Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
POSTER SESSION 2 – P2.06: SCIENTIFIC CO-OPERATION/RESEARCH GROUPS
PHASE II + NK –
TUESDAY, DECEMBER 6, 2016
P2.06-016 PHASE 2 STUDY OF RAMUCIRUMAB PLUS WEEKLY
DOCETAXEL IN STAGE IV NSCLC FOLLOWING PROGRESSION AFTER
PLATINUM-BASED CHEMOTHERAPY
Martin Sebastian 1 , Santiago Ponce 2 , Petros Nikolinakos 3 , Rocio Varea 4 , Bo
Chao 5 , Annamaria Zimmermann 6 , Ekaterine Alexandris 5 , Pablo Lee 5 , Frederico
Cappuzzo 7
1 University Hospital Frankfurt, Goethe University, Frankfurt/Germany, 2 Hospital
Doce de Octubre, Madrid/Spain, 3 University Cancer and Blood Center, Athens/
GA/United States of America, 4 Eli Lilly and Company, Madrid/Spain, 5 Eli Lilly
and Company, Bridgewater/NJ/United States of America, 6 Eli Lilly and Company,
Indianapolis/IN/United States of America, 7 Department of Oncology-Hematology,
Ausl Romagna, Ravenna/Italy
Background: Ramucirumab, a human IgG1 monoclonal antibody, binds
to vascular endothelial growth factor (VEGF) receptor 2, competing
with VEGF-A, -C and –D and thereby preventing receptor activation and
angiogenesis. The phase 3 REVEL trial demonstrated the addition of
ramucirumab to docetaxel improved survival in patients with stage IV NSCLC
following progression after platinum-based chemotherapy, independent
of histology. The approved dose of docetaxel in NSCLC patients after
progression on prior platinum-based chemotherapy is 75 mg/m2 every 3
weeks. The most common toxicity associated with this dosing regimen is
myelosuppression, specifically neutropenia. In order to reduce the incidence
of myelosuppression, various weekly docetaxel dosing regimens have been
evaluated. These studies have suggested that weekly docetaxel can provide
better tolerability with at least similar efficacy. This phase 2, single arm,
open-label study (JVDN; NCT02831491) is designed to assess a potential
reduction in the rate of grade ≥3 neutropenia and febrile neutropenia with
weekly docetaxel in combination with ramucirumab, as compared to historical
safety data from the REVEL trial. This study will also assess safety and
efficacy of ramucirumab with weekly docetaxel in patients who received prior
immunotherapy for NSCLC.
Methods: Study JVDN includes patients (n=50) with stage IV NSCLC, with
measurable disease and ECOG performance status 0-1 who have experienced
disease progression from one prior platinum-based therapy which may have
included bevacizumab. Prior immunotherapy for NSCLC is permitted. Patients
will receive the approved ramucirumab dose regimen for NSCLC (10mg/kg IV)
on day 1 every 3 weeks, followed by weekly docetaxel (35 mg/m2 IV) on days 1,
8 and 15 every 4 weeks. Treatment may continue until disease progression or a
criterion for discontinuation is met. The primary endpoint is to assess safety,
as measured by the rate of grade ≥3 neutropenia (CTCAE v4.0). Secondary
endpoints for all patients include the rate of treatment-emergent febrile
neutropenia, overall safety, pharmacokinetics (ramucirumab), and efficacy.
Additional secondary endpoints of safety and efficacy will be assessed in
patients who did or did not receive prior immunotherapy. An exploratory
endpoint is to assess the association between biomarkers with safety and
clinical outcomes. The primary and final analyses will occur after 31 and 50
patients, respectively, have completed ≥12 weeks of treatment to determine
if grade ≥3 neutropenia and febrile neutropenia are reduced with the
investigational weekly docetaxel treatment as compared to historical safety
data from REVEL. Results: Not applicable Conclusion: Not applicable
Keywords: angiogenesis, VEGF, ramucirumab, docetaxel
POSTER SESSION 2 – P2.06: SCIENTIFIC CO-OPERATION/RESEARCH GROUPS
PHASE II + NK –
TUESDAY, DECEMBER 6, 2016
P2.06-017 AMETHYST NSCLC TRIAL: PHASE 2 STUDY OF MGCD265
IN PATIENTS WITH ADVANCED OR METASTATIC NSCLC WITH
ACTIVATING GENETIC ALTERATIONS IN MET
Lyudmila Bazhenova 1 , Dong-Wan Kim 2 , Luigi Cavanna 3 , Ji-Youn Han 4 , Jong
Seok Lee 5 , Hoon-Kyo Kim 6 , Byoung Chul Cho 7 , Marshall Schreeder 8 , Ashiq
Masood 9 , Igor Rybkin 10 , Melissa Johnson 11 , Britt Boleman 12 , Marta Batus 13 ,
Estelamari Rodriguez 14 , David Hong 15 , Pasi Jänne 16 , Raul Mena 17 , Frederico
Cappuzzo 18 , Ivor Percent 19 , Vanessa Tassell 20 , James Christensen 20 , Demiana
Faltaos 20 , Richard Chao 20 , Hirak Der-Torossian 20 , Diane Potvin 20 , Ranee
Mehra 21
1 Internal Medicine, Division of Hematology-Oncology, University of California
San Diego, La Jolla/United States of America, 2 Seoul National University Hospital,
Seoul/Korea, Republic of, 3 Azienda Unità Sanitaria Locale Di Piacenza-Ospedale
Guglielmo Da Saliceto, Piacenza/Italy, 4 Center for Lung Cancer, National Cancer
Center, Goyang/Korea, Republic of, 5 Seoul National University Bundang Hospital,
Seongnam/Korea, Republic of, 6 College of Medicine, St. Vincent’S Hospital, the
Catholic University of Korea, Suwon-Si/Korea, Republic of, 7 Division of Medical
Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/
Korea, Republic of, 8 Clearview Cancer Institute, Huntsville/AL/United States of
America, 9 Washington University School of Medicine Siteman Cancer Center, St.
Louis/MO/United States of America, 10 Henry Ford Health System, Detroit/MI/
United States of America, 11 Medical Oncology, Sarah Cannon Research Institute,
Nashville/TN/United States of America, 12 Greenville Health System, Greenville/
AL/United States of America, 13 Hematology, Oncology and Cell Therapy, Rush
University Medical Center, Chicago/IL/United States of America, 14 Mount Sinai
Medical Center, Miami/FL/United States of America, 15 The University of Texas MD
Anderson Cancer Center, Houston/TX/United States of America, 16 Dana-Farber
Cancer Institute, Boston/MA/United States of America, 17 Providence Saint Joseph
Medical Center, Burbank/AL/United States of America, 18 Oncology, Istituto Toscano
Tumori, Livorno/Italy, 19 Florida Cancer Specialists, Fort Myers/AL/United States of
America, 20 Mirati Therapeutics, San Diego/CA/United States of America, 21 Medical
Oncology, Fox Chase Cancer Center, Philadelphia/United States of America
Background: MGCD265 is a potent, orally available, small molecule RTK
inhibitor of MET and Axl, both of which mediate signals for cell growth,
survival, and migration. The Amethyst NSCLC trial is designed to evaluate the
activity of MGCD265 in patients with NSCLC exhibiting genetic alterations
involving MET. Alterations in MET, including gene amplification and/or
genetic mutations, occur in approximately 7% of NSCLC cases converting
MET to an oncogene capable of driving cancer development and progression.
Amplification of MET has been associated with a poor prognosis in NSCLC.
In addition, various genetic mutations result in the deletion of exon 14 in
MET mRNA (METex14del) and the subsequent loss of the Y1003 regulatory
binding site for CBL ubiquitin ligase, required for MET degradation and
signal attenuation. Loss of the Y1003 binding site of MET results in sustained
MET signaling, which has been implicated as an oncogenic driver in a
subset of NSCLC. The importance of MET as a driver is demonstrated in
xenograft models of NSCLC with METex14del and MET amplification, and
where MGCD265 induces tumor regression. Additionally, confirmed partial
responses have been observed in pts with NSCLC characterized by METex14del
who were treated with MGCD265 in the Phase 1 setting. Methods: Pts
with platinum pre-treated NSCLC characterized by activating genetic MET
alterations identified in tumor tissue or circulating tumor DNA (ctDNA) are
eligible for this multi-center, global, Phase 2 trial. Pts are assigned to one of
four cohorts based on the type of MET dysregulation and detection method:
1) mutations in tissue, 2) amplification in tissue, 3) mutations in ctDNA,
and 4) amplification in ctDNA. The primary endpoint is Objective Response
Rate (ORR) in accordance with RECIST 1.1; a Bayesian Predictive Probability
Design is applied independently to each cohort. Secondary objectives include
safety, tolerability, response duration, survival, correlation between tissue
and ctDNA testing, and PK/PD. This study is currently open globally, and
recruitment is ongoing. Results: Section not applicable. Conclusion: Section
not applicable.
Keywords: MET, NSCLC, ctDNA, EXON 14 DELETION
POSTER SESSION 2 – P2.06: SCIENTIFIC CO-OPERATION/RESEARCH GROUPS
PHASE II + NK –
TUESDAY, DECEMBER 6, 2016
P2.06-018 MULTICENTER, SINGLE-ARM PHASE II STUDY OF NAB-
PACLITAXEL/CARBOPLATIN IN UNTREATED PS2 PATIENTS WITH
ADVANCED NSCLC: TORG1426
Yasuko Ichikawa 1 , Nobuhiko Seki 1 , Shinobu Hosokawa 2 , Akihiro Bessho 2 ,
Tsuneo Shimokawa 3 , Hiroaki Okamoto 3 , Sakiko Otani 4 , Yoshiro Nakahara 4 ,
Makiko Yomota 5 , Yukio Hosomi 5 , Kyoko Murase 6 , Kazuma Kishi 6 , Shunichiro
Iwasawa 7 , Takashi Nishimura 8 , Takashi Kasai 9 , Yoichi Nakamura 9 , Koshiro
Watanabe 10
1 Medical Oncology, Internal Medicine, Teikyo University School of Medicine,
Itabashi,tokyo/Japan, 2 Department of Respiratory Medicine, Japanese Red
Cross Okayama Hospital, Okayama/Japan, 3 Department of Respiratory Medicine
and Medical Oncology, Yokohama Municipal Citizen’S Hospital, Yokohama,
Kanagawa/Japan, 4 Department of Respiratory Medicine, Kitasato University
Hospital, Sagamihara,kanagawa/Japan, 5 Thoracic Oncology and Respiratory
Medicine, Tokyo Metropolitian Cancer and Infectious Diseases Center Komagome
Hospital, Bunkyo,tokyo/Japan, 6 Department of Respiratory Medicine, Respiratory
Center, Toranomon Hospital, Minato,tokyo/Japan, 7 Department of Medical
Oncology, Graduate School of Medicine, Chiba University, Chiba,chiba/Japan,
8 Department of Respiratory Medicine, Kyoto Katsura Hospital, Nishikyo,kyoto/
Japan, 9 Division of Thoracic Oncology, Department of Medical Oncology, Tochigi
Cancer Center, Utsunomiya,tochigi/Japan, 10 Thoracic Oncology Research Group,
Yokohama,kanagawa/Japan
Background: No standard of care exists for ECOG Performance Status (PS)
2 patients with advanced non-small cell lung cancer (NSCLC) and therefore
clinical practice ranges from supportive care to combination chemotherapy.
It was first reported that the combination therapy with carboplatin (CBDCA)/
pemetrexed significantly improved survival for PS2 patients with advanced
non-squamous NSCLC (J Clin Oncol 31:2849-2853.2013). However, due to the
limited utilities of this regimen, establishment of other combination therapy
is warranted in PS2 patients with especially squamous NSCLC or unfavorable
renal function. On the other hand, in CA031 trial, CBDCA/nab-paclitaxel
(PTX) demonstrated a significantly higher response rate (RR) compared with
S566 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017