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R.R. Hozak
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-035 - EGFR FISH as Potential Predictor of Necitumumab Benefit with Chemotherapy in Squamous NSCLC: Subgroup Analyses from SQUIRE (ID 5708)
14:30 - 14:30 | Author(s): R.R. Hozak
- Abstract
Background:
Necitumumab (Neci) is a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR). In the SQUIRE trial (NCT00981058), the addition of Neci to gemcitabine plus cisplatin (Gem-Cis) in squamous cell lung cancer resulted in a significant advantage in terms of overall survival (OS), but the expression of EGFR assessed by immunohistochemistry was not able to robustly predict the benefit from Neci. In a post-hoc analysis of SQUIRE, EGFR gene copy number gain determined by fluorescence in situ hybridization (FISH) showed a trend towards improved OS (HR=0.70) and progression-free survival (PFS) (HR=0.71) with the addition of Neci. We present the analysis of granular EGFR-FISH data from SQUIRE to examine the potential predictive role of high polysomy (HP) vs gene amplification (GA) as both were included in the “FISH-positive” category.
Methods:
Suitable specimens from SQUIRE patients underwent FISH analysis. Probe hybridization was performed in a central laboratory and each sample was analyzed using the Colorado EGFR scoring criteria. FISH was considered positive in cases of HP (≥40% cells with ≥4 EGFR copies) or GA (EGFR/CEP7 ≥2 or ≥10% cells with ≥15 EGFR copies). The correlation of granular FISH parameters with clinical outcomes was assessed.
Results:
FISH analysis was available for 557 patients (out of 1093); 208 patients (37.3%) were FISH+, including 167 (30.0%) with HP and 41 (7.4%) with GA. The outcome data for HP and GA are reported below:HIGH POLYSOMY GENE AMPLIFICATION Neci+Gem-Cis (N=89) Gem-Cis (N=78) Neci+Gem-Cis (N=22) Gem-Cis (N=19) Median OS in months (95% CI) 12.58 (11.04-16.00) 9.53 (7.16-12.48) 14.78 (10.02-31.51) 7.62 (4.99-16.10) Hazard ratio within subgroup (interaction model) 0.77 (0.55-1.08) p = 0.133 0.45 (0.21-0.93) p = 0.033 Interaction p value 0.189 Median PFS in months(95% CI) 6.08 (5.59-7.59) 5.13 (4.24-5.72) 7.36 (4.27-11.40) 5.55 (2.79-8.34) Hazard ratio within subgroup (interaction model) 0.70 (0.50-0.99) p = 0.044 0.69 (0.33-1.45) p = 0.334 Interaction p value 0.980
Conclusion:
The OS benefit from the addition of Neci to Gem-Cis appeared to be more pronounced in the small subset of patients with GA when compared to HP, but the same trend was not observed for PFS. The potential predictive value of different EGFR FISH parameters should be evaluated in future studies.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-005 - Phase 1 Study of Ramucirumab or Necitumumab in Combination with Osimertinib (AZD9291) in Advanced T790M-Positive EGFR-Mutant NSCLC (ID 4278)
14:30 - 14:30 | Author(s): R.R. Hozak
- Abstract
Background:
Despite the likelihood of an initial response to 1st or 2nd generation EGFR-TKI, EGFR mutant patients develop disease progression. The most frequent mechanism of acquired resistance is the EGFR T790M gatekeeper mutation. Novel treatment options are needed in this treatment resistant patient population. Osimertinib, a third-generation EGFR TKI targeting mutant EGFR including T790M, is an oral, irreversible, selective inhibitor. Ramucirumab and necitumumab are human IgG1 monoclonal antibodies to VEGFR-2 and EGFR, respectively. This phase 1, open-label, multicenter study with expansion cohorts (JVDL; NCT02789345) is designed to evaluate the safety and preliminary efficacy of ramucirumab or necitumumab in combination with osimertinib in patients with advanced EGFR T790M-positive NSCLC who have progressed after EGFR TKI therapy.
Methods:
This study includes patients with advanced or metastatic EGFR T790M-positive EGFR activating mutant (exon 19 deletions or L858R) NSCLC, with measurable disease and ECOG performance status 0-1 who have experienced disease progression on one prior EGFR TKI regardless of prior chemotherapy. Patients previously treated with an EGFR antibody or 3rd generation EGFR TKI for NSCLC are not eligible. In the phase 1a dose de-escalation portion (3+3 design), all patients (n=6 to 24) will be administered daily oral osimertinib (80 mg) with either an initial dose of 10 mg/kg IV ramucirumab on day 1 of every 2-week cycle or 800 mg IV necitumumab on days 1 and 8 of every 3-week cycle. One level of dose de-escalation is planned for each arm. A dose reduction (level -1) to 8 mg/kg IV ramucirumab or 600 mg IV necitumumab is planned if 2 or more patients have DLTs in either arm. After the DLT evaluation, the study will open a dose-expansion portion (phase 1b) and 25 patients in each Arm will receive study treatment until disease progression or a criterion for discontinuation is met. The primary objective is to assess safety and tolerability of ramucirumab or necitumumab in combination with osimertinib. Secondary endpoints include preliminary efficacy and pharmacokinetics. An exploratory biomarker objective includes the assessment of correlations between EGFR-mutations in tissue and serial blood samples with clinical outcomes. Primary analyses will be conducted approximately 6 months after the last patient receives initial dose.
Results:
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Conclusion:
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