Annual Meeting Proceedings Part 1 - American Society of Clinical ...

TPS7611 General Poster Session (Board #53E), Sat, 1:15 PM-5:15 PM
CA184-104: Randomized, multicenter, double-blind, phase III trial comparing
the efficacy of ipilimumab (Ipi) with paclitaxel/carboplatin (PC)
versus placebo with PC in patients (pts) with stage IV/recurrent non-small
cell lung cancer (NSCLC) of squamous histology. Presenting Author: Martin
Reck, Hospital Großhansdorf, Großhansdorf, Germany
Background: Years of research in advanced NSCLC have not improved
outcomes for the squamous subtype beyond those of standard platinum
doublets. Evidence of responses to immune therapies in NSCLC of
squamous cell histology supports investigation in this subtype. Ipi, a fully
human monoclonal antibody which blocks CTLA-4, augments antitumor
immune responses. Ipi improved overall survival (OS) in advanced melanoma,
with side effects managed using product-specific treatment guidelines;
immune-related response criteria (irRC) were derived from WHO
criteria to better capture response patterns observed with Ipi. A randomized
Phase 2 study of Ipi/PC in Stage IV NSCLC pts showed significant
improvement in progression-free survival (PFS), as measured by mWHO or
irRC, with a trend toward improved OS, over chemotherapy alone in pts
receiving phased Ipi/PC (Ipi started after 2 cycles of PC). Phased Ipi/PC
appeared to show efficacy in tumors of squamous histology. Addition of Ipi
did not exacerbate PC toxicity, and immune-related adverse events were
managed using protocol-specific guidelines. A Phase 3 trial (ClinicalTrials-
.gov identifier NCT01285609) is examining whether phased Ipi/PC will
prolong OS in chemotherapy-naïve pts with squamous NSCLC. Methods:
Stage IV/recurrent squamous NSCLC with ECOG 0-1 will be included; pts
with CNS metastases or history of autoimmune disease will be excluded.
Pts are randomized to receive 2 cycles of PC (175 mg/m2 and AUC�6,
respectively; IV), followed by 4 cycles of study drug (Ipi in Arm A, placebo in
Arm B; IV) with 4 additional cycles of PC (total 6 cycles). Pts without
progressive disease (PD) after induction receive maintenance therapy with
blinded study drug Q12W until PD per mWHO. The study will randomize
920 pts 1:1 between arms. The primary endpoint of this study is OS;
secondary endpoints include OS among pts who receive blinded therapy,
PFS and best overall response rate.
TPS7613^ General Poster Session (Board #53G), Sat, 1:15 PM-5:15 PM
The GALAXY Trial (NCT01348126): A randomized IIB/III study of
ganetespib (STA-9090) in combination with docetaxel versus docetaxel
alone in subjects with stage IIIB or IV NSCLC. Presenting Author: Glenwood
D. Goss, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada
Background: Hsp90 is a molecular chaperone required for proper folding
and activation of many cancer-promoting proteins and is recognized as a
key facilitator of cancer cell growth and survival. In pre-clinical models,
Hsp90 inhibition causes degradation of multiple client proteins and leads
to cancer cell death. Ganetespib is a resorcinolic Hsp90 inhibitor that has
shown potent anti-tumor activity in patients with lung, breast, and other
cancers that had progressed on standard treatment agents. Moreover,
combination of ganetespib with docetaxel results in synergistic antiproliferative
effects in several human non-small cell lung carcinoma (NSCLC)
tumor xenografts. Ganetespib is well tolerated and is devoid of severe liver
or common ocular toxicities that have been observed with some other
Hsp90 inhibitors. Diarrhea is the most common adverse event and is
manageable with appropriate supportive care. In a recent report, ganetespib
administered at 200 mg/m2 weekly showed activity in pretreated patients
with advanced NSCLC patients with ELM4-ALK translocation and KRAS
mutations. Methods: Stage 1 (240 subjects): randomized, international
open-label Phase 2B study in subjects that progressed on or after one prior
systemic therapy for stage IIIB or IV NSCLC: patients are prospectively
stratified for ECOG performance status, histology, total LDH, interval since
diagnosis, and smoking status. Co-primary endpoints are PFS in the ITT
population, and PFS in patients with KRAS mutations. Main secondary
endpoints include ORR, disease control rate, OS and clinical activity in
different molecular subtypes, including BRAF, HER2, EGFR, EML4-ALK.
Patients on the control arm are treated with docetaxel 75 mg/m2 on day 1 of
a three-week cycle. In the combination arm, ganetespib 150 mg/m2 is
given on day 1 (with docetaxel) and day 15 of a three-week cycle. At the
time of submission 90 subjects had been enrolled in Stage 1.
Lung Cancer—Non-small Cell Metastatic
507s
TPS7612 General Poster Session (Board #53F), Sat, 1:15 PM-5:15 PM
AvaALL: Open-label randomized phase IIIb trial evaluating the efficacy and
safety of standard of care with or without continuous bevacizumab (BV)
treatment beyond disease progression in patients (pts) with advanced
nonsquamous non-small cell lung cancer (NSCLC) after first-line (1L)
treatment with BV plus platinum-doublet chemotherapy (CT). Presenting
Author: Cesare Gridelli, SG Moscati Hospital, Avellino, Italy
Background: Pts with NSCLC have a poor prognosis upon progression
following 1L CT. Although the disease may have progressed on 1L CT, it is
likely still dependent on VEGF-mediated pathways. Thus, persistent VEGF
suppression along with second- and third-line cytotoxic regimens may yield
clinical benefit. Analyses have associated this strategy with improved
survival in NSCLC (Nadler et al, Oncologist 2011) and mCRC (Grothey et al
JCO 2008). Methods: AvaALL (MO22097; NCT01351415), a multicenter
(144 centers, 20 countries) open-label randomized (1:1) 2-arm phase IIIb
study, recruits pts with advanced non-squamous NSCLC that has progressed
after 1L treatment with BV plus a platinum-doublet and at least 2
cycles of BV maintenance monotherapy. Pts in the experimental arm
receive BV at the same dose from induction (7.5 or 15 mg/kg IV on D1 of
every 21-day cycle) continuously along subsequent lines, plus investigator’s
choice of second-line agent (limited to pemetrexed, docetaxel, or
erlotinib) and subsequent lines of treatment. Pts in the control arm receive
investigator’s choice of agent alone in second and subsequent lines of
treatment, but no further BV treatment. Stratifications include nature of
second-line standard treatment, number of cycles of BV maintenance (�6
vs. �6) and smoking status. The primary endpoint is overall survival (OS).
Secondary endpoints include 6-, 12-, and 18-month OS rates, progressionfree
survival, time to progression at second and third progressive disease
(PD), response rate, disease control rate, duration of response at second
and third PD, and safety of BV across multiple lines of treatment.
Exploratory objectives include quality of life assessment through multiple
treatment lines, and biomarker analysis. Assuming a median OS beyond PD
of 7.9 months in the control group and 10.1 months in the treatment arm
(HR 0.78), 528 events are required to achieve 80% power for the log-rank
test at a 2-sided significance level of 5%. Enrollment began in June 2011.
TPS7614 General Poster Session (Board #53H), Sat, 1:15 PM-5:15 PM
ASPIRATION: Phase II study of continued erlotinib beyond RECIST
progression in Asian patients (pts) with epidermal growth factor receptor
(EGFR) mutation-positive non-small cell lung cancer (NSCLC). Presenting
Author: Keunchil Park, Samsung Medical Center, Seoul, South Korea
Background: First-line erlotinib (an EGFR tyrosine-kinase inhibitor) significantly
increased progression-free survival (PFS) vs chemotherapy in phase
III trials of pts with EGFR mutation-positive NSCLC. Discontinuation of
erlotinib on RECIST disease progression (PD) may lead to rapid disease
flare-up; continued erlotinib beyond RECIST PD may extend clinical benefit
by slowing progression of this life-threatening disease. We describe
ASPIRATION, a large, Asian, multicenter, single-arm, open-label, phase II
trial (NCT01310036), which will increase understanding of first-line
erlotinib and erlotinib continuation beyond RECIST PD in pts with
EGFR-mutated NSCLC. Methods: Pts (n�204) �18 yrs with stage IV/
recurrent NSCLC, �1 measurable lesion (�10mm), ECOG performance
status (PS) 0-2 and positive EGFR mutation status established by local
pathology laboratory (that underwent voluntarily QA/QC) are eligible. All pts
receive erlotinib 150mg/day. Tumor response is evaluated using RECIST
(v1.1). The primary endpoint is PFS. At investigator’s discretion, pts may
continue on erlotinib beyond RECIST PD, e.g. if they have slow PD (�6
months of partial response/stable disease), asymptomatic minimal PD, or
new brain metastasis controlled locally. Pts should not continue erlotinib if
they have extracranial PD with symptoms; rapid PD and/or worsening of PS;
or life-threatening complications. Pts continuing erlotinib who present with
second RECIST PD will discontinue. Secondary endpoints include objective
response rate, disease control rate, overall survival, and safety. For the
exploratory biomarker study, pre-treatment tumor tissue blocks are collected;
remaining tissue (after EGFR mutation testing for eligibility) will be
analyzed centrally to study the association of biomarkers and clinical
outcomes. Pre-treatment and post-treatment plasma and serum samples
will be obtained at various time points for biomarker assays, including
EGFR mutations and other candidate NSCLC biomarkers. Recruitment
began in Apr 2011; the estimated final data collection for the primary
endpoint is Dec 2014.
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