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Vincenzo Minotti
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-65 - Immune Gene Expression, Bayesian Network and Genetic Mutation Analysis in Advanced NSCLC Patients Treated with Immunotherapy (Now Available) (ID 1361)
09:45 - 18:00 | Presenting Author(s): Vincenzo Minotti
- Abstract
Background
Immune checkpoint inhibitors (ICIs) have dramatically revoluzionized the therapeutic paradigm for NSCLC, but only a small subset of patients achieves durable benefit. The only adopted predictive biomarker, PD-L1 IHC testing, suffers from some limitations. A better understanding of biomarkers associated with response to ICIs is needed. Here, we studied immune gene-expression and genetic mutation profiles and association with clinical response to immunotherapy in advanced NSCLC patients treated with ICI.
Method
A total of 37 Formalin-fixed, paraffin-embedded (FFPE) samples from advanced NSCLCs were analyzed by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) (ThermoFisher Scientific) on Ion Torrent PGM and Transcriptome Analysis Console (TAC) 4.0 Software. This panel measures the expression level of 395 genes associated with 36 functional groups including checkpoint pathways, lymphocyte regulation and cytokine interactions. Gene network analysis based on Bayesian algorithm was performed by GeneMANIA database querying with the genes selected through mRNA expression analysis. Cancer somatic mutation analysis were performed using Ion NGS Panel on PGM Instrument.
Result
Among 37 FFPE samples only 18 showed more than 300 OIRRA detectable target genes. In this subgroup, gene expression analysis revealed 7 genes (CCR2, CRTAM, FASLG, SELL, TIGIT, TNFRSF4, and TP63) up-regulated and one gene (CXCL8) down-regulated (p-value < 0.05) in ICI-responders compare to ICI-no responders. Bayesian enrichment computational analysis of eight gene expression signature showed a more complex network which involves other 10 genes (SIRPG, GZMK, XCL2, CD8A, CD2, IFNG, SIT1, TAGAP, PTPRC and GZMH), correlated with different functional groups. Three main immune-pathways were identified (p < 0.01) (T cell activation, leucocyte activation and migration) involving TIGIT, TNFRSF4, CCR2 and CXCL8 genes among the gene expression signature identified. Gene mutational analysis was feasible for 28 samples. KRAS mutation was detected in 41% of ICI-responders respect to 12.5% of ICI-no responders. Conversely, no STK11 mutation was found in ICI-responders, consistent with previous reports.
Conclusion
Our results revealed an immune response gene expression signature of 8 genes differentially expressed between ICI and ICI-no responders. Cancer systems biology analysis approach strengthen our findings identifying an immune molecular network and confirm the correlation of the gene expression signature with relevant immune regulatory functions. If validated, our results may have an important role for the development of a robust test to select patients properly and predict immune response to enable precision immunotherapy. Furthermore, TMB assessment in such subset of patients is under investigation and more data will be available for the meeting.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-49 - Nivolumab Plus Ipilimumab (NI) Versus Chemotherapy Plus Nivolumab (CN) in Squamous Cell Lung Cancer (SqCLC): The SQUINT Trial (ID 1557)
10:15 - 18:15 | Author(s): Vincenzo Minotti
- Abstract
Background
Treatment landscape for patients with advanced NSCLC is rapidly evolving, with recent randomized phase III trials demonstrating superiority of chemo-immuno combinations versus chemotherapy alone. Role of chemo-free combinations, including NI, is under investigation with limited available data. Aim of the present trial is to investigate outcome of SqCLC patients when treated with NI or CN.
Method
SQUINT (NCT03823625) is an open-label, randomized, parallel, non-comparative phase II study designed to assess the efficacy of NI (Arm A) or CN (Arm B) in patients with advanced, metastatic SqCLC. Eligibility requires age ≥ 18 years, histologically confirmed stage IV or recurrent stage IIIB SqCLC, p63+/p40+ and TTF- tumour tissue, availability of PD-L1 status, no prior systemic therapy, ECOG performance status 0-1, adequate organ functions. Key exclusion criteria include concomitant radiotherapy or chemotherapy, prior treatment with immune checkpoint inhibitors, untreated brain metastases, other serious illness or medical condition potentially interfering with the study or with NI administration. Patients are randomly assigned 1:1 to receive N 360 mg Q3W plus I 1 mg/kg Q6W (Arm A) or plus platinum-based chemotherapy up to 6 cycles plus nivolumab 360 mg Q3W (Arm B), and stratified by PD-L1 expression (<1% versus ≥1%), presence of bone metastases (yes/no) and liver metastases (yes/no). In both arms, immunotherapy is given until disease progression, unacceptable toxicity, patient refusal and in any case for up to 24 months. Primary endpoint is 1-year overall survival (OS) rate in Arm A and B. Secondary endpoints include: response rate (RR), duration of response (DoR), median progression free survival (PFS) and median OS in Arm A and B, and according to predefined stratification factors. Sample size has been calculated assuming for each arm a minimum acceptable 1-year OS rate of 40% and an auspicated 1-year OS rate of 60%, a power of 90% and a one side significant level of 0.05. Based on such premises, the total number of patients required for the study is 112.
Result
At the time of this analysis a total of 11 Italian Centers are recruiting and 25 subjects have been enrolled.
Conclusion
We expect to conclude enrolment by January 2020.
