Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Conversely, the other 49 patients mostly died due to systemic cancer spread,
but all 49 cases had no pain associated with airway symptoms. Therefore,
suffocation death appears to have been avoided in those 49 (85.9%) patients
(Non-suffocation death group). In a univariate analysis, “Stent migration”,
“Tracheal stenosis”, and “Thyroid cancer” were potentially significant factors
regarding suffocation death. In a multivariate analysis, “Stenosis at mid
trachea” was found to be an independent predictive factor for suffocation
death (p = 0.02). Conclusion: Suffocation death can be effectively prevented
by the use of airway stenting treatment. “Stenosis at mid trachea” is the most
problematic factor when attempting to obtain some benefit from stenting
and this may be due to the difficulty of achieving accurate stent (mainly
straight silicon stent) fixation in such lesions.
Keywords: suffocation, airway stent
Conclusion: Steady-state PK was comparable in advanced ALK+ NSCLC
patients taking ceritinib 450 mg with a low-fat meal versus 750 mg fasted.
This study continues to enroll treatment-naïve patients into Part 2 to assess
efficacy across the three treatment arms and assess longer safety follow-up.
Keywords: Ceritinib, ALK, NSCLC
POSTER SESSION 3 – P3.02b: ADVANCED NSCLC & CHEMO-
THERAPY/TARGETED THERAPY/IMMUNOTHERAPY
EGFR –
WEDNESDAY, DECEMBER 7, 2016
POSTER SESSION 3 – P3.02A: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
MISCELLANEOUS –
WEDNESDAY, DECEMBER 7, 2016
P3.02A-036 PHASE 1 STUDY OF CERITINIB 450 MG OR 600 MG
TAKEN WITH A LOW-FAT MEAL VERSUS 750 MG IN FASTED STATE IN
ALK+ METASTATIC NSCLC
Rafal Dziadziuszko 1 , DONG-WAN KIM 2 , ALESSANDRA BEARZ 3 , SCOTT
LAURIE 4 , MARK MCKEAGE 5 , KEUNCHIL PARK 6 , SANG-WE KIM 7 ,
VANESSA Q. PASSOS 8 , KAREN OSBORNE 9 , YVONNE Y LAU 10 , JESSIE
GU 10 , BYOUNG CHUL CHO 11
1 Oncology and Radiotherapy, Medical University of Gdansk, Gdansk/Poland, 2 Seoul
National University Hospital, Seoul/Korea, Republic of, 3 Centro Di Riferimento
Oncologico-Ircc, Aviano/Italy, 4 Medical Oncology, The Ottawa Hospital Cancer
Centre, University of Ottawa, Ottawa/Canada, 5 University of Auckland, Auckland/
New Zealand, 6 Div of HEM/ONC, Samsung Med Ctr, Sungkyunkwan Univ School of
Med, Seoul/Korea, Republic of, 7 Department of Oncology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul/Korea, Republic of, 8 Novartis
Pharmaceutical Corporation, East Hanover/NJ/United States of America, 9 Novartis
Pharma Ag, Basel/Switzerland, 10 Novartis Pharmaceutical Corporation, East
Hanover/United States of America, 11 Medical Oncology, Yonsei Cancer Center,
Seoul/Korea, Republic of
Background: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is
approved at 750 mg fasted for the treatment of patients with ALK-rearranged
(ALK+) metastatic non-small cell lung cancer (NSCLC) pretreated with
crizotinib. The pharmacokinetic (PK) part of this study (Part 1) compares
PK exposure of ceritinib following food consumption versus a fasted state
in advanced ALK+ NSCLC patients. Methods: Part 1 of this prospective,
open-label, multicenter, randomized, 3-arm, phase 1 study (ASCEND-8;
NCT02299505) is investigating PK and safety of ceritinib in advanced
ALK+ NSCLC patients, treatment-naïve or pretreated with multiple lines
of chemotherapy and/or crizotinib. Here, we compare steady-state PK of
ceritinib 450 or 600 mg taken with a lowfat meal versus ceritinib 750 mg
fasted (primary endpoint) and report preliminary safety outcomes from Part
1. Part 2 continues to randomize treatment-naïve patients and will assess
safety and efficacy. Results: As of June 16, 2016 (data cut-off), 137 patients
were randomized in a 1:1:1 ratio to each treatment arm; 135 patients received
one dose (safety set) and 97 patients had evaluable steady-state PK data.
Disease characteristics were comparable between arms. Median follow-up
duration was 4.14 months (range, 0.1–13.9). Relative to 750 mg fasted, the 450
mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed
arm showed ~25% higher steady-state PK (Table). Preliminary safety data
suggests overall frequency of AEs and types of AEs were comparable between
arms. However, incidences of gastrointestinal (GI)-related AEs (diarrhea,
nausea or vomiting) were lowest, with no grade 3/4 GI AEs reported, in the 450
mg fed arm.
P3.02B-001 PHASE 1 DOSE ESCALATION OF PF-06747775 (EGFR-
T790M INHIBITOR) IN PATIENTS WITH ADVANCED EGFRM (DEL 19
OR L858R+/-T790M) NSCLC
Hatim Husain 1 , Renato Martins 2 , Sarah Goldberg 3 , Peggy Senico 4 , Wendy
Ma 5 , Joanna Masters 6 , Nuzhat Pathan 6 , Dong-Wan Kim 7 , Mark Socinski 8 ,
Zelanna Goldberg 6 , Byoung Chul Cho 9
1 Medical Oncology, Uc San Diego Moores Cancer Center, La Jolla/CA/United States
of America, 2 Seattle Cancer Care Alliance, Seattle/WA/United States of America,
3 Medical Oncology, Yale Cancer Center, New Haven/CT/United States of America,
4 Pfizer Inc, Collegeville/PA/United States of America, 5 Pfizer New York, New York/
NY/United States of America, 6 Pfizer Inc, La Jolla/CA/United States of America,
7 Department of Internal Medicine, Seoul National University Hospital, Seoul/
Korea, Republic of, 8 University of Pittsburgh Medical Center, Hillman Cancer Center,
Pittsburgh/PA/United States of America, 9 Yonsei Cancer Center, Yonsei University
College of Medicine, Seoul/Korea, Republic of
Background: PF-06747775 (PF-7775) is a highly potent, selective third
generation irreversible EGFR-TKI, effective against EGFR-TKI sensitizing and
resistance (T790M) mutations in NSCLC cell lines; IC50s between 3-12 nM and
26X greater selectivity toward mutant vs. wild-type (WT)EGFR. This is the
first report from an ongoing phase I, first in human multicenter study
(NCT02349633) of PF-7775 in patients with metastatic EGFRm+ NSCLC.
Methods: EGFRm+ NSCLC pts, with acquired resistance to EGFR-TKIs enrolled
into dose escalation cohorts of PF-7775, orally once daily, beginning at 25 mg.
Stable brain metastases were allowed. All pts were assessed for
pharmacokinetics (PK), response to therapy, and adverse events (AEs).
Prospective central T790M testing was optional for dose escalation cohorts,
but is required in subsequent expansion cohorts. Plasma samples were
collected from all patients for ctDNA analysis of EGFR mutations. Results:
Dose escalation is complete. 26 patients enrolled in 7 dose levels (25-600 mg):
58% female, mean age 63.5 years, Asian/Caucasian 61%/34%, 14/25 T790M+.
Dosing reached 600 mg and then was expanded at a lower dose for better long
term tolerability. RECIST responses were observed at all dose levels. BOR is PR
11(42.3%; 5 T790M+), stable disease 6(23.1%; 4 T790M+), PD 2(7.7%: 1 T790M+),
symptomatic deterioration 1(3.8%; 1 T790M+), and indeterminate 6(23.1%; 3
T790M+). The AE profile is very favorable as predicted from the large WT
margin. No DLTs were observed. Grade 3 AEs were noted at > 150 mg (diarrhea
{n=4, 15.4%} and skin toxicities {n=8, 30.8%}). Figure 1. Best Change from
Baseline in Tumor Size (%)
PK were generally dose-proportional at doses of 25-600 mg, with a median
apparent t 1/2
of 6 h (range 4-30). Conclusion: PF-7775 has demonstrated early
signals of clinical activity and is well tolerated in EGFRm+ NSCLC pts with
acquired resistance to EGFR-TKIs.
Keywords: EGFRm NSCLC, T790M, Targeted therapy, 3rd generation EGFR TKI
S622 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017