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Olaratumab imc 3 g3 ottobre 2010
1. www.esanum.it/cool
The Platelet-Derived Growth Factor (PDGF)
Family of Ligands and Receptors, and PDGFRα Signaling Pathways
Östman A, Heldin C-H. Adv Cancer Res. 2007;97:247-274; Loizos N et al. Mol Cancer Ther. 2005;4:369-379; Schmitt J, Matei D. Clin Ovarian
Cancer. 2008;1:120-126;Imclone Systems, Data on File.
PDGFRa is overexpressed in multiple tumor types, including lung, with
expression being associated to aggressive phenotypes and increased
metastasis
PDGFRα is expressed in both tumor and stromal cells
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Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal
antibody targeted against platelet-derived growth factor receptor-α (PDGFRα)
Loizos N et al. Mol Cancer Ther. 2005;4:369-379; ImClone Systems. Data on file; Matei D et al. Oncogene 2006;25:2060-2069; Youssoufian H et al. J Clin Oncol.
2008;26:15s. Abstract 14617; Östman A, Heldin C-H. Adv Cancer Res. 2007;97:247-274; Schmitt J, Matei D. Clin Ovarian Cancer. 2008;1:120-126.
In preclinical studies:
Binds to PDGFRα with high
affinity; Kd=40 pM
Blocks receptor activation in tumor
and stromal cells
Inhibits activation of downstream
effector molecules
May cause anticancer activity by
directly inhibiting tumor growth
inhibiting angiogenesis and the
surrounding tumor milieu
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Studies of olaratumab in NSCLC
Ongoing trials
Study ID Ph Eligibility/Line Arm(s) N (projected)
NCT00918203 II Stage IIIB/IV, first line
Paclitaxel + Carboplatin
IMC-3G3 + Paclitaxel +
Carboplatin
136
www.clinicaltrials.gov (accessed on August 28th, 2010)
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A Randomized Phase 2 Study of IMC-3G3
With or Without Carboplatin and Paclitaxel in Patients With Previously
Untreated Locally Advanced or Metastatic NSCLC
• NSCLC stage IIIB or IV
• No prior chemotherapy
or targeted therapy in
the metastatic setting
• Squamous histology
eligible
• CNS metastases
allowed
• Age ≥18
• ECOG performance
status ≤1
R
A
N
D
O
M
I
Z
E
IMC-3G3
IMC-3G3 15 mg/kg
day 1, 8
+
Taxol 200 mg/m2
day 1
+
Carboplatin AUC=6 day 1
every 3 weeks x 6
Paclitaxel 200 mg/m2
day 1
+
Carboplatin AUC=6 day 1
every 3 weeks x 6
N=136
Primary Objective: PFS
www.clinicaltrials.gov; NCT00918203 (accessed on August 28th, 2010)
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