119P - A phase 2 randomized open-label study of ramucirumab (RAM) plus first-line platinum-based chemotherapy in patients (pts) with recurrent or advanced...

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic Malignancies
Non-Small Cell Lung Cancer
Presenter Sachdev Thomas
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors S. Thomas1, R.C. Doebele2, D. Spigel3, M. Tehfe4, M. Reck5, S. Verma6, A. Zimmermann7, E. Alexandris8, P. Lee8, P. Bonomi9
  • 1University of California San Francisco-Fresno, 94158 - Fresno/US
  • 2University of Colorado Anschutz Medical Campus, Aurora/US
  • 3Sarah Cannon Research Institute, Nashville/US
  • 4Centre Hospitalier de l’université de Montréal, Montreal/CA
  • 5Lung Clinic Grosshansdorf, Dept of Thoracic Oncology, Member of the German Center for Lung Research (DZL), Grosshansdorf/DE
  • 6University of Calgary, Calgary/CA
  • 7Eli Lilly and Company, Indianapolis/US
  • 8Eli Lilly and Company, Bridgewater/US
  • 9Rush University Medical Center, Chicago/US



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.


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/m2 + carboplatin AUC=5/cisplatin 75 mg/m2 (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.


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.


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


Eli Lilly and Company, Indianapolis, IN


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.