCR Symposium is about early response monitoring with circulating tumor DNA in lung cancer. How has Digital PCR changed your research in oncology?
Paolo Ascierto:	Digital PCR has really kind of revolutionized our ability in oncology to applied precision medicine to cancer patients. In lung cancer we now know that greater than about 60% of the main type of lung cancer has a known driver oncogene. Through genomic approaches identifying the genes that cause cancer has had predicted benefits to many patients here at UCSD and at our cancer center and across the country at many cancer centers. There's been large programs and initiatives built about how to use precision medicine and targeted therapy for patients in whom have main oncogene drivers. Digital PCR has really allowed and facilitated the ability to look for small genomic equivalents of DNA in samples such as tissue, blood, urine, other body fluids. In doing so has allowed the possibility to detect cancer, survey cancer over time. Qualitatively and quantitatively analyze how the cancer's changing on top of different therapies and through time. We have used this to build novel tools, to look at treatment response. Digital PCR has increased sensitivity compared to traditional PCR; lower costs. It's permitted a larger understanding of variations within samples because we now understand that tumors are heterogeneous, with a lot of complexity with regard to different clonal as well as subclonal populations that make the cells within a cancer very diverse. Through technology such as Digital PCR, we now have the microscope to evaluate this disease.
Christina Lingham:	Have you gained insight from your research that in turn has enhanced your current efforts with immune checkpoint therapies?
Paolo Ascierto:	The importance of transformational research it's important we should have samples from our patients biopsy and liquid biopsy because these [can-al-pass 03:52] better understanding who are the patients who can reach long-term survival and better understanding who are the patients who don't respond to immune therapy and the possible mechanisms of resistance and how we can overcome these. I think that the possibility to do [con-fir-ma-a-reas-arch 04:16] and the possibility to have samples from our patients it's one of the most important things that we should do. Also practice this can help both the [inaudible 04:33] we'll start very soon a clinical trial but the sequence in melanoma the sequence with target cell terribly similar. When we collect biopsy and those blood samples for this patient with [inaudible 04:46] some important points in the sequence in order to better understand what I just discussed.
Christina Lingham:	Can you outline what you consider to be some of the greatest obstacles in Immunotherapy and checkpoint inhibition?
Paolo Ascierto:	The most important obstacle is the cost because these are high cost treatments the benefit is not for all the patients. This is the most important obstacle. I think that we've been [tor-stant 05:12] of course the market, we've been [tor-stant 05:13] to predict who are the patients who can have long-term benefit. I think that the [ped-al-one 05:20] is not the right [bio-market 05:22] at the moment because this is positive people want respond better and we have the highest respond patients but patients with [ped-I-al-one 05:32] negative can still respond so we can not forget about these patients because also these patients can be treated. We need other kind of [bio-market 05:41] for instance something like [mar-co-stab-elli 05:47] was found very interesting in patients with colon cancer and who were treated with immunotherapy therapy. Not in general would I think that would be real important [inaudible 05:59] would be the immunoprofiling then this a large [con-fec-t 06:03] so this means patients with a particular [in-fe-pla-te 06:06] in the tumor [micro-varia 06:09] might have the presence of a specific gene signatures. I already described about the [car-co-go-ma 06:14] signatures in patients we was treating melanoma [in-bel-is-ma 06:18]. This experience could easily bring [bor-sta-nt 06:24] findings that can help us in deciding the better treatment for the better patients and of course do the important for selected patients in order to optimize the cost. Another obstacle is of course resistance because immunotherapy work in very good manner of course not in all the patients and next challenge will be how to make cancer who not respond to immunotherapy in cancer that may respond and respond well to immunotherapy.
Christina Lingham:	What are some of the most exciting recent discoveries in immunotherapy? And how has your work changed as a result?
Paolo Ascierto:	I think that at least in the field of melanoma because we have a lot of datas today the possibility to cure patients, we know from the [pre-lim-a 07:22] history that [inaudible 07:23] we can cure 2 patients out of 10 because important meta-analysis which considered patients treated with [inaudible 07:35] in clinical trial [inaudible 07:37] program the 20% of these patients is still alive at 10 years. We can affirm that the 20% of patient are cured. This is amazing, today, when we treat patients and we can communicate that you can reach a long-term survival of 10 years. It's amazing. Of course it's just for the 20% of patients, but if you consider that only a few years ago before 2011 a [me-ll-I-on 08:08] survival for our melanoma patients was between 6 and 9 [ans 08:12] and only the 25.5% were alive at 20 years. Very few patients reached 2 years. Now we have 20% still alive at 10 years. This is amazing. [we-do-ped-one 08:24] today probably we can reach more. So the [per-ec-tion 08:29] is of about 40% [inaudible 08:33]. And with a combination because this is another exciting record discovery immune therapy the possibility to combine two different checkpoint inhibitors probably we can reach more. In terms of long-term survival. OF course, we can combine immune therapy with only other 2 that we are available though so we can sequence these. Today we can consider immunotherapy as the fourth pillar in the treatment against cancers.
Christina Lingham:	How do you see the future progress of immunotherapy and which approaches should be given higher consideration?
Paolo Ascierto:	I have no doubts is combination. Combination means not only to combine immunotherapy with immunotherapy. I just discussed the possibility to combine for instance [kel-imo 09:21] with [ev-ol-o-ma 09:21] but combination means to combine immunotherapy with all the other tools that we are available against cancer. This means with chemotherapy, it means [rad-I-ther-apy 09:31] it means also with [cali-ther-apy 09:33]. Consider that in melanoma the combination immunotherapy immunotherapy seems work very well, but probably this is not for the other disease. In melanoma chemotherapy is not so active but is active in [for-is-inal 09:46] cancer, breast cancer, [ovar-an 09:48] cancer we can combine checkpoint inhibitor with chemotherapy. Do you just in order to give you hear about this possible combination. Or radio-therapy we know that radio-therapy may [syn-er-gize 10:00] with checkpoint inhibitor can make the figures of these a little bit higher and also with target therapy. We can also sequence in immunotherapy targeted. Combination approach of course in sequencing, because sometimes sequencing is also good and a good approach. In the future, and of course we will have different approach for the different kind of cancers because each cancer has a specific characteristic and on the base of this characteristic we should find the best combination approach that we can.
Christina Lingham:	Paolo, thank you for your time and insights today. That was Paolo Ascierto of the Institute Au Nationale Tumare Napole he'll be speaking at the novel therapies for cancer track this November 3rd and 4th in Lisbon. If you'd like to hear him in person, go to pegsummiteurope.com for registration information and enter the key code podcast. I'm Christina Lingham, thank you for listening.