1245P - A phase 2 randomized open-label study of ramucirumab (IMC 1121B; RAM) in combination with platinum-based chemotherapy in patients (pts) with recurre...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Robert Doebele
Authors R. Doebele1, D.R. Spigel2, M. Tehfe3, S. Thomas4, M. Reck5, S. Verma6, S. Yurasov7, R. Camidge8, P. Bonomi9
  • 1Medical Oncology, University of Colorado, 80045 - Aurora/US
  • 2Sarah Cannon Research Institute, Nashville/US
  • 3Hematology-oncology, Centre Hospitalier de l’université de Montréal, H2L4M1 - Montreal/CA
  • 4Oncology, Oncology Hematology Associates of Central Illinois, 61615 - Peoria/US
  • 5Thoracic Oncology, Hospital Grosshansdorf, 22927 - Grosshansdorf/DE
  • 6Medical Oncology, Sunnybrook Odette Cancer Center, M4N 3M5 - Toronto/CA
  • 7ImClone Systems, 08807 - Bridgewater/US
  • 8University of Colorado, 80045 - Aurora/US
  • 9Hematology And Oncology, Rush University Medical Center, 60614 - Chicago/US

Abstract

Background

Vascular endothelial growth factor (VEGF)-mediated angiogenesis plays an important role in NSCLC pathogenesis. RAM is a fully human IgG1 monoclonal antibody that inhibits VEGF receptor-2 (VEGFR-2) binding and signaling. This study investigates RAM in combination with first-line platinum-based chemotherapy in advanced NSCLC.

Methods

NSQ pts with Stage IV NSCLC, ECOG PS ≤ 2, adequate hematologic, hepatic and renal function were randomized to either Arm A: pemetrexed + carboplatin/cisplatin or Arm B: RAM + pemetrexed + carboplatin/cisplatin, once every 3 weeks. The primary analysis will be when 103 progression-free survival (PFS) events are observed in NSQ pts. This pre-planned interim analysis was performed when 61 NSQ PFS events were observed. Other interim endpoints: objective response rate, disease control rate (DCR), and safety.

Results

Arm A (n = 71) median (medn) age 64, 63% male (M), 37% female (F), ECOG PS 0-1 / 2 (91.6% / 5.6%). Arm B (n = 69) medn age 64, 52% M, 48% F, ECOG PS 0-1 / 2 (89.9% / 7.2%).

Interim efficacy analyses Arm A (N = 71) n (%) Arm B (N = 69) n (%)
PFS Events Censored Median (months) 90% CI 37 (52) 34 (48) 4.3 (3.8, 5.7) 24 (35) 45 (65) 6.3 (5.7, -)
Best Response PR SD DCR (SD + PR) 26 (37) 25 (35) 51 (72) 30 (44) 30 (44) 60 (88)

Nonhematologic adverse events (AEs) were fatigue (61%; 17% Grade[G]3), nausea (55%; 7% G3), vomiting (36%; 4% G3), constipation (30%; 1% G3), hypertension (HTN) (6%; 1% G3), proteinuria (4%; 0 G3), on Arm A; fatigue (63%; 12% G3), nausea (51%; 10% G3), vomiting (33%; 8% G3), constipation (27%; 0 G3), HTN (19%; 10% G3), proteinuria (5%; 0 G3) on Arm B. Hematologic AEs were anemia (A) (55%; 16% G3), neutropenia (N) (23%; 16% G3), thrombocytopenia (T) (23%; 12% G3) on Arm A; A (39%; 8% G3), N (33%; 13% G3), T (31%; 15% G3) on Arm B.

Conclusions

Based on interim analyses of PFS and acceptable tolerability and safety, RAM may provide clinical benefit in combination with first-line platinum-based chemotherapy in NSQ NSCLC. Enrollment of pts in squamous Arms C and D is ongoing.

Disclosure

R. Doebele: Research funding: ImClone Systems, Eli Lilly & Co., Pfizer Inc. Honoraria: Boehringer Ingelheim, Abbott Laboratories, Pfizer Inc. Stock: Ariad (< $10,000).

M. Reck: Honoraria for Lectures: Lilly, Hoffmann-La Roche, AstraZeneca, Daiichi-Sankyo Advisory Board (compensated): Lilly, Hoffmann-La Roche, AstraZeneca, Daiichi-Sankyo, Pfizer, Merck, BMS.

S. Verma: Advisory Board and honoraria from Eli Lilly.

S. Yurasov: I am employed by Eli Lilly and own Lilly stock.

D.R. Camidge: Advisory role and honoraria: ImClone Reserach Funding: Eli Lilly.

All other authors have declared no conflicts of interest.