Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
stages (Simon 2-stage design). If more than 7 of the first 26 have PFS >6 months,
we will continue to a total of 55 patients. Observing a total of 50 progression
events will provide 90% power to identify a 6 month PFS of >45%. Correlative
biomarkers including immunological biomarkers from blood and pleural fluid
will also be collected. These will be correlated with disease activity, effects
of study drug and clinical outcomes to detect any biomarkers and potential
predictive biomarkers. Results: As of 1 st July 2016, 7 patients have been enrolled
and recruitment is ongoing. There have been no grade 3 or 4 toxicities and no
cardiac or ophthalmological toxicities. Main toxicities are grade 1 mucositis
and dry mouth. 1 patient had hyperphosphatemia which resolved with dietary
modification. Conclusion: AZD4547 is well tolerated with no grade 3 or 4
toxicities shown at this stage in a small number of patients. Recruitment
commenced in April 2016 and stage 1 is projected to be completed by April 2017.
Keywords: Mesothelioma, fibroblast growth factor, clinical trial, second line
treatment
POSTER SESSION 2 – P2.06: SCIENTIFIC CO-OPERATION/RESEARCH GROUPS
MESOTHELIOMA AND SCLC –
TUESDAY, DECEMBER 6, 2016
P2.06-027 RANDOMIZED PHASE II STUDY OF ANETUMAB
RAVTANSINE OR VINORELBINE IN PATIENTS WITH METASTATIC
PLEURAL MESOTHELIOMA
Raffit Hassan 1 , Ross Jennens 2 , Jan Van Meerbeeck 3 , John Nemunaitis 4 ,
George Blumenschein 5 , Dean Fennell 6 , Hedy Kindler 7 , Silvia Novello 8 , Annette
Walter 9 , Danila Serpico 10 , Jonathan Siegel 11 , Ariadna Holynskyj 11 , Barrett
Childs 11 , Cem Elbi 11
1 Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute,
Bethesda/MD/United States of America, 2 Epworth Richmond Hospital, Richmond/
ACT/Australia, 3 University Hospital Antwerp, Edegem/Belgium, 4 Mary Crowley
Cancer Research Centers, Dallas/TX/United States of America, 5 University of
Texas MD Anderson Cancer Center, Houston/TX/United States of America, 6 Cancer
Research Uk Centre, University of Leicester & Leicester University Hospitals,
Leicester/United Kingdom, 7 Section of Hematology/Oncology, University of
Chicago, Chicago/IL/United States of America, 8 Department of Oncology -
University of Turin, Thoracic Oncology Unit, Orbassano/Italy, 9 Bayer Ag, Berlin/
Germany, 10 Bayer S.P.A., Milan/Italy, 11 Bayer Healthcare Pharmaceuticals Inc,
Whippany/NJ/United States of America
Background: Mesothelioma is a rare but aggressive cancer with a poor
prognosis. Mesothelin is a cell surface protein that is highly expressed in
mesothelioma and other epithelial cancers. Anetumab ravtansine (BAY
94-9343), a novel fully human anti-mesothelin IgG1 antibody conjugated
to the maytansinoid tubulin inhibitor DM4, has shown encouraging
efficacy in mesothelioma patients in a phase I study. To further explore the
possible benefit of antibody-drug conjugate therapy for mesothelioma,
we initiated a randomized, open-label, active-controlled, phase II trial to
evaluate the efficacy and safety of anetumab ravtansine in patients with
metastatic pleural mesothelioma (MPM) overexpressing mesothelin and
who have previously progressed on platinum/pemetrexed-based firstline
chemotherapy (NCT02610140). Methods: Patients (≥18 years) with
unresectable locally advanced or metastatic MPM are eligible. Patients
should have recurrent or relapsing disease after having previously receiving
first-line treatment with pemetrexed-based chemotherapy, with or
without bevacizumab. Obligatory biomarker sampling will be performed
on all patients at pre-screening and mesothelin-positivity as determined
by Ventana MSLN (SP74) companion diagnostic assay as a requirement for
entry. The primary objective is to test the superiority of anetumab ravtansine
monotherapy over vinorelbine in progression-free survival (PFS) per modified
RECIST criteria for MPM per central review. The secondary objectives of this
study include overall survival, patient-reported outcomes (PRO), tumor
response, and safety. Exploratory objectives include immunogenicity of
anetumab ravtansine, pharmacokinetics, and biomarkers of response.
Approximately 210 patients will be randomized in a 2:1 ratio to receive
anetumab ravtansine 6.5 mg/kg Q3W or vinorelbine 30 mg/m 2 QW. Novel
study methods include a grading system for AEs of special interest and the
PRO instruments. Results: This trial is open and currently accruing patients
globally. Conclusion: Section not applicable.
Keywords: antibody-drug conjugagte, Mesothelioma, mesothelin
POSTER SESSION 2 – P2.06: SCIENTIFIC CO-OPERATION/RESEARCH GROUPS
MESOTHELIOMA AND SCLC –
TUESDAY, DECEMBER 6, 2016
P2.06-028 A PHASE 2 STUDY OF PREXASERTIB IN PATIENTS WITH
EXTENSIVE STAGE SMALL CELL LUNG CANCER
Lauren Averett Byers 1 , Lisa Golden 2 , Wei Zhang 2 , Aimee Bence Lin 2 , Martin
Forster 3
1 Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson
Cancer Center, Houston, Hx/AL/United States of America, 2 Oncology, Eli Lilly and
Company, Indianapolis/IN/United States of America, 3 Oncology, University College
London Cancer Institute, London/United Kingdom
Background: Checkpoint kinase 1 (CHK1), plays a role in cell cycle regulation
and DNA damage repair. Prexasertib monomesylate monohydrate
(prexasertib, or LY2606368) inhibits CHK1 and induces replication
catastrophe. As monotherapy, it demonstrated an acceptable safety profile
and preliminary evidence of efficacy in Phase 1. Replication stress, together
with defects in cell cycle checkpoints and/or DNA damage repair pathways
may sensitize tumors to CHK1 inhibitors. Small cell lung cancer (SCLC)
tumors have high levels of replication stress through mechanisms such as
MYC amplification and high rates of TP53 mutations, RB1 loss, and genomic
rearrangements. Preclinical models of SCLC demonstrate sensitivity to
prexasertib monotherapy. As a result, prexasertib is an attractive agent to
evaluate in patients with SCLC. Methods: This is a parallel cohort, nonrandomized,
open-label, multicenter Phase 2 study (NCT02735980) in
patients with extensive disease (ED)-SCLC. Cohort 1 includes patients with
platinum-sensitive disease (objective response to prior platinum-based
therapy with subsequent progression ≥90 days after last platinum dose).
Cohort 2 includes patients with platinumresistant/refractory disease
(patients who either did not have an objective response to prior platinumbased
therapy or had progression 60 sites). An interim futility analysis will be conducted in each
cohort after 29 patients have completed cycle 3 and, if required, the response
is confirmed. Enrollment began in May 2016. Results: Section not applicable.
Conclusion: Section not applicable.
Keywords: extensive stage small cell lung cancer, checkpoint kinase 1,
replication stress
POSTER SESSION 2 – P2.06: SCIENTIFIC CO-OPERATION/RESEARCH GROUPS
MESOTHELIOMA AND SCLC –
TUESDAY, DECEMBER 6, 2016
P2.06-029 PILOT WINDOW-OF-OPPORTUNITY STUDY OF
PEMBROLIZUMAB IN PATIENTS WITH RESECTABLE MALIGNANT
PLEURAL MESOTHELIOMA (MPM)
Hedy Kindler 1 , Mark Ferguson 2 , Yi-Huang Tan 1 , Buerkley Rose 1 , Mehwish
Ahmad 1 , Samuel Armato 3 , Christopher Straus 3 , Theodore Karrison 4 , Tanguy
Seiwert 1
1 Section of Hematology/Oncology, University of Chicago, Chicago/IL/United States
of America, 2 Department of Surgery, University of Chicago, Chicago/IL/United
States of America, 3 Department of Radiology, University of Chicago, Chicago/IL/
United States of America, 4 Department of Public Health Sciences, University of
Chicago, Chicago/IL/United States of America
Background: Although PD-1 inhibitors have demonstrated significant
activity in MPM (Alley, WCLC 2015; Kindler, WCLC 2016), not all patients
benefit. About 1/3 of MPM have high PD-L1 expression and a CD8+ infiltrative
pattern with a gamma-interferon gene expression profile; this phenotype
has been employed in tumors such as melanoma to predict for benefit from
immune checkpoint blockade (Ribas, ASCO 2015; Seiwert, ASCO 2015). The
mechanisms of anti-tumor response in a disease with a low mutational burden
and a distinct macrophage-dominant immune microenvironment remain
poorly understood. Due to the anatomy of MPM, access to tumor tissue
for correlative studies can be problematic without surgery. We therefore
initiated a window-of-opportunity study of pembrolizumab in patients
with resectable MPM (NCT02707666) to better understand the dynamic
changes occurring with PD-1 checkpoint blockade. Methods: Eligible patients
have previously untreated, histologically confirmed, epithelial or biphasic
MPM amenable to maximal surgical debulking via extended pleurectomy/
decortication. Measurable or evaluable disease, PS 0-1, no extra-thoracic
disease, adequate pulmonary and cardiac function, and a free pleural space
S570 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017