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A. Zimmermann



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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      119P - A phase 2 randomized open-label study of ramucirumab (RAM) plus first-line platinum-based chemotherapy in patients (pts) with recurrent or advanced non-small cell lung cancer (NSCLC): Final results from squamous pts (ID 174)

      12:30 - 13:00  |  Author(s): A. Zimmermann

      • Abstract

      Background:
      Vascular endothelial growth factor receptors (VEGFR) and their ligands are key regulators of angiogenesis and implicated in pathogenesis of NSCLC. RAM, a human IgG1 monoclonal antibody, specifically binds to VEGFR-2 thereby preventing receptor activation and angiogenesis. In a phase 2 trial (NCT01160744) addition of RAM to platinum-pemetrexed chemotherapy demonstrated clinical activity and acceptable safety in pts with advanced non-squamous NSCLC; here we report data from squamous (SQ) NSCLC pts treated with RAM in combination with first-line gemcitabine plus platinum chemotherapy.

      Methods:
      Eligible pts had Stage IV SQ NSCLC, ECOG PS ≤ 2, and no prior VEGF/VEGFR therapy nor chemotherapy for stage IV disease. Pts were randomized 1:1 into either Arm C: gemcitabine 1000 mg/m[2] + carboplatin AUC=5/cisplatin 75 mg/m[2] (GEM + Cb/Cis) or Arm D: ramucirumab 10 mg/kg + gemcitabine + carboplatin/cisplatin (RAM + GEM + Cb/Cis). Pts received first-line therapy from 4 to 6 cycles (21-day cycle); patients in Arm D, in absence of progressive disease, entered a maintenance phase with RAM alone. Primary objective was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), change in tumor size (CTS), duration of response and safety.

      Results:
      140 pts were randomized (GEM + Cb/Cis: 69; RAM + GEM + Cb/Cis: 71). The median PFS was 5.4 m GEM + Cb/Cis and 5.6 m for RAM + GEM + Cb/Cis; HR 0.88 (90% CI, 0.64, 1.22; p = 0.52). Median OS was 11.3 m for GEM + Cb/Cis and 10.4 m for RAM + GEM + Cb/Cis; HR 0.93 (90% CI, 0.68, 1.27; p = 0.68). ORR was significantly improved in RAM + GEM + Cb/Cis (46.5%) compared to GEM + Cb/Cis (24.6%) (p = 0.007). No statistically significant difference was observed in DCR and CTS between the two arms. Grade ≥ 3 adverse events occurring in > 10% of pts on RAM administered arm were: anemia, neutropenia and thrombocytopenia.

      Conclusions:
      The primary endpoint of PFS was not met. The addition of RAM to GEM + Cb/Cis significantly improved ORR in pts with SQ NSCLC with no new unexpected safety findings.

      Clinical trial identification:
      NCT01160744 JVBL

      Legal entity responsible for the study:
      Eli Lilly and Company, Indianapolis, IN

      Funding:
      Eli Lilly and Company, Indianapolis, IN

      Disclosure:
      R.C. Doebele: Grants from Ignyta, Threshold Pharmaceuticals, Strategia; patent from NTRK1 FISH; royalties paid to Abbott Molecular; Licensing fees for biologic materials Ariad, Loxo, Chugai, Blueprint Medicines; other from Ariad, Trovagene, Guardant Health, AstraZeneca. D. Spigel: Novartis Speakers Bureau (uncompensated). M. Tehfe: Advisory board committee and Honoraria for speaker: Lilly, Celegene, BMS, Merck. M. Reck: Personal fees from Boehringer-Ingelheim, Hoffmann-La Roche, Lilly, MSD, BMS, AstraZeneca, Celgene, Merck, Pfizer, outside the submitted work. A. Zimmermann, E. Alexandris, P. Lee: Employee and stockholder of Eli Lilly and Company. P. Bonomi: Personal fees from Eli Lilly, Roche Genentech, Pfizer, Celgene, Bristol Myers Squibb, Astra Zeneca, Merck, outside the submitted work. All authors have declared no conflicts of interest.