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J. Shahidi



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    MA09 - Immunotherapy Combinations (ID 390)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (ID 4712)

      15:32 - 15:38  |  Author(s): J. Shahidi

      • Abstract
      • Presentation
      • Slides

      Background:
      Trials of anti-EGFR necitumumab and anti-PD1 pembrolizumab demonstrate the anti-tumor activity of each agent in NSCLC.

      Methods:
      Single-arm, multicenter Phase 1b study to investigate effectiveness and safety of necitumumab combined with pembrolizumab in patients with Stage IV NSCLC (NCT02451930). In Part A, escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W. In the absence of dose limiting toxicity, Part B (expansion cohort) was planned with necitumumab 800 mg in 27 squamous and 27 nonsquamous NSCLC patients. Major eligibility criteria included: progression after ≥1 platinum-based chemotherapy, and ECOG PS 0-1. Study objectives were to evaluate tolerability and ORR by RECIST 1.1. PD-L1 status was centrally assessed using PD-L1 IHC 22C3 pharmDx assay (considered negative, weak positive, strong positive if <1%, 1-49%, ≥50% of tumor cells were stained, respectively).

      Results:
      The interim analysis population includes 34 nonsquamous patients (median age 61 years, 68% men, 21% never smokers, PD-L1 status: negative, 50% [17/34]; positive weak/strong, 15% [5/34]/15% [5/34]; unknown 21% [7/34[BJ1] ]). Median follow-up was 6.0 months. Ten patients (29.4%) had PR (confirmed and unconfirmed) (PRs by PD-L1 status: negative, 18% [3/17]; positive weak/strong, 60% [3/5]/40% [2/5]; unknown status, 2 patients). DCR was 67.6%. PFS rate at 6 months was 55.1% (95% CI, 36.2-70.6); median PFS was 6.9 months (95% CI, 2.7-NR). Most common Grade ≥3 AEs were skin rash (9%), hypomagnesemia (9%), VTE (9%) and increased lipase (9%); 1 patient died due to an AE (respiratory tract infection). Five patients (14.7%) discontinued therapy because of an AE. Figure 1



      Conclusion:
      Safety profile corresponds to individual profiles for both drugs, with no additive toxicities. These preliminary data suggest activity of this combination in a pretreated nonsquamous NSCLC population, irrespective of PD-L1 status.

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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
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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): J. Shahidi

      • 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.