The pandemic does not stop the scientific research against cancer promoted by Nibit Foundation, which in the last 12 months, has developed 6 clinical studies, all coordinated by the Immuno-Oncology Center (Cio) of the Sienese University Hospital. The result of this commitment is concretized in particular in three experiments, unique in the world for characteristics and results.
First of all, the Nibit-M2 study shows that 41% of patients with melanoma and brain metastases are alive at 5 years, thanks to the combination of two immunotherapy molecules, nivolumab and ipilimumab. And, in a rare and very difficult to treat cancer like mesothelioma, the study Nibit-Meso-1 demonstrates the value of retreatment with immunotherapy and the possibility of using tumor mutational burden (Tmb) to predict response to this treatment approach. Finally, the Nibit-ML1 study aims to indicate a new way to overcome resistance to immuno-oncology in lung cancer and melanoma. The research is presented today at an online press conference.
“These studies, which lay the foundations for changing daily clinical practice, testify to the dedication of the Nibit Foundation researchers who, even in these difficult months due to Covid-19, have continued to work to make new clinical trials available to cancer patients “he explains Michele Maio, president of the Nibit Foundation, director of the chair of Oncology of the University of Siena and of the IOC of the Aou Senese. “Today in the Siena Center there are about 300 patients, 25% more than in 2019, involved in over 50 active clinical trials. The consequences of the pandemic – he reports – are beginning to be evident in our wards where we observe people with very advanced neoplasms, because they have delayed treatment or ignored suspicious symptoms, avoiding going to hospital. We cannot undermine the efforts made by the cancer community in recent years, scientific research must not stop and the Nibit Foundation is at the forefront ”.
Specifically, the Nibit-M2 study enrolled 80 patients with melanoma and brain metastases. “In 2020, in Italy, 14,900 new cases were estimated and about 50% of patients with melanoma develop brain metastases. For the first time in the world we have broken the dogma that immunotherapy does not work in these cases, “says Dr. Anna Maria Di Giacomo, coordinator of the IOC Phase I and II clinical trials program.” The Phase 3 study Nibit-M2 represents the ideal continuation of the Nibit-M1 study, published in 2013 in ‘Lancet Oncology’. The most important novelty is the evidence that, thanks to the combination of nivolumab and ipilimumab, 41% of treated patients are alive at 5 years compared to 10.9% with fotemustine “.
Another road opened by the Nibit Foundation goes in the direction of identifying with ever greater precision the patients who can respond to immunotherapy, as highlighted by the Nibit-Meso-1 study, which involved 40 patients with mesothelioma. “Our goals are, on the one hand, to provide the best therapy to every person diagnosed with cancer, and on the other hand to make the best use of available resources“, continues Maio.
“To achieve these results – he argues – we need a ‘solid’ biomarker and Tmb, which measures the number of molecular mutations in the tumor, goes precisely in this direction. To assess the mutational load it is necessary to analyze a large amount of genes. The test is performed on tumor tissue, thanks to modern genome analysis techniques that make use of next-generation gene sequencing. And it must be performed at the time of diagnosis: so the clinician has a complete molecular ‘photograph’ for each patient and can identify which they will respond better to immunotherapy “.
The third study is Nibit-ML1, promoted also thanks to the contribution of Bristol Myers Squibb and Astex Pharmaceuticals. “It started in October 2020, during the second wave of the pandemic – says Anna Maria Di Giacomo, principal investigator -. A total of about 20 Italian centers will be involved and 160 patients are expected to be enrolled, 80 with advanced melanoma and 80 with lung cancer, who have not responded to a previous immunotherapy treatment. The aim of the research is to understand the mechanisms of resistance to immuno-oncology in order to overcome them “.
“We know about 50% of patients with melanoma respond to long-term immunotherapy – Maio continues -. In lung cancer the percentage is approximately 35%. To increase these numbers, one of the strategies to be followed is to make cancer cells more ‘visible’ to the immune system, for example by using hypomethylating drugs. We want to analyze the efficacy of the combination of nivolumab and ipilimumab with a hypomethylating molecule in patients who have failed a previous therapy with antibodies directed against PD-1 / PD-L1 already available in daily practice “.
“The scientific basis of this study was developed within the Airc 5Xmille project, which includes 5 important Italian institutions and is coordinated by the Siena Center. And thanks to the commitment of the Sienese university hospital, in May 2020, we also inaugurated the new Phase I Clinical Trials Center, which will make it possible to welcome and follow in an increasingly effective way the cancer patients who belong to it from all over Italy ”, he concludes.