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Federica D'Incà
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-03 - Molecular Determinants for Lorlatinib Activity in ROS1 Positive NSCLC: Results of the Prospective PFROST Trial (ID 1566)
09:45 - 18:00 | Author(s): Federica D'Incà
- Abstract
Background
Lorlatinib, an ALK/ROS1 inhibitor, demonstrated activity in ROS1+ NSCLC pretreated with crizotinib. However, molecular events predictive for tumor response during lorlatinib treatment are largely unknown.
Method
PFROST was a prospective phase II trial designed to include ROS1+ NSCLC refractory to crizotinib. Eligible patients were treated with lorlatinib at the daily dose of 100 mg until disease progression. Primary end point was response rate (RR). For all included patients pre-lorlatinib tumor tissue or blood sample collection was mandatory. At the time of lorlatinib failure liquid biopsy was recommended. The samples were then run with the NEOliquid assay, specifically designed for liquid biopsies, or NEOselect, a panel optimized for formalin-fixed paraffin-embedded (FFPE) tumor tissue, covering 39 cancer related genes.
Result
From June 2017 to April 2019, 22 ROS1+ crizotinib refractory lung adenocarcinoma patients were included in 10 Institutions. Median age was 56 years (range 39-82); male/female: 8/14; ECOG PS 0 (N=8; 36.4%), PS1 (N=14; 63,6%); The majority had brain metastases at baseline (N=15; 68.1%), were never smokers (N=13; 59.1%) and received lorlatinib as third line therapy (N=16; 72.7%). In all cases crizotinib was the last therapy line before lorlatinib. At the time of the present analysis, trial completed its accrual and 13 patients are still receiving therapy. A total of 18 patients were evaluable for response and 7 had confirmed complete (N=1) or partial (N=6) responses for an overall RR of 38.8%. In 4 patients, response to therapy was not yet evaluated. A total of 10 tissue biopsies and 20 blood samples obtained after crizotinib and before lorlatinib therapy were collected. For 7 samples analyses are ongoing. Among responders, no patient harbored a secondary ROS1 mutation. Conversely, no response was observed among patients with secondary ROS1 mutations (N= 1 ROS1S1861I, N=1 ROS1 V2054A, N=3 ROS1G2032R). All patients harboring the ROS1G2032R mutation rapidly progressed and maintained this aberration in liquid biopsy at the time of radiological evidence of lorlatinib failure.
Conclusion
In our study lorlatinib confirmed its efficacy in crizotinib resistant ROS1+ NSCLC. Molecular profile of refractory patients suggests reduced efficacy in individuals developing secondary ROS1 mutations after crizotinib failure.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-15 - Phase II Single Arm Study of CABozantinib in Non-Small Cell Lung Cancer Patients with MET Deregulation (CABinMET) (ID 2637)
10:15 - 18:15 | Author(s): Federica D'Incà
- Abstract
Background
Mesenchymal-Epithelial Transition gene (MET) amplification and exon 14 skipping mutations are established oncogenic drivers in non-small cell lung cancer (NSCLC), both occurring in about 4% of cases. In patients with MET amplified or mutated lung cancer, oral MET tyrosine kinase inhibitors (TKI) showed promising activity. The American Food and Drug Administration has recently granted crizotinib a breakthrough therapy designation for MET exon 14 mutation positive NSCLC. Cabozantinib is a novel oral inhibitor of MET and other receptor tyrosine kinases that has shown preliminary activity in MET deregulated NSCLC patients pretreated with crizotinib, although definitive data on its therapeutic role are still missing.
Method
CABinMET (NCT03911193) is a phase II, single arm, multicenter study assessing the efficacy of cabozantinib in subject with MET amplification or MET exon 14 skipping mutation pretreated or not with MET inhibitors. The primary endpoint of the trial is overall response rate. Secondary efficacy endpoints are progression free survival, overall survival and disease control rate. Main inclusion criteria include histologically/cytologically confirmed diagnosis of advanced stage NSCLC, presence of MET exon 14 skipping mutation or MET amplification (MET/CEP7 ratio ≥2.2 on FISH analysis) on archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or circulating tumor DNA, measurable disease, ECOG PS 0-1, at least 1 prior line of standard therapy, adequate organ function. Patients with co-existent driver events or with symptomatic brain metastases are excluded from the trial. Cabozantinib is administered orally at 60 mg once daily until disease progression, patient refusal or unacceptable toxicity. Disease is assessed every 8 weeks. Exploratory biomarker analyses are conducted on archival FFPE tumor tissue and on blood samples collected at baseline, at the time of the first disease assessment and at progression.
Result
The study is currently running in 9 Italian centers. Recruitment started in September 2018 and 6 of the planned 25 patients have been enrolled.
Conclusion
Enrollment will be completed in 24 months.
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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): Federica D'Incà
- 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.
