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

TPS3637 General Poster Session (Board #39B), Mon, 8:00 AM-12:00 PM
The GAIN-C study (BP25438): Randomized phase II trial of RG7160
(GA201) plus FOLFIRI, compared to cetuximab plus FOLFIRI or FOLFIRI
alone in second-line KRAS wild type (WT) or mutant metastatic colorectal
cancer (mCRC). Presenting Author: Andres Cervantes-Ruiperez, Department
of Hematology and Medical Oncology, INCLIVA, University of Valencia,
Valencia, Spain
Background: GA201 is a novel, dual-acting, humanized, glycoengineered
IgG1 anti-EGFR monoclonal antibody, with enhanced antibody-dependent
cellular cytotoxicity (ADCC) activity in combination with signal inhibition.
GA201 demonstrates significantly enhanced in vitro/vivo activity compared
to cetuximab (cet) both as a single agent and in combination with
irinotecan, in both KRAS mutant and BRAF mutant models and promising
clinical activity in ph I and neo-adjuvant trials (Paz Ares et al, JCO 2011)
including KRAS mutant mCRC. A randomized ph II program was launched:
one study in NSCLC and GAIN-C in mCRC (NCT01326000), which is
presented here. Methods: Main inclusion criteria are progression on 1L
containing oxaliplatin, ECOG 0-1, and adequate hematological and liver
function. Main exclusion criteria: prior anti-EGFR treatment. A total of 160
patients in 2L mCRC (stratified for EGFR expression, disease progression
before or after 6 months after starting 1L, prior treatment with bevacizumab
Y vs N) will be randomized to receive either GA201 (day 1, 8 of cycle
1 then q2W) or cet (qW) � FOLFIRI q2W (KRAS WT) or to receive GA201�
FOLFIRI or FOLFIRI alone (KRAS mutant). Collection of archival tumor
plus a mandatory fresh tumor biopsy at baseline were implemented
because ph I data showed that EGFR expression is not concordant between
the two specimen types and to optimize assessment of potential immune
related biomarkers. The fresh tumor biopsy will be centrally analyzed for
EGFR (immunohistochemistry) and KRAS status. Primary objective is
progression free survival; secondary endpoints are to define objective
response rates, the safety profile, pharmacokinetics and pharmacodynamics.
A comprehensive biomarker program (blood and tumor), mainly
immune-phenotyping, immunohistochemistry in tumor samples (Ventana)
and immune functional tests (including adaptive responses) were set up to
investigate potential predictive biomarkers and the mode of action of
GA201. Study is ongoing worldwide in 9 countries with the safety run-in
phase completed in Nov 2011. Recruitment is planned to be completed by
end of April 2012.
TPS3639 General Poster Session (Board #39D), Mon, 8:00 AM-12:00 PM
Sequential first-line treatment for metastatic colorectal cancer with capecitabine,
irinotecan, and bevacizumab: Capecitabine plus bevacizumab
(Cape-Bev) versus capecitabine, irinotecan plus bevacizumab (CAPIRI-
Bev): The AIO KRK 0110/ML22011 randomized, phase III trial. Presenting
Author: Clemens Albrecht Giessen, Department of Hematology and Oncology,
Klinikum Grosshadern and Comprehensive Cancer Center, LMU
Munich, Munich, Germany
Background: Several randomized trials have indicated that combination
chemotherapy applied in metastatic colorectal cancer (mCRC) does not
significantly improve overall survival when compared to the sequential use
of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present
study investigates the question in bevacizumab-based first-line treatment
including escalation- and de-escalation strategies. Methods: The AIO KRK
0110/ML22011 trial (ClinicalTrials.gov NCT01249638) is a two-arm,
multicenter, open-label randomized phase III trial comparing the efficacy
and safety of Cape-Bev versus CAPIRI-Bev in the first-line treatment of
metastatic colorectal cancer. Patients with unresectable metastatic colorectal
cancer, ECOG PS 0-1, will be assigned in a 1:1 ratio to receive either
capecitabine 1250 mg/m2 bid for 14d (d1-14) plus bevacizumab 7.5
mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m2 BID for 14d (d1-14),
irinotecan 200 mg/m2 (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B).
Patients included into this trial are required to consent to the analysis of
tumor tissue and blood for translational investigations. In Arm A, treatment
escalation from Cape-Bev to CAPIRI-Bev is recommended in case of
progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to
Cape-Bev is possible after 6 months of treatment or in case of irinotecanassociated
toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The
primary endpoint is time to failure of strategy (TFS). Secondary endpoints
are ORR, OS, PFS, safety and quality of life. Conclusion: The AIO KRK
0110 trial is designed for patients with disseminated, but asymptomatic
mCRC who are not potential candidates for surgical resection of metastasis.
Two bevacizumab-based strategies are compared: one starting as singleagent
chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and
another starting with CAPIRI-Bev and allowing de-escalation to Cape-Bev
and subsequent re-escalation if necessary. By January 2012, 79 of
planned 516 patients have been enrolled.
Gastrointestinal (Colorectal) Cancer
237s
TPS3638 General Poster Session (Board #39C), Mon, 8:00 AM-12:00 PM
A pilot trial of a combination of therapeutic vaccines (GI-4000 and
GI-6207) as adjunctive therapy with first-line therapy with bevacizumab
plus either FOLFOX or FOLFIRI in stage IV patients with newly diagnosed
Ras-mutant positive or negative metastatic colorectal cancer. Presenting
Author: John Marshall, Lombardi Comprehensive Cancer Center, Georgetown
University, Washington, DC
Background: A promising approach for the treatment of cancer is the
development of vaccines that target specific tumor antigens. In the
metastatic CRC patient population, targeted and active immunotherapy
may inhibit cancer progression and improve survival. This trial is designed
to evaluate the efficacy, immunogenicity, and safety of GI-4000 plus
standard therapy in patients with metastatic colorectal cancer. GI-4000 is
a proprietary immunotherapy that uses whole, heat-killed recombinant
Saccharomyces cerevisiae yeast (called Tarmogens � Targeted Molecular
Immunogens). GI-4000 is designed to activate a cellular immune response
to target cells with activating ras mutations. Tarmogens have been shown to
elicit selective killing of target cells that express a number of cancer
antigens, including mutated Ras, by activation of antigenspecific T cell
mediated responses. Methods: The study population consists of subjects
with metastatic colorectal cancer with an activating mutation in ras. Newly
diagnosed subjects receive FOLFOX (or FOLFIRI) � bevacizumab (Bev) �
GI- 4000; 3 weekly injections of GI-4000 are followed by 8 cycles of Bev �
FOLFOX (or FOLFIRI); day 1 and 2 every 14 days. Doses of GI-4000 are
administered on day 8 of each cycle. Upon completion of chemotherapy,
GI-4000 continues along with Bev maintenance every 2 weeks for up to 5
years or until subjects experience intolerance, disease recurrence, or death.
If Bev is stopped, GI-4000 may continue on the same maintenance
schedule alone. Subjects that have already completed standard chemotherapy
(FOLFOX or FOLFIRI) may enter the study and receive Bev �
GI-4000 every 2 weeks for up to 5 years. Enrollment is ongoing and will
continue up to 52 subjects.
TPS3640 General Poster Session (Board #39E), Mon, 8:00 AM-12:00 PM
A randomized, phase II, multicenter, double-blind, placebo-controlled
study evaluating onartuzumab (MetMAb) in combination with mFOLFOX6
plus bevacizumab in patients with metastatic colorectal cancer. Presenting
Author: Johanna C. Bendell, Sarah Cannon Research Institute, Nashville,
TN
Background: Dysregulation of the HGF/Met (Met) pathway has been linked
with poor prognosis in colorectal cancer. Crosstalk between the Met and
vascular endothelial growth factor (VEGF) pathways may be important
during tumorigenesis. Aberrant activation of the HGF/Met pathway may
promote angiogenesis via tumor cell secretion of angiogenic factors or
directly activating endothelial cells. Onartuzumab (MetMAb) is a monovalent,
monoclonal antibody that specifically binds to the Met receptor. The
combination of onartuzumab and VEGF inhibition in preclinical models
resulted in enhanced antitumor activity over either treatment alone.
Preclinical efficacy data support the combination of onartuzumab with
platinum agents. In phase I studies, onartuzumab has been generally well
tolerated alone and in combination with bevacizumab. Adverse events most
commonly associated with onartuzumab are peripheral edema and fatigue.
Methods: This is a randomized, two-arm, phase II study in patients with
previously untreated metastatic colorectal cancer. Patients (n�188) will
be randomized (1:1) to either mFOLFOX6/bevacizumab/placebo or mFOL-
FOX6/bevacizumab/onartuzumab. Oxaliplatin will be discontinued after 8
cycles with remaining drugs continued until progression. The primary
endpoint of this study is PFS in all patients. PFS by Met IHC diagnostic
status (Met positive vs Met negative) will also be analyzed. Secondary
endpoints include OS, ORR, safety, and biomarker analyses. Primary and
secondary analyses will include all randomized patients and will be
conducted according to assigned treatment arm. Kaplan–Meier methodology
will be used to estimate median PFS for each treatment arm. An
estimate of HR with 95% CI will be determined using a Cox regression
model. Safety will be assessed in all patients receiving at least one dose of
any treatment. This study is open for accrual; further details can be found
on ClinicalTrials.gov (NCT01418222).
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