Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
OA11.02 RANDOMIZED PHASE 1B/3 STUDY OF ERLOTINIB PLUS
RAMUCIRUMAB IN FIRST-LINE EGFR MUT + STAGE IV NSCLC: PHASE
1B SAFETY RESULTS
Kazuhiko Nakagawa 1 , Luis Paz-Ares 2 , Santiago Ponce 2 , Jesus Corral 3 , Oscar
Vidal 4 , Ernest Nadal 5 , Katsuyuki Kiura 6 , Jingyi Liu 7 , Shuang He 7 , Joseph Treat 7 ,
Rita Dalal 8 , Pablo Lee 9 , Martin Reck 10
1 Kindai University Faculty of Medicine, Osaka-Sayama/Japan, 2 Hospital Doce
de Octubre, Madrid/Spain, 3 Hospital Virgen Del Rocío, Sevilla/Spain, 4 Hospital
Universitario La Fe, Valencia/Spain, 5 Institut Català D’Oncologia, L’Hospitalet,
Barcelona/Spain, 6 Okayama University Hospital, Kitaku, Okayama/Japan, 7 Eli
Lilly and Company, Indianapolis/IN/United States of America, 8 Formerly Eli Lilly
and Company, Bridgewtaer/NJ/United States of America, 9 Eli Lilly and Company,
Bridgewtaer/NJ/United States of America, 10 Lungen Clinic Grosshansdorf,
Airway Research Center North (Arcn), German Center for Lung Research (Dzl),
Grosshansdorf/Germany
Background: Ramucirumab, an antiangiogenic IgG1 VEGFR2-targeted
monoclonal antibody, and erlotinib, an EGFR tyrosine kinase inhibitor, are
both active in advanced NSCLC. This global phase 1b/3 study (NCT02411448)
will assess safety, tolerability and efficacy of the combination of ramucirumab
with erlotinib in previously untreated patients with EGFR mutation-positive
stage IV NSCLC. Here we report phase 1b safety results. Methods: Eligible
patients with ECOG PS 0-1, an activating EGFR mutation, and previously
untreated stage IV NSCLC received ramucirumab 10 mg/kg intravenously
on day 1 of repeating 14-day (± 3 days) cycle and erlotinib 150 mg orally daily.
Treatment continued until disease progression or unacceptable toxicity.
The primary objective of part A was to assess the safety and tolerability, in
terms of dose limiting toxicities (DLT), of adding the recommended dose
of ramucirumab for phase 3 (part B) to standard dose erlotinib. Data were
analyzed separately for Japan (JP) (cohort 1) and US/EU (cohort 2). The DLT
assessment occurred during the first 2 cycles (approximately 28 days).
Results: As of Dec 16th, 2015, 14 patients were treated in the phase 1b part
of this trial and 12 were DLT evaluable (6 JP; 6 US/EU). Overall, 6 grade (Gr) 3
treatment-emergent adverse events (TEAE) were noted, with at least one
TEAE in 5 patients; no serious adverse events or Gr 4-5 TEAEs occurred. In
the JP cohort the median age was 73 (64-79), 57% had ECOG PS 1 and 29%
had a history of smoking. Four patients (57%) experienced a Gr 3 TEAE, of
which one was a DLT (elevation of alanine aminotransferase) while the others
(hypertension [n=2], dermatitis acneiform, and diarrhea) were not DLTs. In
the US/EU cohort the median age was 71 (31-83), 86% had ECOG PS 1, and no
patients had a history of smoking. One patient experienced Gr 3 TEAE of rash;
no DLTs were observed in this cohort. Conclusion: Enrollment on the phase 1b
portion of this trial is complete and the safety results were consistent with
previous combinations of antiangiogenic/erlotinib in this patient population.
No unexpected toxicities were identified. Phase 3 enrollment has been
initiated maintaining the dose of ramucirumab at 10 mg/kg Q2W.
Keywords: Erlotinib, EGFR, VEGF, ramucirumab
OA11: ANGIOGENESIS IN ADVANCED LUNG CANCER
TUESDAY, DECEMBER 6, 2016 - 11:00-12:30
OA11.03 A RANDOMIZED, MULTI-CENTER, DOUBLE-BLIND PHASE
II STUDY OF FRUQUINTINIB IN PATIENTS WITH ADVANCED NON-
SMALL CELL LUNG CANCER
Shun Lu 1 , Jianhua Chang 2 , Xiaoqing Liu 3 , Jianhua Shi 4 , You Lu 5 , Wei Li 6 , Jinji
Yang 7 , Jianying Zhou 8 , Jie Wang 9 , Lei Yang 10 , Zhiwei Chen 11 , Xiangdong Zhou 12 ,
Zhe Liu 13 , Ye Hua 14 , Weiguo Su 14
1 Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong
University, Shanghai/China, 2 Department of Medical Oncology, Fudan University
Shanghai Cancer Center, Shanghai/China, 3 Department of Pulmonary Oncology,
307 Hospital of the Academy of Military Medical Sciences, Cancer Center, Beijing/
China, 4 2Nd Chest Onocology Department, Linyi Tumor Hospital, Linyi/China,
5 Chest Cancer Department of Cancer Center, West China Hospital, Chengdu/China
6 Cancer Center, The First Hospital of Jilin University, Changchun/China, 7 Guangdong
Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of
Medical Sciences, Guangzhou/China, 8 Respiratory Diseases, The First Affiliated
Hospital, College of Medicine, Zhejiang University, Hangzhou/China, 9 Deparmtne
of Thoracic Medical Oncology, Peking University, School of Oncology, Beijing Cancer
Hospital and Institute, Beijing/China, 10 Oncology Department, Nantong Tumor
Hospital, Nangtong/China, 11 Department of Shanghai Lung Cancer Center, Shanghai
Chest Hospital, Shanghai Jiao Tong University, Shanghai/China, 12 Respiratory
Department, Xi Nan Hospital, Third Military Medical University, Chongqing/China,
13 Oncology, Beijing Chest Hospital, Capital Medical University, Beijing/China,
14 Hutchison Medipharma Limited, Shanghai/China
Background: Targeting the tumor microenvironment, such as tumor
angiogenesis, has led to the successful development and approval of a
number of targeted therapies thereby changing the standard of care for
many types of cancer. However, treatment options are limited in third-line
non-small cell lung cancer (NSCLC) patients. Fruquintinib is a potent and
highly selective oral kinase inhibitor targeting vascular endothelial growth
factor receptors and is currently in late stage development for multiple
cancers. This Phase II study was designed to evaluate the efficacy and safety
of fruquintinib in third-line NSCLC patients (NCT02590965). Methods: A
total of 91 patients were randomized to receive best supportive care (BSC)
plus fruquintinib or BSC plus placebo in a 2:1 ratio from 12 Chinese clinical
centers. Fruquintinib initial dose was 5 mg once daily and treatment was
given in every 4-week cycle (3 weeks treatment followed by 1 week off). The
primary objective was to compare progression free survival (PFS) between
the two treatment groups. Secondary efficacy parameters included objective
response rate (ORR), disease control rate (DCR), overall survival (OS). Tumor
response was assessed per RECIST 1.1. Results: As of August 7, 2015, median
PFS was 3.8 months for the fruquintinib group comparing with 1.2 months
for the placebo group (hazard ratio=0.27, p